WO2024193965A1

WO2024193965A1 - Rsv-f-encoding nucleic acids

Info

Publication number: WO2024193965A1
Application number: PCT/EP2024/055127
Authority: WO
Inventors: Marco BIANCUCCI; Kambiz MOUSAVI; Nicholas John BARROWS; Xiaofeng Wang; Corey Mallett; Emily PHUNG
Original assignee: GlaxoSmithKline Biologicals SA
Current assignee: GlaxoSmithKline Biologicals SA
Priority date: 2023-03-17
Filing date: 2024-02-28
Publication date: 2024-09-26
Anticipated expiration: 2025-09-17

Abstract

The present disclosure provides inter alia, a recombinant nucleic acid encoding a respiratory syncytial virus fusion (RSV-F) protein comprising a cytoplasmic tail; wherein, relative to a cytoplasmic tail according to SEQ ID NO: 3 or 4, 2-20 residues are deleted from the cytoplasmic tail of the RSV-F protein.

Description

Docket No.: 70280WO01 RSV-F-ENCODING NUCLEIC ACIDS FIELD The present disclosure is in the field of vaccinology, in particular antigen design for nucleic acid-based vaccines. BACKGROUND Respiratory syncytial virus (“RSV”) is a ribonucleic acid virus of the Pneumoviridae family of which two antigenically distinct subgroups, referred to as RSV A and RSV B, exist. RSV is a leading cause of infant and older adult hospitalisation and mortality. Each year in the United States, RSV leads to approximately 58,000 hospitalisations with 100-500 deaths among children under five [1], and 177,000 hospitalisations with 14,000 deaths among adults aged 65 years and above [2]. The development of a safe and efficacious vaccine to prevent severe disease and hospitalization from RSV is therefore a high priority. The antiviral drug ribavirin is the only approved antiviral therapy for RSV treatment, but its use is restricted to severe hospitalized cases in infants and young children [3]. Furthermore, two RSV- specific humanized monoclonal antibodies, palivizumab (Synagis) and motavizumab, are confirmed to be safe and effective in reducing RSV hospitalization rates and serious complications among high- risk children in multiple clinical settings [4, 5, 6, 7, 8]. Available treatment for RSV in older adults is generally supportive in nature, consisting of supplemental oxygen, intravenous fluids and bronchodilators. In May 2023, the first RSV vaccine was approved by the FDA (AREXVY, for older adults). However, there evidently remains a need for further safe and effective prophylactic vaccines against RSV. The RSV fusion protein (“RSV-F”) in the viral envelope is the most effective target of neutralising antibodies, such as motavizumab. Recent advances in RSV-F structural biology have revealed changes in its antigenic characteristics that occur during the fusion process between the viral envelope and host cell membrane. RSV-F adopts a metastable “pre-fusion” conformation in the viral envelope as a homotrimer, and then an irreversible and distinct “post-fusion” conformation during fusion with the host cell membrane (see Figure 2 of [9]). The trimeric pre-fusion conformation is more immunogenic, and is bound by most RSV-F-specific neutralising antibodies in human sera. To date, there remains a need for pre-fusion RSV-F antigen designs which can be expressed at high levels from nucleic acids (and thus may be encoded into a nucleic acid-based vaccine). SUMMARY The inventors have enhanced the cell-surface expression of trimeric, pre-fusion RSV-F protein when expressed from nucleic acids, e.g. through specific mutation of the protein’s C-terminal cytoplasmic Docket No.: 70280WO01 tail (CT). Such mutation involves the deletion of C-terminal residues from the CT, such as at least 3, at least 5, at least 10, at least 15, or at least 20 residues, as opposed to deletion of the entire CT. By way of example, as described in Example 2, both 3 and 20 C-terminal residues were deleted from the CT of four different RSV-F protein designs. Such deletion enhanced the in vitro cell-surface expression of trimeric pre-fusion RSV-F over a period of 96 hours for all antigen designs tested, compared to the corresponding RSV-F protein with both (i) a fully intact CT and (ii) the entire deletion of the CT (see e.g. Figure 2). In addition, by way of example, deletion of 5, 10 and 15 C-terminal residues also resulted in enhanced in vitro cell-surface expression of trimeric pre-fusion RSV-F protein, compared to the corresponding RSV-F protein with a fully intact CT (see, e.g. Example 5; Figure 5A and B). Surprisingly, deletion of 15, 16, 17 and 20 C-terminal residues resulted in higher trimeric pre-fusion RSV-F expression at 72 and 96 hours post-transfection, compared to the deletion of 21 C-terminal residues (see e.g. Example 12; Figure 19A). Furthermore, the positive effect of a 20 C-terminal residue deletion (as compared to a fully intact CT) was found to be consistent across a wide variety of RSV-F antigen designs (see e.g. Example 8; Figures 8-10), and was observed in different cell types (see e.g. Example 10; Figures 16 and 17). In the context of nucleic acid-based vaccines, enhanced cell-surface expression over time may allow for greater exposure of the immune system to the vaccine antigen. Moreover, in the case of RSV-F, its trimeric, pre-fusion conformation resembles the native structure of the protein in the viral envelope prior to host cell fusion. Therefore, expression in specifically this conformation (moreover, at high levels over extended periods of time) may be more immunogenic. Such in vitro observations are corroborated by in vivo evidence. By way of example (see e.g. Examples 6 and 13), RNA constructs encoding various RSV-F proteins with either a fully intact CT, or comprising the deletion of 20 C-terminal residues (“ΔCT20”), were used in murine immunisation studies. As shown in e.g. Figure 7B, at the lower of two different RNA doses tested, constructs comprising a ΔCT20 generally elicited higher neutralising antibody titres against e.g. RSV of the A subtype, in comparison to their counterparts with a fully intact CT. Example 13 (Figure 21) also demonstrates the positive effects of the ΔCT20 deletion on neutralising antibody titres against RSV strains of both the A and B subtypes (comparing constructs “647” and “647 ΔCT20”). Neutralising antibody titres generally correlate with inhibition of viral replication in the lungs and other respiratory sites, and thus protective efficacy in a subject. Hence, without wishing to be bound by theory, a mutated CT as disclosed herein may allow for protective efficacy against RSV to be achieved at lower doses of a nucleic acid-based vaccine, leading to further possible benefits, e.g. reduced reactogenicity. Protein subunit-based RSV vaccines are currently being pursued, for at least the older adult population [10], [11]. However, there are potential advantages to nucleic acid-based vaccines, such as avoiding Docket No.: 70280WO01 the risks of pre- to post-fusion conformational change of a protein subunit during storage and transportation. The modifications to the RSV-F protein disclosed herein may expand patient options to include nucleic acid-based vaccines which can elicit high and sustained antigen expression. Therefore, nucleic acids generated by the inventors (and proteins encoded thereby) may be useful, in particular in prophylactic vaccination against RSV. Accordingly, in a first independent aspect, the present disclosure provides: A recombinant nucleic acid encoding an RSV-F protein comprising a cytoplasmic tail; wherein, relative to a cytoplasmic tail according to SEQ ID NO: 3 or 4, 2-20 residues are deleted from the cytoplasmic tail of the RSV-F protein. The residues are preferably deleted from the C-terminal end of the cytoplasmic tail of the RSV-F protein. The nucleic acid is preferably RNA. In a further independent aspect, the present disclosure provides an RSV-F protein that is encoded by a nucleic acid of the present disclosure. In a further independent aspect, the present disclosure provides a host cell comprising a nucleic acid of the present disclosure. In a further independent aspect, the present disclosure provides a carrier (preferably, a lipid nanoparticle) comprising a nucleic acid of the present disclosure. In a further independent aspect, the present disclosure provides a pharmaceutical composition comprising a nucleic acid (preferably RNA), RSV-F protein or carrier (preferably lipid nanoparticle) of the present disclosure. In a further independent aspect, the present disclosure provides a nucleic acid (preferably RNA), RSV- F protein, carrier (preferably lipid nanoparticle) or pharmaceutical composition of the present disclosure, for use in medicine. In a further independent aspect, the present disclosure provides a therapeutic method comprising administering an effective amount of the nucleic acid (preferably RNA), RSV-F protein, carrier (preferably lipid nanoparticle), or pharmaceutical composition of the present disclosure to a subject. In an embodiment of said aspect, the present disclosure provides a method of inducing an immune response against RSV in a subject, the method comprising administering an effective amount of the RNA, carrier (preferably lipid nanoparticle) or pharmaceutical composition of the present disclosure to a subject. In a further independent aspect, the present disclosure provides an in vitro method for the production of an RSV-F protein of the present disclosure, comprising expressing a nucleic acid of the present disclosure (preferably, an expression vector) in a host cell. Docket No.: 70280WO01 Further exemplary independent aspects of the present disclosure are provided throughout the detailed description, below. DESCRIPTION OF FIGURES References to “CTD” (cytoplasmic tail domain) in the figures are equivalent to references to “CT” (cytoplasmic tail) throughout this specification. Accordingly, “CTDΔ20” is equivalent to “ΔCT20”, and so forth. Figure 1. Human primary BJ cells support surface expression of RSV F protein from candidate mRNAs. Representative images from a 4-day time course assay are shown. As shown, indirect immunofluorescence and imaging (10x objective) captures the individual cell nuclei (denoted ‘) and the cell surface RSV F (denoted “) variant F318 with 3 amino acids removed from the cytoplasmic tail (CT) in cells fixed approximately 8 (A’ & A”), 24 (B’ & B”), 48 (C’ & C”), 72 (D’ & D”) or 96 (E’ & E”) hours post transfection and labelled by using the primary antibody motavizumab. The population distribution from High Content imaging (HCi) and analysis for BJ cells transfected and labelled corresponding to the representative images in panels A-E is shown at approximately 8 (F), 24 (G), 48 (H), 72 (I) and 96 (J) hours post transfection. As representative of non-specific staining, a population distribution for BJ cells treated as above and fixed at 1 hour post transfection is shown in each (F-J) panel for reference. The population distribution was binned and plotted by GraphPad Prism using the cell-specific RSV F average intensity values from High Content Imaging (HCi) and analysis. Figure 2. Deletion of the RSV F CT increases cell-surface expression of the pre-fusion RSV F trimer. The cell-surface expression of RSV F trimer protein was evaluated by indirect immunofluorescent labelling using monoclonal antibody AM14 followed by quantification using high content imaging and analysis across a 4-day time course. Primary, human BJ cells were forward transfected in 96-microwell format with mRNAs encoding RSV F variants F(ii) (A), F318 (B), F319 (C) or F(i) (D) (solid dot, solid line) or the respective CT deletion variations CT Δ3 (solid dot, dashed line), ΔCT20(open circle, dashed line), or ΔCT (i.e. deletion of the entire CT - open circle, solid line). At specific time points (hours post transfection) cell monolayers are fixed, then RSV F was labelled and imaged using a 10x objective. For line graphs, each plotted value expresses the average intensity of the Alexa647 signal for cells identified by automated image analysis from 9 imaged fields per well. Each point on the line graph represents the mean (µ) +/- 1 standard deviation (σ) from 3 biological replicates. The area under the curve (AUC) for each line graph is shown (E) with 1 standard error of the mean (SEM). The means, AUC and variability shown on the line and bar graphs were calculated by GraphPad Prism software. Figure 3. Total expression of the RSV F protein increases for mRNA vaccine candidates with CT deletions. The cell-surface expression of RSV F protein was evaluated by indirect immunofluorescent labelling using the primary anti-RSV F antibody motavizumab followed by quantification using HCi and analysis across a 4-day time course. Primary, human BJ cells were forward transfected in 96- microwell format with mRNAs encoding RSV F variants F(ii) (A), F318 (B), F319 (C) or F(i) (D) Docket No.: 70280WO01 (solid dot, solid line) or the respective CT deletion variations CT Δ3 (solid dot, dashed line), ΔCT20(open circle, dashed line), or ΔCT (open circle, solid line). At specific time points (hours post transfection) fixation of cell monolayers was followed by labelling and imaging using a 10x objective. For line graphs, each plotted value expresses the average intensity of the Alexa647 signal for cells identified by automated image analysis from 9 imaged fields per well. Each point on the line graph represents the mean (µ) +/- 1 standard deviation (σ) from 3 biological replicates. The area under the curve (AUC) for each line graph is shown (E) with 1 standard error of the mean (SEM). The means, AUC and variability shown on the line and bar graphs were calculated by GraphPad Prism software. Figure 4. In vitro validation of mRNAs for in vivo study. Select mRNAs encoding RSV F were forward transfected into primary BJ cell monolayers. The cell monolayers were fixed and RSV F protein expression was evaluated by indirect immunofluorescence coupled with HCi and image analysis. The mRNAs encode RSV F variants including DS-CAV1, F(ii), F(iii) and F(i) proteins or the F318 and F319 protein constructs. Results for corresponding variants lacking the CT 20 amino acids (ΔCT20) are also shown. RSV F surface protein expression was quantified 1 day post infection by labelling cells using the anti-RSV F antibodies Motavizumab (A), D25 (E) or AM14 (I) or 3 days post transfection (Motavizumab (C), D25 (G) or AM14 (K)). The average cell count for three imaged wells is shown and corresponds to the RSV F expression values for 1 day post infection (Motavizumab (B), D25 (F) or AM14 (J) or 3 days post transfection (motavizumab (D), D25 (H) or AM14 (L)). Each graph depicts the mean (µ) +/- 1 standard deviation (σ) from 3 biological replicates as calculated by GraphPad Prism software. Figure 5. A short, 5 amino acid CT (See Table 2, Row 6) for RSV F protein maximally enhanced RSV F protein expression both within the cell and at the cell surface. In vitro transcribed mRNAs that encoded variations of F(ii) CT lengths (0, 5, 10, 15, 20, 22 amino acids & full length) were forward transfected into primary, BJ cell monolayers. The cell monolayers were fixed at time points either 20 or 47 hours post transfection. Surface exposed, trimeric RSV F (Figure 5A) or whole-cell, prefusion RSV F (Figure 5B) was quantified by High Content imaging following immunolabeling of the fixed BJ cells. Trimeric pre-fusion RSV F (identified by AM14), or prefusion F (identified by D25), was quantified. Each graph depicts the mean (µ) +/- 1 standard deviation (σ) from 3 biological replicates as calculated by GraphPad Prism software. Background staining represents the median value from 6 wells processed simultaneously as the experimental non-transfected wells. Figure 6. RSV pre-F IgG binding antibody geometric mean titres on day 21 (3wp1) and day 35 (2wp2) in animals immunized with (A) 2 μg or (B) 0.2 μg of RNA encoding F(iii), F(i), F(i) ΔCT20, F(ii), F(ii) ΔCT20, DS-Cav1, F318, F318 ΔCT20, F319, or F319 ΔCT20 (where each point represents an individual animal). Statistical comparisons of constructs (GMR with 90% CI) are presented in (C)-(G). Figure 7. RSV A neutralising antibody titres (ED60) on day 21 (3wp1) and day 35 (2wp2) in animals immunized with either (A) 2 μg or (B) 0.2 μg of RNA encoding F(iii), F(i), F(i) ΔCT20, F(ii), F(ii) Docket No.: 70280WO01 ΔCT20, DS-Cav1, F318, F318 ΔCT20, F319, or F319 ΔCT20 (where each point represents an individual animal). Statistical comparisons of constructs (GMR with 90% CI) are presented in (C)-(E). Figure 8. 26 RSV F-encoding mRNAs were screened in primary human BJ cells for their ability to express the RSV F antigen on the cell surface. RSV F trimeric surface expression was detected by indirect immunofluorescent labelling (using AM14 antibody) followed by quantification using high content imaging and analysis. At (A) 25 hours, and (B) 72 hours post-transfection (hpt) cell monolayers were fixed, then RSV-F was labelled and imaged using a 10x objective. Each bar depicts the average intensity of the Alexa647 signal for cells identified by automated image analysis from 9 imaged fields per well, and as shown, represents the mean (µ) +/- 1 standard deviation (σ) from 3 biological replicates, as calculated by GRAPHPAD PRISM software. Figure 9. 26 RSV F-encoding mRNAs were screened in primary human BJ cells for their ability to express the RSV F antigen on the cell surface. RSV F pre-fusion surface expression was detected by indirect immunofluorescent labelling (using D25 antibody) followed by quantification using high content imaging and analysis. At (A) 25 hours, and (B) 72 hours post-transfection (hpt) cell monolayers are fixed, then RSV-F was labelled and imaged using a 10x objective. Each bar depicts the average intensity of the Alexa647 signal, as per Figure 16. Figure 10. 26 RSV F-encoding mRNAs were screened in primary human BJ cells for their ability to express the RSV F antigen on the cell surface. Total RSV F surface (pre- or post-fusion conformation) expression was detected by indirect immunofluorescent labelling (using motavizumab antibody) followed by quantification using high content imaging and analysis. At (A) 25 hours, and (B) 72 hours post-transfection (hpt) cell monolayers are fixed, then RSV-F was labelled and imaged using a 10x objective. Each bar depicts the average intensity of the Alexa647 signal, as per Figures 16 and 17. Figure 11. Zoomed in view of substitution 228K from cryo-EM structure of a parental design to inter alia, F217, F528 and F647, called F21 (structure as depicted here also applicable to aforementioned designs). K228 and surrounding residues are depicted as sticks. Hydrogen bond between K228 and Y250 is depicted as a dashed line. Figure 12. Zoomed in view of substitution 55T from cryo-EM structure of a parental design to inter alia, F217, F528 and F647, called F21 (structure as depicted here also applicable to aforementioned designs). T55 is shown as sticks with a transparent surface. Residues forming the hydrophobic pocket and involved in van der Waals contacts with T55 are shown as sticks (including hydrophobic pocket). Figure 13. Zoomed in view of substitution 215A from cryo-EM structure of a parental design to inter alia, F217, F528 and F647, called F21 (structure as depicted here also applicable to aforementioned designs), including proximal α helices. A215 is depicted as stick with transparent surface. Residues forming a hydrophobic region that may be involved in van der Waals contacts with A215 are shown as sticks. Docket No.: 70280WO01 Figure 14. (A) Protein yields minimal substitution designs, relative to DS-Cav1. Negative control (EXPIFECTAMINE and cell culture supernatant), F225 (positive control; SEQ ID NO: 77) and F300 (wild-type) also shown. Figure 15. Octet BLI of the minimal substitution designs bound to RSV-F antibodies (AM14, D25, RSB1, motavizumab), relative to DS-Cav1. Negative control (EXPIFECTAMINE and cell culture supernatant), F225 and F300 (wild-type) also shown. Figure 16. Protein expression of RSV F in human skeletal muscle cells increased with ΔCT20 deletion. Primary human skeleton muscle cells (three donors) were transfected with mRNA using LIPOFECTAMINE3000 for 24 hours. Plot represents area under the curve (AUC) for integrated mean fluorescent average intensity (iMFI) of F(ii) parental protein (KM135) vs F(ii) ΔCT20 (KM140). Each dot represents three technical replicates. Bars indicate the mean of the three experiments. Figure 17. Protein expression of RSV F in dendritic cells increased with ΔCT20 deletion. Dendritic cells were transfected with mRNA using LIPOFECTAMINE3000 for 24 hours. (A) AUC for integrated iMFI of F(ii) parental protein (KM135) vs F(ii) ΔCT20 (KM140). B. AUC for integrated iMFI for F647 and F647 ΔCT20 with and without mRNA codon optimization (two donors). Each dot represents three technical replicates. Bars indicate the mean. Figure 18. 7 RSV F-encoding mRNAs with different numbers of substitutions were screened in primary human BJ cells for their ability to express AM14-positive RSV-F antigen (see Table 8 for encoded proteins). Each bar depicts the average intensity of the Alexa647 signal for cells identified by automated image analysis from 9 imaged fields per well, and as shown, represents the mean (µ) +/- 1 standard deviation (σ) from 3 technical replicates, as calculated by GraphPad Prism software. Figure 19. The optimal length of the RSV F CT that supports cell-surface expression of the trimeric, pre-fusion RSV F protein includes CTs of at least 5, but not longer than 10, amino acids. The cell- surface expression of trimeric, pre-fusion RSV F protein was evaluated by indirect immunofluorescent labelling using monoclonal antibody AM14 followed by quantification using high content imaging and analysis across a 4-day time course. Primary, human fibroblast (BJ) cells were forward transfected in 96-well format with mRNAs encoding RSV F variant F(ii). In (A), select CT variations are shown. The parent (F(ii), solid line, solid box) was modified by deletion of the RNA sequence encoding the terminal 15 amino acids (F(ii) CTDΔ15, solid line, solid circle), 16 amino acids ((F(ii) CTDΔ16, dotted line, solid circle), 17 amino acids (F(ii) CTDΔ17, dotted line, open circle), 20 amino acids (F(ii) CTDΔ20, solid line, open circle), 21 amino acids (F(ii) CTDΔ21, dotted line, solid box), or complete deletion of the CT domain (F(ii) CTDΔ25, solid line, open box). In (B), the area under the curve is shown, as calculated from the line graphs in (A) and extended to include additional CT deletions, and (C), the same data as B depicted as line graph. At specific time points (hours post transfection) cell monolayers were fixed, then RSV F was labelled and imaged using a 10x objective. For line graphs, Docket No.: 70280WO01 each plotted value expresses the average intensity of the Alexa647 signal for cells identified by automated image analysis from 9 imaged fields per well. Each point on the line graph represents the mean (µ) +/- 1 standard deviation (σ) from 3 biological replicates. The area under the curve (AUC) is shown in (B) with 1 standard error of the mean (SEM). The means, AUC and variability shown on the line and bar graphs were calculated by GraphPad Prism software. Figure 20. As for Figure 19 but with D25 antibody binding being assessed. Figure 21. (A) RSV A neutralising antibody titres (ED60) on day 21 (3wp1) and day 35 (2wp2) in animals immunized with 0.5 μg of F528, F647, F647 ΔCT20, F651 ΔCT20, F(iii), F(i), F(ii), or DS- Cav1 (where each point represents an individual animal). (B) RSV A and B day 35 (2wp2) cross- neutralisation titres to lab-adapted (RSV A-long and RSV B-18537) and clinical RSV strains (RSV A- Clinical 2015, RSV B-Clinical 2015 and 2017). Figure 22. (A) pre-F and (B) post-F IgG binding antibody titres on day 21 and day 35 for constructs in Example 13. Figure 23. HPLC chromatograms assessing monodispersity of F310 or F310_v2 (2x Strep tag removed relative to F310) following purification, incubation at 4°C overnight, or one freeze/thaw cycle. DETAILED DESCRIPTION Nucleic acids encoding RSV-F proteins comprising deletions in the cytoplasmic tail The present disclosure provides, in an independent aspect, a recombinant nucleic acid encoding an RSV-F protein comprising a cytoplasmic tail; wherein, relative to cytoplasmic tail according to SEQ ID NO: 3 or 4, 2-20 residues are deleted from the cytoplasmic tail of the RSV-F protein (preferably from the C-terminal end thereof). A further independent aspect of the present disclosure provides a recombinant nucleic acid encoding an RSV-F protein comprising a cytoplasmic tail; wherein the cytoplasmic tail is 2-23 residues in length. For the avoidance of doubt, such recombinant nucleic acids, and the RSV-F proteins which they encode, are respectively referred to herein as “nucleic acids of the present disclosure” and “RSV-F proteins of the present disclosure”. The wild-type RSV-F sequences of SEQ ID NO: 1 (A2 subtype) and SEQ ID NO: 2 (B subtype strain 18537) and their wild-type cytoplasmic tails (SEQ ID NO: 3 and 4 respectively) are not “RSV-F proteins of the present disclosure”, as referred to herein. A further independent aspect of the present disclosure is an RSV-F protein encoded by a nucleic acid of the present disclosure. A further independent aspect of the present disclosure provides a multimer comprising protomers, wherein at least one protomer is an RSV-F protein of the present disclosure. Preferably, the multimer Docket No.: 70280WO01 is a trimer of RSV-F proteins of the present disclosure. Preferably, the trimer is a homotrimer (that is, comprising three RSV-F proteins of the present disclosure comprising or consisting of the same primary amino acid sequence). As used herein, an RSV-F protein having a “cytoplasmic tail” / “CT” refers to the presence of residues (e.g.5 residues) that are C-terminal to the residue which aligns with position 549 of SEQ ID NO: 1 or 2 (Y in SEQ ID NO: 1 and SEQ ID NO: 2), when the F1 and transmembrane domains of the RSV-F protein is aligned with positions 137-549 of SEQ ID NO: 1 or 2. Accordingly, the cytoplasmic tail is positioned C-terminal to the transmembrane domain. Preferably, an RSV-F protein having a “cytoplasmic tail” / “CT” refers to the presence of residues (e.g. 5 residues) that are C-terminal to position 549 of the RSV-F protein. For example, the RSV-F construct referred to as ΔCT25 used in the examples (see e.g. Table 2) does not comprise any residues C-terminal to the Y at position 549, and hence does not comprise a cytoplasmic tail. Reference to e.g. deletion of 2-20 residues (and the like) from the CT refers to deletion of at least 2, and no more than 20, residues from the CT (relative to SEQ ID NO: 3 or 4), at any positions. Reference to e.g. deletion of 2-20 residues (and the like) from the C-terminal end of the CT (relative to SEQ ID NO: 3 or 4) refers to deletion of at least the two, and no more than the 20, most C-terminal residues from the CT. That is, at least the deletion of C-terminal residues SN or SK relative to SEQ ID NO: 3 or 4 respectively, and at most the deletion of C-terminal residues TPVTLSKDQLSGINNIAFSN (SEQ ID NO: 142) or TPVTLSKDQLSGINNIAFSK (SEQ ID NO: 143) relative to SEQ ID NO: 3 or 4 respectively. RSV-F proteins of the present disclosure and the mutations which they comprise (relative to a wild- type RSV-F protein), are “engineered”, in the sense that such mutations have been deliberately selected and introduced into the proteins, at least in part in order to enhance expression from nucleic acids. RSV-F proteins of the present disclosure may also be considered “recombinant” (“engineered” and “recombinant” may be used interchangeably in this context). SEQ ID NO: 1 is an RSV-F sequence from a strain of human RSV of the A2 subtype that contains two mutations (K66E and Q101P) relative to GenBank Accession number KT992094 (said mutations resulting from in vitro passaging, see [12]). SEQ ID NO: 2 is the RSV-F sequence from B subtype strain 18537 (Uniprot ID: P13843). SEQ ID NO:1, SEQ ID NO: 2, and any wild-type RSV-F sequence (e.g. RSV-F proteins of other A or B subtype strains) are referred to herein as “wild-type”. Either of SEQ ID NO: 3 and 4 may also be referred to as a “wild type cytoplasmic tail”. RSV-F proteins of the present disclosure may comprise mutations relative to SEQ ID NO: 1 or 2 found in RSV-F proteins from further strains and subtypes, both naturally-occurring and engineered (e.g. RSV-F proteins of further A subtype strains, or further B subtype strains). Hence, RSV-F proteins of the present disclosure may be of the RSV-A or the RSV- B subtype. RSV-F proteins of the present disclosure may also have a specific degree of sequence identity to SEQ ID NO: 1 or 2, e.g. as detailed in the embodiments below. Docket No.: 70280WO01 “Mutation” is used generally herein to encompasses substitution, insertion and deletion of residues. Reference to a sequence / region of an RSV-F protein of the present disclosure “corresponding to positions x-y of SEQ ID NO: z” encompasses sequences / regions which align with positions x-y of SEQ ID NO: z (which, for the avoidance of doubt, includes positions x and y). Alignments may be performed visually, or by any well-known algorithm; e.g. using an NCBI BLAST algorithm, e.g. “blastp”, e.g. on default settings (available at https://blast.ncbi.nlm.nih.gov/Blast.cgi?PAGE=Proteins), or e.g. using the “Clustal Omega” algorithm (see, e.g. [13]), e.g. on default settings; with the Clustal Omega algorithm being preferred. Corresponding residue positions (e.g. position 549 of SEQ ID NO: 1, and so forth) are easily identifiable to the skilled person, and can be identified by aligning the amino acid sequences using any well-known method (visual or algorithm, e.g. as detailed above). Where there is no explicit reference to a reference sequence (e.g. SEQ ID NO: 1 or 2) when residue numbers are provided, standard residue numbering of RSV-F is to be used for the RSV-F protein in question (and such numbering will generally correspond with that of SEQ ID NO 1 or 2). RSV-F proteins of the present disclosure are preferably antigens (or, phrased differently, are antigenic). As such, RSV-F proteins of the present disclosure preferably elicit an immune response when administered to a subject (e.g. via expression from nucleic acids), namely against RSV. The immune response may comprise an antibody response (usually including IgG) and/or a cell-mediated immune response, in particular an antibody response. The immune response will typically recognise the three- dimensional structure of a wild-type pre-fusion RSV-F, in particular one or more epitopes present on the (solvent-exposed) surface of the protein when in the pre-fusion conformation. RSV-F proteins of the present disclosure may also be considered antigens (or, phrased differently, are antigenic) given their ability to be bound by antibodies AM14, D25 and motavizumab; in particular AM14 which recognises trimeric, pre-fusion RSV-F (heavy and light chain sequences of antibodies given below). Generally, RSV-F proteins of the present disclosure may be considered as stabilised in the pre-fusion conformation, following expression from nucleic acids. The pre-fusion conformation of RSV-F proteins of the present disclosure may be confirmed via binding of pre-fusion RSV-F-specific monoclonal antibodies (“pre-fusion mAbs”). For example, RSV-F proteins of the present disclosure may be specifically bound by a pre-fusion mAb comprising a light chain and a heavy chain (LC and HC) selected from the group consisting of: SEQ ID NO: 5 and 6 respectively, and SEQ ID NO: 7 and 8 respectively. The foregoing are the LC and HC sequences of prefusion mAbs AM14 and D25 (see, e.g. [14, 15]), with AM14 being preferred for confirming pre-fusion conformation. Preferably, specific mutations relative to a wild-type RSV-F sequence are present in RSV-F proteins of the present disclosure (e.g. in the ectodomain), which promote and/or stabilise the pre-fusion conformation, following expression from nucleic acids. Such mutations are in addition to those made to the CT. RSV-F proteins of the present disclosure comprise an ectodomain (or at least a portion thereof), and Docket No.: 70280WO01 preferably comprise mutations in the ectodomain according to any of preferred classes (1)-(4) as detailed below, in addition to those made to the CT. In some embodiments, RSV-F proteins of the present disclosure comprise an ectodomain (or at least a portion thereof), and comprise mutations in the ectodomain according to any of preferred classes (1)-(3) as detailed below, in addition to those made to the CT. The ectodomain of SEQ ID NO: 1 and 2 is positions 26-109 and 137-523 (positions 1-25 and 110-136 being removed in the mature protein via signal sequence cleavage and furin processing). An ectodomain of an RSV-F protein of the present disclosure may be positions 26-109 and 137-523 of said RSV-F protein, e.g. with residues numbered according to SEQ ID NO: 1 or 2. Deletions in the cytoplasmic tail In one independent aspect, RSV-F proteins of the present disclosure comprise a cytoplasmic tail; wherein, relative to cytoplasmic tail according to SEQ ID NO: 3 or 4, 2-20 residues are deleted from the cytoplasmic tail of the RSV-F protein (preferably from the C-terminal end thereof). In some embodiments, 3-20 residues are deleted (preferably from said C-terminal end). In some embodiments, at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 or at least 19 residues are deleted (preferably from said C-terminal end). In some embodiments, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 residues are deleted (preferably from said C-terminal end). In some embodiments, 2-5, 3-5, 6-20, 7-20, 8-20, 9-20, 10-20, 11-20, 12-20, 13-20, 14-20, or 15-20 residues are deleted (preferably from said C-terminal end). In preferred embodiments, 2-5, such as 2-4, 2-3 or 3-4, and preferably 3, residues are deleted from the C-terminal end of the CT of the RSV-F protein (relative to a wild-type cytoplasmic tail according to SEQ ID NO: 3 or 4). As demonstrated in e.g. Example 2 (see Figure 2), deletion of the 3 C-terminal residues (“ΔCT3”) enhanced cell-surface trimeric, pre-fusion RSV-F expression from nucleic acids (as measured by AM14 antibody binding) over a period of 96 hours post-transfection, relative to expression of the parental molecule with either an intact or a fully deleted CT. This enhanced expression phenotype was observed for all four RSV-F constructs tested (F318, F319, F(i) and F(ii)). See also e.g. Example 5 (Figure 5A), which uses the “ΔCT5” construct. In a preferred embodiment, the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-31 of SEQ ID NO: 69, or (ii) an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% identical to said positions and optionally the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). In another embodiment, the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-29 of SEQ ID NO: 70, or (ii) an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% identical to said positions and optionally the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii) Docket No.: 70280WO01 In preferred embodiments, 6-13, such as 7-13, 8-12, 9-11, 9-10 or 10-11, and preferably 10, residues are deleted from the C-terminal end of the CT of the RSV-F protein (relative to a wild-type cytoplasmic tail according SEQ ID NO: 3 or 4). As demonstrated in e.g. Example 5 (see Figure 5), deletion of the 10 C-terminal residues (“ΔCT10”) enhanced cell-surface trimeric, pre-fusion RSV-F expression from nucleic acids (as measured by AM14 antibody binding) over a period of 47 hours post-transfection, relative to expression of the parental molecule with either an intact or a fully deleted CT. In a preferred embodiment, the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-24 of SEQ ID NO: 71, or (ii) an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% identical to said positions and optionally the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). In preferred embodiments, 14-16, such as 14-15 or 15-16, and preferably 15, residues are deleted from the C-terminal end of the CT of the RSV-F protein (relative to a wild-type cytoplasmic tail according SEQ ID NO: 3 or 4). As demonstrated in e.g. Example 5 (see Figure 5), deletion of the 15 C-terminal residues (“ΔCT15”) enhanced cell-surface trimeric, pre-fusion RSV-F expression from nucleic acids (as measured by AM14 antibody binding) over a period of 47 hours post-transfection, relative to expression of the parental molecule with either an intact or a fully deleted CT. In a preferred embodiment, the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-19 of SEQ ID NO: 72, or (ii) an amino acid sequence at least 60%, 70%, 80% or 90% identical to said positions and optionally the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). In more preferred embodiments, 16-20, such as 17-20, 18-20 or 19-20, and preferably 20, residues are deleted from the C-terminal end of the CT of the RSV-F protein (relative to a wild-type cytoplasmic tail according SEQ ID NO: 3 or 4). As demonstrated in e.g. Example 2 (see Figure 2), deletion of the 20 C-terminal residues (“ΔCT20”) enhanced cell-surface trimeric, pre-fusion RSV-F expression from nucleic acids (as measured by AM14 antibody binding) over a period of 96 hours post-transfection, relative to expression of the parental molecule with either an intact or a fully deleted CT. Such expression was also enhanced compared to “ΔCT3” construct, and this phenotype was observed for all four RSV-F constructs tested (F318, F319, F(i) and F(ii)). See also e.g. Example 5 (Figure 5A), where maximal trimeric, prefusion expression was observed with the ΔCT20 construct. See also e.g. Example 6, where at low doses of RNA (0.2 μg), constructs with a ΔCT20 tended to elicit a more potent neutralising antibody response in vivo compared to their parental molecules with a fully intact CT (see e.g. Figure 7B). Hence, deletion of 17-20, such as 18-20 or 19-20 C-terminal residues, and especially deletion of the 20 C-terminal residues, is more preferred than deletion of other numbers of residues from the C-terminus. In another more preferred embodiment, the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-14 of SEQ ID NO: 73, or (ii) an amino acid sequence at least 60% or 80% identical to said positions and optionally the same length as Docket No.: 70280WO01 said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). Generally, the deletions outlined above increase the cell-surface expression of RSV-F protein from RNA, relative to an RSV-F protein having the same amino acid sequence absent deletions, e.g. comprising a wild-type cytoplasmic tail, e.g. according to SEQ ID NO: 3 or 4 (e.g. over at least 24, 48, 72 or 96 hours; or e.g. over 24, 48, 72 or 96 hours). Generally, the deletions outlined above increase the cell-surface expression of RSV-F protein in trimeric, pre-fusion form from RNA, relative to expression in such form of an RSV-F protein having the same amino acid sequence absent such deletions, e.g. comprising a wild-type cytoplasmic tail, e.g. according to SEQ ID NO: 3 or 4 (e.g. over at least 24, 48, 72 or 96 hours; or e.g. over 24, 48, 72 or 96 hours). In a further independent aspect, RSV-F proteins of the present disclosure comprise a cytoplasmic tail; wherein the cytoplasmic tail is 5-23 residues in length. In a preferred embodiment of said further independent aspect, the cytoplasmic tail is 8-12, such as 9- 12, 10-12, 9-11, 9-10, 10-11, or preferably 10 residues in length. Preferably, the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-19 of SEQ ID NO: 72, or (ii) an amino acid sequence at least 60%, 70%, 80% or 90% identical to said positions and the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). See discussion of ΔCT15 in the preceding paragraphs. In a preferred embodiment of said further independent aspect, the cytoplasmic tail is 10-18, such as 11-17, 12-16, 13-16, 14-15, or preferably 15 residues in length. Preferably, the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-24 of SEQ ID NO: 71, or (ii) an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% identical to said positions and the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). See discussion of ΔCT10 in the preceding paragraphs. In a preferred embodiment of said further independent aspect, the cytoplasmic tail is 18-23, 19-23, 20- 23, 21-23, 21-22, 22-23 or preferably 22 residues in length. Preferably, the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-31 of SEQ ID NO: 69, or (ii) an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% identical to said positions and the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). See discussion of ΔCT3 in the preceding paragraphs Alternatively, the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-29 of SEQ ID NO: 70, or (ii) an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% identical to said positions and the same length as said positions; and wherein Docket No.: 70280WO01 the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). See discussion of ΔCT5 in the preceding paragraphs. In a more preferred embodiment of said further independent aspect, the cytoplasmic tail 5-7, 5-6, 4-5, or more preferably 5 residues in length. Preferably, the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-14 of SEQ ID NO: 73, or (ii) an amino acid sequence at least 60% or 80% identical to said positions and the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). See discussion of ΔCT20 in the preceding paragraphs. Generally, the cytoplasmic tail lengths outlined above increase the cell-surface expression of RSV-F protein from RNA, relative to an RSV-F protein having the same amino acid sequence but comprising a wild-type cytoplasmic tail, e.g. according to SEQ ID NO: 3 or 4 (e.g. over at least 24, 48, 72 or 96 hours; or e.g. over 24, 48, 72 or 96 hours). Generally, the cytoplasmic tail lengths outlined above increase the cell-surface expression of RSV-F protein in trimeric, pre-fusion form from RNA, relative to expression in such form of an RSV-F protein having the same amino acid sequence but comprising a wild-type cytoplasmic tail, e.g. according to SEQ ID NO: 3 or 4 (e.g. over at least 24, 48, 72 or 96 hours; or e.g. over 24, 48, 72 or 96 hours). When determining the effect of deletions and/or length of cytoplasmic tail (e.g. according to either independent aspect of the present disclosure as outlined above), trimeric, pre-fusion RSV-F expression is typically assessed using AM14 antibody binding (or defined differently, using binding of an antibody comprising a light chain (LC) according to SEQ ID NO: 5 and a heavy chain (HC) according SEQ ID NO: 6). AM14 antibody binding may be assayed using indirect immunofluorescent labelling, e.g. using the protocol in the examples (see subsection “Indirect immunofluorescent labelling and detection of surface-expressed RSV F”). Cell-surface expression may be assessed in fibroblasts, preferably human fibroblasts, preferably human foreskin fibroblasts, preferably human primary BJ cells, preferably the CRL-2522 cell line (deposited at American Type Culture Collection (ATCC) under said accession number and publicly available). Mutations to the ectodomain (1) In embodiments disclosed herein as preferred class (1), or simply “(1)”, RSV-F proteins of the present disclosure may comprise an ectodomain comprising an F2 and an F1 domain, and the substitution relative to a wild-type RSV-F ectodomain (e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2) of a residue for a C residue in both of the F2 and F1 domains. When expressed, the C residues form a disulphide bond connecting the F2 and F1 domains. Said disulphide bond is not present in wild-type RSV-F, and so may be considered “artificial” or “engineered”. Said C residues, and the disulphide bond formed thereby, generally promote and/or stabilise the pre-fusion conformation of RSV-F. Docket No.: 70280WO01 For example, in embodiments of (1), RSV-F proteins of the present disclosure may comprise a C residue at both of positions 55 and 188 (not present in wild-type). Alternatively, the C residue in the F1 domain may be within the fusion peptide of the RSV-F protein; optionally wherein the fusion peptide is the region corresponding to positions 137-157 of SEQ ID NO: 1 or 2. For example, the C residue may be within the region of the RSV-F protein corresponding to positions 143-153, 146-150 or 147-149 of SEQ ID NO: 1 or 2; and preferably at position 148 of the RSV-F protein. The C residue in the F2 domain may be within the region of the RSV-F protein corresponding to positions 99-105, 100-104 or 102-104 of SEQ ID NO: 1 or 2; and preferably at position 103 of the RSV-F protein. In addition, in further embodiments of (1), RSV-F proteins of the present disclosure may comprise the substitution (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2) of one or more small aliphatic or small polar residues that are buried in the pre-fusion conformation (in wild-type), for larger aliphatic or larger aromatic residues. Said small aliphatic or small polar residues may be, for example, a S, T, G, A, V, or R residue. Said larger aliphatic or larger aromatic residues may be, for example, a I, Y, L, H, M or W residue. Such substitutions generally further promote and/or stabilise the pre-fusion conformation. In such further embodiments of (1), RSV-F proteins of the present disclosure may, for example, comprise: (i) substitution at position 190, 55, 62, 155, or 290 for I, Y, L, H, or M; (ii) substitution at position 54, 58, 189, 219, or 397 for I, Y, L, H, or M; (iii) substitution at position 151 for A or H; (iv) substitution at position 147 or 298 for I, L, H, or M; (v) substitution at position 164, 187, 192, 207, 220, 296, 300, or 495 for I, Y, H; or (vi) substitution at position 106 for W; wherein substitutions at position 190 according to (i) are preferred; wherein substitution at position 190 for I is a preferred substitution at said position. In addition to, or instead of, one or more substitutions of buried residues as defined above, in further embodiments of (1), RSV-F proteins of the present disclosure may comprise substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2) which reduce inter-protomer repulsive ionic interactions or increase inter-protomer attractive ionic interactions with E487 and D489 on an adjacent RSV-F protomer (when the RSV-F protein is in trimeric form). Such substitutions generally further promote and/or stabilise the pre-fusion conformation. In such further embodiments of (1), RSV-F proteins of the present disclosure may comprise the substitution of a D or E residue for S, T, N, H, P, F, L or Q within the region of the RSV- F protein corresponding to positions 474-523 of SEQ ID NO: 1 or 2 (a.k.a. the heptad repeat B Docket No.: 70280WO01 (“HRB”) domain), such as D486S/H/N/T/P or E487Q/T/S/L/H. In such further embodiments of (1), RSV-F proteins of the present disclosure may, for example, comprise: (vii) substitution at position 82, 92, or 487 for D, F, Q, T, S, L, or H; (viii) substitution at position 315, 394, or 399 for F, M, R, S, L, I, Q, or T; (ix) substitution at position 392, 486, or 489 for H, S, N, T, or P; and/or (x) substitution at position 106 or 339 for F, Q, N, or W; wherein substitutions at position 486 according to (ix) are preferred; wherein substitution at position 486 for S is a preferred substitution at said position. In preferred embodiments of (1), RSV-F proteins of the present disclosure comprise the substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2) 103C, 148C, 190I and 486S. Such RSV-F proteins may be of the RSV-A or B subtype. See, e.g. construct F(i) as tested in the examples (in particular, Example 2; Figure 2 D). In such preferred embodiments of (1), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 26-109 and 137-523 of SEQ ID NO: 17; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto and comprising the 103C, 148C, 190I, and 486S substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). In other embodiments of (1), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) a portion of positions 26-109 and 137-523 of SEQ ID NO: 17, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof and comprising the 103C, 148C, 190I, and 486S substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2); or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical to such a portion which comprises the 103C, 148C, 190I, and 486S substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). In a mature RSV-F protein / ectodomain, the region corresponding to positions 110- 136 of SEQ ID NO 1 or 2 (which may be positions 110-136 of the RSV-F protein) may be absent due to furin processing. Hence, reference to “an amino acid sequence” (as used here, or in further subsections detailed below) may refer to two non-contiguous amino acid chains. However, nucleic acids of the present disclosure will typically encode an RSV-F protein of the present disclosure comprising the region corresponding to positions 110-136 of SEQ ID NO 1 or 2 (which may be positions 110-136 of the RSV-F protein). All of the above mutations in the subsection preferably promote and/or stabilise the pre-fusion conformation of RSV-F. Docket No.: 70280WO01 Mutations to the ectodomain (2) In embodiments disclosed herein as preferred class (2), or simply “(2)”, RSV-F proteins of the present disclosure may comprise the substitution of at least one residue in the ectodomain relative to a wild- type RSV-F ectodomain (e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2), at position 67 and/or 215 (typically both). Examples of such substitutions include: (i) substitution at position 67 for I; and/or (ii) substitution at position 215 for P; wherein a combination of substitutions according (i) and (ii) is a preferred set of substitutions. In further embodiments of (2), RSV-F proteins of the present disclosure may comprise, in addition to the above substitutions(s), a substitution at position 486 or 487 for a residue without a negatively charged side chain. Examples of such substitutions include: (iii) substitution at position 486 for N; or (iv) substitution at position 487 for Q, N or I; wherein substitution at position 486 for N is a preferred substitution. In further embodiments of (2), RSV-F proteins of the present disclosure may comprise, in addition to the above substitution(s), a linker sequence joining the F2 and F1 domains, e.g. wherein the linker sequence is from 1-10 amino acids (e.g. according to SEQ ID NO: 11, 12, 13 or 14, in particular according to SEQ ID NO: 14). In other embodiments of (2), the linker sequence is absent. In further embodiments of (2), RSV-F proteins of the present disclosure preferably comprise combinations of the above substitutions, potentially in addition to further substitutions and/or use of a linker, such as: (v) 67I and 215P, optionally with a linker sequence joining the F2 and F1 domains (e.g. according to SEQ ID NO: 14); (vi) 67I, 215P and 487Q, optionally with a linker sequence joining the F2 and F1 domains (e.g. according to SEQ ID NO: 14) (vii) 66E, 67I, 76V, 215P and 486N (viii) 66E, 67I, 76V, 215P and 486G; or (ix) 101Q, 152M, 215P and 486N (e.g.152M, 226M, 486N, 215P, 2031 and 101Q), optionally wherein the RSV-F protein is of the B subtype; wherein substitutions according to (v) without a linker sequence joining the F2 and F1 domains, and substitutions according to (vii), are preferred. Docket No.: 70280WO01 See, e.g. construct F(ii) as tested in the examples (in particular, Example 2 / Figure 2A; Example 5 / Figure 5A). In preferred embodiments of (2), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 26-109 and 137-523 of SEQ ID NO: 16; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto and comprising the N67I and S215P substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). In other embodiments of (2), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) a portion of positions 26-109 and 137-523 of SEQ ID NO: 16, such a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof and comprising the N67I and S215P substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2); or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical to such a portion which comprises the N67I and S215P substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). A further independent aspect of the present disclosure is a recombinant RNA encoding an RSV-F protein comprising an ectodomain according to preferred class (2). In some embodiments, the RSV-F protein (encoded by said RNA) does not comprise a cytoplasmic tail. A further independent aspect of the present disclosure is an RSV-F protein encoded by said RNA. As demonstrated in e.g. Example 3 (see Figure 2), deletion of the entire CT from construct F(ii) enhanced cell-surface trimeric, pre-fusion expression from nucleic acids (as measured by AM14 antibody binding) over a period of 96 hours post-transfection, relative to expression of the parental F(ii) construct with an intact CT. Such nucleic acids and proteins are also referred to herein as nucleic acids and proteins “of the present disclosure”.All of the above mutations in the subsection preferably promote and/or stabilise the pre- fusion conformation of RSV-F. Mutations to the ectodomain (3) In embodiments disclosed herein as preferred class (3), or simply “(3)”, RSV-F proteins of the present disclosure may comprise the substitution of at least two residues in the ectodomain relative to a wild- type RSV-F ectodomain (e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2) for C residues, introducing a disulphide bond. Said disulphide bond preferably promotes and/or stabilises the pre- fusion conformation. Said disulphide bond is preferably an intra-protomer disulphide bond. Examples of positions which may be substituted for C residues to introduce said disulphide bond include 155C+290C (e.g. S155C + S290C). In addition to, or instead of, a disulphide bond as defined above (in particular joining the specified positions), in further embodiments of (3), RSV-F proteins of the present disclosure may comprise the substitution of at least two further residues in the ectodomain relative to a wild-type RSV-F ectodomain (e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2) for C residues, introducing a further Docket No.: 70280WO01 disulphide bond Said disulphide bond preferably promotes and/or stabilises the pre-fusion conformation. Said disulphide bond is preferably an inter-protomer disulphide bond. Examples of positions which may be substituted for C residues to introduce said disulphide bond include 149C+458C (e.g. A149C+Y458C). In addition to either, or both, disulphide bonds as defined above (in particular joining the specified positions), in further embodiments of (3), RSV-F proteins of the present disclosure may comprise the substitution of one or more residues in the ectodomain relative to a wild-type RSV-F ectodomain (e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2), wherein the residues have a side chain that is buried in a hydrophobic cavity in the pre-fusion conformation (in wild-type). Such substitutions may introduce residues with hydrophobic side chains (e.g. F, L, A, V, I, M, Y or W) so as to fill such a hydrophobic cavity. Examples of positions which may be substituted for C residues to introduce said disulphide bond include 190F+207L (e.g. S190F + V207L). In further embodiments of (3), RSV-F proteins of the present disclosure may comprise, in addition to the above substitution(s) / disulphide bonds, a linker sequence joining the F2 and F1 domains, e.g. wherein the linker sequence is from 1-10 amino acids (e.g. according to SEQ ID NO: 11, 12, 13 or 14, in particular according to SEQ ID NO: 13). In other embodiments of (3), the linker sequence is absent. In further embodiments of (3), RSV-F proteins of the present disclosure preferably comprise combinations of the above substitutions, optionally in addition to the use of a linker, such as: (i) 149C, 155C, 190F, 207L, 290C and 458C, preferably with a linker sequence joining the F2 and F1 domains (e.g. according to SEQ ID NO: 13); (ii) 102A, 149C, 155C, 190F, 207L, 290C, 373R, 379V, 447V and 458C, preferably with a linker sequence joining the F2 and F1 domains (e.g. according to SEQ ID NO: 13); or (iii) 155C, 190F, 207L and 290C; wherein substitutions and linkers according to (i) or (ii) are preferred. In (i) and (ii), the linker may replace wild-type residues 104-144 (i.e. there is ^104-144 deletion, which said positions being replaced by the linker, e.g. according to SEQ ID NO: 13). In preferred embodiments of (3), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 26-109 and 137-523 of SEQ ID NO: 15; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto and comprising the 155C, 190F, 207L and 290C substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). In other embodiments of (2), RSV-F proteins of the present disclosure may comprise an ectodomain comprising Docket No.: 70280WO01 or consisting of: (i) a portion of positions 26-109 and 137-523 of SEQ ID NO: 15, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof and comprising the S155C, S190F, V207L and S290C substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2); or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical to such a portion which comprises the S155C, S190F, V207L and S290C substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). In other preferred embodiments of (3), RSV-F proteins of the present may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 26-103 and 106-485 of SEQ ID NO: 18; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto and comprising the 149C, 155C, 190F, 207L, 290C and 458C substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). In other embodiments of (3), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) a portion of positions 26-103 and 106-485 of SEQ ID NO: 18, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof and comprising the 149C, 155C, 190F, 207L, 290C and 458C substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2); or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical to such a portion which comprises the 149C, 155C, 190F, 207L, 290C and 458C substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). In other preferred embodiments of (3), RSV-F proteins of the present may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 26-103 and 106-485 of SEQ ID NO: 18; (ii) or an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto and comprising the 102A, 149C, 155C, 190F, 207L, 290C, 373R, 379V, 447V and 458C substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). In other embodiments of (3), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) a portion of positions 26-103 and 106-485 of SEQ ID NO: 18, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof and comprising the 102A, 149C, 155C, 190F, 207L, 290C, 373R, 379V, 447V and 458C substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2); or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical to such a portion which comprises the 102A, 149C, 155C, 190F, 207L, 290C, 373R, 379V, 447V and 458C substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). All of the above mutations in the subsection preferably promote and/or stabilise the pre-fusion conformation of RSV-F. Docket No.: 70280WO01 A further independent aspect of the present disclosure is a recombinant RNA encoding an RSV-F protein comprising an ectodomain according to preferred class (3). In some embodiments, the RSV-F protein (encoded by said RNA) does not comprise a cytoplasmic tail. A further independent aspect of the present disclosure is an RSV-F protein encoded by said RNA. Such nucleic acids and proteins are also referred to herein as nucleic acids and proteins “of the present disclosure”. Mutations to the ectodomain (4) In embodiments disclosed herein as preferred class (4), or simply “(4)”, RSV-F proteins of the present disclosure may comprise the substitution of residues in the ectodomain relative to a wild-type ectodomain (e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2), according to any of (a), (b) and (c) defined below: (a): substitution at position 55 for T, C, V, I; preferably T, C or V; preferably T or V; preferably T; (b): substitution at position 215 for A, P, V, I, or F; preferably A, V, I, or F; preferably A or P; preferably A; (c): substitution at position 228 for K, R, N, W, D, E, Q, H, S, T or Y; preferably K, R, W, N, Q, H, S, T or Y; preferably K, R, Q and N; preferably K, R or Q; preferably K or R, preferably K; Combinations of substitutions according to of (a), (b) or (c) will typically be present, such as: (a) and (b), (a) and (c), (b) and (c), or preferably (a), (b) and (c). As detailed in Example 9, a minimal substitution screen revealed the 55T substitution to be a likely driver of the pre-fusion conformation (see Figure 15; design F308 – recombinant protein tested). Without wishing to be bound by this theory, T in place of S (wild-type) at position 55 provides a slightly larger residue which (from in silico three-dimensional structural analysis, see Figure 12) appears to be accommodated well in the hydrophobic pocket discussed above, without generating significant steric clashes. Moreover, the addition of the CH3 group of T appears to provide new, energetically favourable VDW contacts of the type discussed above. Furthermore, alternative substitutions provided for position 55 by ROSETTA software include C and V (based on all amino acids being allowed (no evolutionary constraints) with energy thresholds of 0.0, -0.1 or -0.5 being used). Docket No.: 70280WO01 Furthermore, as detailed in Example 9, a minimal substitution screen revealed the 215A substitution to be a likely driver of the pre-fusion conformation (see Figure 15; design F309 – recombinant protein tested). Without wishing to be bound by this theory, removal of the hydrophilic OH group, as S (wild- type) is substituted for A, is likely favourable to the packing and rigidity of the loop (see Figure 13). Furthermore, the A residue at position 215 may provide energetically-favourable VDW contacts with positions 79, 206, 203, and/or T219. Such packing, rigidification and/or VDW contacts may inhibit, at least partly inhibit, or completely inhibit the transition from pre-fusion to post-fusion conformation of RSV-F (in particular, inhibition of the relative motion of the two α helices adjacent to the loop(generally the α4 and α5 helices of RSV-F), or, defined differently, inhibition of refolding of the HRC and HRA domains). Furthermore, the side chains of P, V, I or F may also reduce conformational freedom of the loop, thus also being favourable to the packing and rigidification of the loop. Furthermore, as detailed in Example 9, a minimal substitution screen revealed the 228K substitution alone to be able to achieve pre-fusion RSV-F (see Figure 15; design F310 – recombinant protein tested). Without wishing to be bound by this theory, K at position 228 appears to result in an H bond with Y250 on the same protomer (see Figure 11, dashed line indicating hydrogen bond). Said H bonding may stabilise Y250 to form a tertiary cation-pi-anion interaction between E232, Y250 and R235 (E232 and Y250 being on one protomer, with R235 being on an adjacent protomer). E, Y and R are one of the dominant triads for such a tertiary cation-pi-anion interaction (see, e.g. [16]). Furthermore, residues with other H bond donors in their side chains (such as R or Q, in particular R) at position 228 may also provide this stabilising H bond with Y250. In addition, based on the proximity and orientation of the E232 side chain (see Figure 11), substitution for N may also provide a stabilising hydrogen bond with Y250. In all foregoing embodiments in this subsection, optionally RSV-F proteins of the present disclosure may comprise a substitution at position 250 for D. A 250D substitution may strengthen a cross- protomer interaction with R235 (wild-type residue) by forming a salt bridge between the two residues. For an example of an engineered cross-protomer salt bridge between D and R residues to stabilise a multimeric protein in a pre-fusion conformation, see [17] (Figure 1; D961–R765 salt bridge). Furthermore, D comprises an H bond acceptor moiety and so the Y250D substitution would maintain the preferred hydrogen bond between positions 250 and 228. In embodiments of (4), in addition to (a), (b) and/or (c), RSV-F proteins of the present disclosure may comprise further substitutions, such as: a substitution at position 152 for R, L or W (optionally R or W; wherein substitution for R is preferred); a substitution at position 315 for I or V (wherein substitution for I is preferred); Docket No.: 70280WO01 a substitution at position 346 for Q, D, H, K, N, R, S or W (optionally Q, D, H, K, N, R or S; wherein substitution for Q is preferred); a substitution at position 445 for D; a substitution at position 455 for V or I (wherein substitution for V is preferred); and/or a substitution at position 459 for M; in particular: a substitution at position 152 for R, L or W (optionally R or W; wherein substitution for R is preferred); a substitution at position 315 for I or V (wherein substitution for I is preferred); a substitution at position 346 for Q, D, H, K, N, R, S or W (optionally Q, D, H, K, N, R or S; wherein substitution for Q is preferred); a substitution at position 445 for D; a substitution at position 455 for V or I (wherein substitution for V is preferred); and a substitution at position 459 for M; in particular: a substitution at position 152 for R; a substitution at position 315 for I; a substitution at position 346 for Q; a substitution at position 445 for D; a substitution at position 455 for V; and a substitution at position 459 for M. In preferred embodiments of (4), RSV-F proteins of the present disclosure may comprise: a substitution at position 55 for T; a substitution at position 152 for R; a substitution at position 215 for A; a substitution at position 228 for K; a substitution at position 315 for I; Docket No.: 70280WO01 a substitution at position 346 for Q; a substitution at position 445 for D; a substitution at position 455 for V; and a substitution at position 459 for M; more preferably: a substitution at position 55 for T; a substitution at position 152 for R; a substitution at position 215 for A; a substitution at position 228 for K; a substitution at position 315 for I; a substitution at position 346 for Q; a substitution at position 445 for D; a substitution at position 455 for V; a substitution at position 459 for M; a substitution at position 486 for C; and a substitution at position 490 for C. In some embodiments of (4), RSV-F proteins of the present disclosure further comprise a substitution at position 211 for N and/or (optionally and) a substitution at position 348 for N. In some embodiments of (4), relative to a wild-type ectodomain (e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2), a pair of C residues is introduced into the region of the RSV-F protein corresponding to positions 474-523 of SEQ ID NO: 1 or 2 (a.k.a. the HRB domain) which form a disulphide bond. In particular, the pair of C residues may be within the region corresponding to positions 474-513 of SEQ ID NO: 1 or 2. Preferably, this is an intra-protomer disulphide bond (i.e. linking two C residues within the same protomer). In some embodiments of (4), a first C residue of said pair may be within a region of the RSV-F protein corresponding to positions 478-501 of SEQ ID NO: 1 or 2, and/or (optionally and) a second C residue of said pair may be within a region corresponding to positions 482-504 of SEQ ID NO: 1 or 2. Examples of such C residue pairs include those at positions: 486 and 490, 485 and 494, 480 and 497, 490 and 494, 479 and 482, 484 and 498, 487 and 490, 491 and 494, 482 and 502, 478 and 483, 481 and 501, 482 and 499, 486 and 489, 486 and 488, 485 and 494, 480 and 487, or 501 and 504 of SEQ ID NO: 1 or 2. C residues in these positions Docket No.: 70280WO01 were computationally predicted to form intra-protomer disulphide bonds, based on a distance criterion of 5Å between Cβ atoms in the RSV-F pre-fusion conformation (see e.g. Example 14); and/or are present in designs F528, F647, F651 and 2C (see e.g. Examples 8, 11 and 13) . In some embodiments of (4), a first C residue of said pair may be within a region of the RSV-F protein corresponding to positions 478-491 of SEQ ID NO: 1 or 2, and/or (optionally and) a second C residue of said pair may be within a region corresponding to positions 482-502 of SEQ ID NO: 1 or 2. Examples of such C residue pairs include those at positions: 486 and 490, 485 and 494, 480 and 497, 490 and 494, 479 and 482, 484 and 498, 487 and 490, 491 and 494, 482 and 502, or 478 and 483 of SEQ ID NO: 1 or 2. In particular embodiments of (4), a first C residue of said pair is within a region of the RSV-F protein corresponding to positions 480-486 of SEQ ID NO: 1 or 2, and/or (optionally and) a second C residue of said pair is within a region corresponding to positions 490-497 of SEQ ID NO: 1 or 2. Examples of such C residue pairs include those at positions: 486 and 490, 485 and 494, or 480 and 497 of SEQ ID NO: 1 or 2. Preferably, the pair of C residues is at positions 486 and 490 of SEQ ID NO: 1 or 2 (see inter alia, designs F528, F647, F651 and 2C in e.g. Examples 8, 11 and 13). According to preferred embodiments of (4), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 25-109 and 137-523 of SEQ ID NO: 21; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto, preferably comprising the substitutions 55T, 152R, 210H, 211N, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 445D, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to (4), RSV-F proteins of the present disclosure may alternatively comprise an ectodomain comprising or consisting of a portion of positions 25-109 and 137-523 of SEQ ID NO: 21, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof. Said portion preferably includes the substitutions 55T, 152R, 210H, 211N, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 445D, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to preferred embodiments of (4), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 25-109 and 137-523 of SEQ ID NO: 22; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto, preferably comprising the substitutions 55T, 152R, S211N, 215A, 228K, 315I, 346Q, 348N, 445D, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to (4), RSV-F proteins of the present disclosure may alternatively comprise an ectodomain comprising or consisting of a portion of positions 25-109 and 137-523 of SEQ ID NO: 22, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof. Said portion preferably includes the substitutions 55T, 152R, S211N, 215A, 228K, 315I, 346Q, 348N, 445D, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). Docket No.: 70280WO01 According to preferred embodiments of (4), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 25-109 and 137-523 of SEQ ID NO: 23; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto, preferably comprising the substitutions 55T, 215A, 228K, 241N, 315I, 348N, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to (4), RSV-F proteins of the present disclosure may alternatively comprise an ectodomain comprising or consisting of a portion of positions 25-109 and 137-523 of SEQ ID NO: 23, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof. Said portion preferably includes the substitutions 55T, 215A, 228K, 241N, 315I, 348N, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to preferred embodiments of (4), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 25-109 and 137-523 of SEQ ID NO: 24; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto, preferably comprising the substitutions 55T, 215A, 228K, 315I, 348N, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to (4), RSV-F proteins of the present disclosure may alternatively comprise an ectodomain comprising or consisting of a portion of positions 25-109 and 137-523 of SEQ ID NO: 24, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof. Said portion preferably includes the substitutions 55T, 215A, 228K, 315I, 348N, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to preferred embodiments of (4), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 25-109 and 137-523 of SEQ ID NO: 25; (ii) or an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto, preferably comprising the substitutions 55T, 215A, 228K, 315I, 348N, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to (4), RSV-F proteins of the present disclosure may alternatively comprise an ectodomain comprising or consisting of a portion of positions 25-109 and 137-523 of SEQ ID NO: 25, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof. Said portion preferably includes the substitutions 55T, 215A, 228K, 315I, 348N, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to preferred embodiments of (4), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 25-109 and 137-523 of SEQ ID NO: 26; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto, preferably comprising the substitutions 55T, 152R, 210H, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 445D, 455V and 459M (relative to a wild-type RSV-F Docket No.: 70280WO01 ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to (4), RSV-F proteins of the present disclosure may alternatively comprise an ectodomain comprising or consisting of a portion of positions 25-109 and 137-523 of SEQ ID NO: 26, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof. Said portion preferably includes the substitutions 55T, 152R, 210H, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 445D, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to preferred embodiments of (4), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 25-109 and 137-523 of SEQ ID NO: 27; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto, preferably comprising the substitutions 55T, 152R, 210H, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). See e.g. construct F319 as tested in the examples. According to (4), RSV-F proteins of the present disclosure may alternatively comprise an ectodomain comprising or consisting of a portion of positions 25-109 and 137-523 of SEQ ID NO: 27, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof. Said portion preferably includes the substitutions 55T, 152R, 210H, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to preferred embodiments of (4), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 25-109 and 137-523 of SEQ ID NO: 28; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto, preferably comprising the substitutions 55T, 152R, 211N, 215A, 228K, 315I, 346Q, 348N, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to (4), RSV-F proteins of the present disclosure may alternatively comprise an ectodomain comprising or consisting of a portion of positions 25-109 and 137-523 of SEQ ID NO: 28, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof. Said portion preferably includes the substitutions 55T, 152R, 211N, 215A, 228K, 315I, 346Q, 348N, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to preferred embodiments of (4), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 25-109 and 137-523 of SEQ ID NO: 29; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto, preferably comprising the substitutions 55T, 152R, 215A, 228K, 315I, 346Q, 348N, 445D, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). See e.g. construct F318 as tested in the examples. According to (4), RSV-F proteins of the present disclosure may alternatively comprise an ectodomain comprising or Docket No.: 70280WO01 consisting of a portion of positions 25-109 and 137-523 of SEQ ID NO: 29, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof. Said portion preferably includes the substitutions 55T, 152R, 215A, 228K, 315I, 346Q, 348N, 445D, 455V and 459M (relative to a wild- type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to preferred embodiments of (4), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 25-109 and 137-523 of SEQ ID NO: 30; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto, preferably comprising the substitutions 55T, 152R, 215A, 228K, 315I, 346Q, 348N, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to (4), RSV-F proteins of the present disclosure may alternatively comprise an ectodomain comprising or consisting of a portion of positions 25-109 and 137-523 of SEQ ID NO: 30, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof. Said portion preferably includes the substitutions 55T, 152R, 215A, 228K, 315I, 346Q, 348N, 455V and 459M (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to preferred embodiments of (4), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 26-109 and 137-523 of SEQ ID NO: 82; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto, preferably comprising the substitutions 55T, 152R, 211N, 215A, 228K, 315I, 346Q, 348N, 445D, 455V, 459M, 486C and 490C (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to (4), RSV-F proteins of the present disclosure may alternatively comprise an ectodomain comprising or consisting of a portion of positions 26-109 and 137-523 of SEQ ID NO: 82, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof. Said portion preferably includes the substitutions 55T, 152R, 211N, 215A, 228K, 315I, 346Q, 348N, 445D, 455V, 459M, 486C and 490C (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to preferred embodiments of (4), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 26-472 of SEQ ID NO: 108; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto, preferably comprising the substitutions 55T, 152R, 215A, 228K, 315I, 346Q, 445D, 455V, 459M, 486C and 490C (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2) and a GS linker at positions 103 and 104. According to (4), RSV-F proteins of the present disclosure may alternatively comprise an ectodomain comprising or consisting of a portion of positions 26-472 of SEQ ID NO: 108, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof. Said portion preferably includes the substitutions 55T, 152R, 215A, 228K, 315I, 346Q, 445D, 455V, 459M, 486C and 490C (relative to a wild-type RSV-F Docket No.: 70280WO01 ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2) and a GS linker at positions 103 and 104 According to more preferred embodiments of (4), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 26-109 and 137-523 of SEQ ID NO: 104; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto, preferably comprising the substitutions 55T, 152R, 215A, 228K, 315I, 346Q, 445D, 455V, 459M, 486C and 490C (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). According to (4), RSV-F proteins of the present disclosure may alternatively comprise an ectodomain comprising or consisting of a portion of positions 26-109 and 137-523 of SEQ ID NO: 104, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof. Said portion preferably includes the substitutions 55T, 152R, 215A, 228K, 315I, 346Q, 445D, 455V, 459M, 486C and 490C (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2). In further embodiments of (4), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of: (i) an amino acid sequence according to positions 25-109 and 137-523 of any of SEQ ID NO: 31-37; or (ii) an amino acid sequence at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% identical thereto (preferably including all substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2) present in the amino acid sequence according to any of SEQ ID NO: 31-37 where applicable). In further embodiments of (4), RSV-F proteins of the present disclosure may comprise an ectodomain comprising or consisting of a portion of positions 25-109 and 137-523 of SEQ ID NO: 31-37, such as a portion at least 70%, 80%, 85%, 90%, 95%, 99% or 99.5% the length thereof (preferably including all substitutions (relative to a wild-type RSV-F ectodomain, e.g. positions 26-109 and 137-523 of SEQ ID NO: 1 or 2) present in the amino acid sequence according to any of SEQ ID NO: 31-37 where applicable). All of the above mutations in the subsection preferably promote and/or stabilise the pre-fusion conformation of RSV-F. General features of nucleic acids and RSV-F proteins Nucleic acids of the present disclosure may encode an RSV-F protein of the present disclosure, preferably according to (1), (2), (3) or (4), comprising or consisting of an amino acid sequence having at least 70%, 75%, 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, or preferably at least 95%, 96%, 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, or 99.5% sequence identity to positions 1-549 of SEQ ID NO: 1 or 2. In some embodiments, the signal peptide (positions 1-25 of SEQ ID NO: 1 and 2) is not considered in the above sequence identity assessment. Hence, in some embodiments, nucleic acids of the present disclosure encode an RSV-F protein of the present disclosure, preferably according to (1), (2), (3) or Docket No.: 70280WO01 (4), comprising or consisting of an amino acid sequence having at least 70% sequence identity to positions 26-549 SEQ ID NO: 1 or 2, such as at least 75%, 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, or preferably at least 95%, 96%, 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, or 99.5% sequence identity to positions 26-549 SEQ ID NO: 1 or 2. In some embodiments, RSV-F proteins of the present disclosure comprise an E residue at position 66, and a P residue at position 101. In some embodiments, nucleic acids of the present disclosure encode an RSV-F protein of the present disclosure, preferably according to (1), (2), (3) or (4), comprising two domains (in the N-terminal to C-terminal direction, the “F2” and “F1” domains); the F2 domain comprising or consisting of an amino acid sequence having at least 70% sequence identity to positions 1-109 of SEQ ID NO: 1 or 2, such as at least 75%, 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, or preferably at least 95%, 96%, 97%, 98% or 99%, sequence identity to positions 1-109 of SEQ ID NO: 1 or 2; and the F1 domain comprising or consisting of an amino acid sequence having at least 70% sequence identity to positions 137-523 of SEQ ID NO: 1 or 2, such as at least 75%, 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, or preferably at least 95%, 96%, 97%, 98%, 99%, or 99.5% sequence identity to positions 137-523 of SEQ ID NO: 1 or 2. Alternatively, nucleic acids of the present disclosure may encode an RSV-F protein of the present disclosure, preferably according to (1), (2), (3) or (4), comprising an F2 domain and an F1 domain; the F2 domain comprising or consisting of an amino acid sequence having at least 70% sequence identity to positions 26-109 of SEQ ID NO: 1 or 2, such as at least 75%, 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, or preferably at least 95%, 96%, 97%, 98% or 99%, sequence identity to positions 26-109 of SEQ ID NO: 1 or 2; and the F1 domain comprising or consisting of an amino acid sequence having at least 70% sequence identity to positions 137-523 of SEQ ID NO: 1 or 2, such as at least 75%, 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, or preferably at least 95%, 96%, 97%, 98%, 99%, or 99.5% to positions 137-523 of SEQ ID NO: 1 or 2. RSV-F proteins of the present disclosure according to (4) preferably have such sequence identities (as defined in any of the three preceding paragraphs) according to SEQ ID NO: 1. Generally, nucleic acids (preferably RNA) of the present disclosure, and the RSV-F proteins encoded thereby, elicit a pre-fusion RSV-F-specific antibody response against RSV in vivo, e.g. an IgG antibody response (see, e.g. Example 6). Generally, nucleic acids of the present disclosure, and the RSV-F proteins encoded thereby, elicit a neutralising antibody response against RSV in vivo, e.g. against RSV-A (see, e.g. Example 6). Said neutralising antibody response may inhibit replication of RSV in the respiratory system of a subject Docket No.: 70280WO01 (such as in the lungs). Said neutralising antibody response may yield protective immunity against RSV in a subject. RSV-F proteins of the present disclosure are generally neither fused with, nor comprise, a green fluorescent protein (GFP). Nucleic acids of the present disclosure generally do not encode a GFP. In some embodiments, RSV-F proteins of the present disclosure do not comprise a S residue at position 552. In some embodiments, RSV-F proteins of the present disclosure do not comprise S residue at the position corresponding to position 552 of SEQ ID NO: 1 or 2, when the F1 and transmembrane domains of the RSV-F protein of the present disclosure is aligned with positions 137-549 of SEQ ID NO: 1 or 2. Nucleic acids of the present disclosure generally do not comprise a Xba1 restriction site. RSV-F proteins of the present disclosure generally neither comprise a cytoplasmic tail from (or derived from) vesicular stomatitis virus G protein (VSV-G), nor a portion of such a cytoplasmic tail. Nucleic acids of the present disclosure generally encode neither a sequence of a cytoplasmic tail from (or derived from) VSV-G, nor a portion of such a cytoplasmic tail. RSV-F proteins of the present disclosure are generally neither comprised within, nor located on the surface of, an RSV virion. RSV-F proteins of the present disclosure are generally neither comprised within, nor located on the surface of, a Hep-2 cell. In some embodiments, nucleic acids of the present disclosure do not encode an RSV-F protein (e.g. in the pre-fusion conformation when expressed) which is mutated relative to positions 1-513 of SEQ ID NO: 1; wherein the RSV-F protein comprises at least one mutation relative to positions 1-513 of SEQ ID NO: 1 in a region corresponding to positions 217-239 of SEQ ID NO:1; wherein the at least one mutation introduces, through substitution or insertion, a residue comprising a hydrogen bond donor and/or acceptor moiety in its side chain. In some embodiments, nucleic acids of the present disclosure do not encode an RSV-F protein (e.g. in the pre-fusion conformation when expressed) which is mutated relative to positions 1-513 of SEQ ID NO: 1; wherein the RSV-F protein comprises a substitution at position 228 of SEQ ID NO: 1 for K or A. In some embodiments, nucleic acids of the present disclosure do not encode an RSV-F protein (e.g. in the pre-fusion conformation when expressed) which is mutated relative to positions 1-513 of SEQ ID NO: 1 and comprises any of (a), (b), (c) and/or (d): (a) (ai) at least one mutation relative to positions 1-513 of SEQ ID NO: 1 in a region corresponding to positions 38-60 of SEQ ID NO:1, wherein the at least one mutation increases the hydrophobicity of the region relative to positions 38-60 of SEQ ID NO:1; and/or Docket No.: 70280WO01 (aii) at least one mutation relative to positions 1-513 of SEQ ID NO: 1 in a region corresponding to positions 296-318 of SEQ ID NO:1, wherein the at least one mutation increases the hydrophobicity of the region relative to positions 296-318 of SEQ ID NO:1, and/or introduces, through substitution or insertion, a residue selected from M, F, I and V into the region; (b) at least one mutation relative to positions 1-513 of SEQ ID NO: 1 in a region corresponding to positions 208-216 of SEQ ID NO:1, wherein the at least one mutation increases the hydrophobicity of the region relative to positions 208-216 of SEQ ID NO:1, and/or introduces, through substitution or insertion, a P residue into the region; (c) at least one mutation relative to positions 1-513 of SEQ ID NO: 1 in a region corresponding to positions 345-352 of SEQ ID NO:1, wherein the at least one mutation introduces, through substitution or insertion, a glycosylation site into the region; (d) at least one mutation relative to positions 1-513 of SEQ ID NO: 1 in a region corresponding to positions 345-352 of SEQ ID NO:1, wherein the at least one mutation introduces, through substitution or insertion, at least one residue selected from N, D, F, H, K, L, Q, R, T, W and Y into the region. In some embodiments, nucleic acids of the present disclosure do not encode an RSV-F protein (e.g. in the pre-fusion conformation when expressed) which is mutated relative to positions 1-513 of SEQ ID NO: 1 and comprises (a), (b) and (c): (a) (ai) at least one mutation relative to positions 1-513 of SEQ ID NO: 1 in a region corresponding to positions 38-60 of SEQ ID NO:1, wherein the at least one mutation increases the hydrophobicity of the region relative to positions 38-60 of SEQ ID NO:1; and/or (aii) at least one mutation relative to positions 1-513 of SEQ ID NO: 1 in a region corresponding to positions 296-318 of SEQ ID NO:1, wherein the at least one mutation increases the hydrophobicity of the region relative to positions 296-318 of SEQ ID NO:1, and/or introduces, through substitution or insertion, a residue selected from M, F, I and V into the region; (b) at least one mutation relative to positions 1-513 of SEQ ID NO: 1 in a region corresponding to positions 208-216 of SEQ ID NO:1, wherein the at least one mutation increases the hydrophobicity of the region relative to positions 208-216 of SEQ ID NO:1, and/or introduces, through substitution or insertion, a P residue into the region; and (c) at least one mutation relative to positions 1-513 of SEQ ID NO: 1 in a region corresponding to positions 345-352 of SEQ ID NO:1, wherein the at least one mutation introduces, through substitution or insertion, a glycosylation site into the region. Docket No.: 70280WO01 In some embodiments, nucleic acids of the present disclosure do not encode an RSV-F protein (e.g. in the pre-fusion conformation when expressed) which is mutated relative to positions 1-513 of SEQ ID NO: 1 and comprises (a), (b) and (d): (a) (ai) at least one mutation relative to positions 1-513 of SEQ ID NO: 1 in a region corresponding to positions 38-60 of SEQ ID NO:1, wherein the at least one mutation increases the hydrophobicity of the region relative to positions 38-60 of SEQ ID NO:1; and/or (aii) at least one mutation relative to positions 1-513 of SEQ ID NO: 1 in a region corresponding to positions 296-318 of SEQ ID NO:1, wherein the at least one mutation increases the hydrophobicity of the region relative to positions 296-318 of SEQ ID NO:1, and/or introduces, through substitution or insertion, a residue selected from M, F, I and V into the region; (b) at least one mutation relative to positions 1-513 of SEQ ID NO: 1 in a region corresponding to positions 208-216 of SEQ ID NO:1, wherein the at least one mutation increases the hydrophobicity of the region relative to positions 208-216 of SEQ ID NO:1, and/or introduces, through substitution or insertion, a P residue into the region; and (d) at least one mutation relative to positions 1-513 of SEQ ID NO: 1 in a region corresponding to positions 345-352 of SEQ ID NO:1, wherein the at least one mutation introduces, through substitution or insertion, at least one residue selected from N, D, F, H, K, L, Q, R, T, W and Y into the region. In some embodiments, nucleic acids of the present disclosure do not encode a recombinant RSV-F protein in the pre-fusion conformation, comprising at least one mutation relative to positions 1-513 of SEQ ID NO: 1, wherein the at least one mutation introduces neither a disulphide bond nor a P residue into said positions. Formats of nucleic acids The nucleic acid of the present disclosure may be DNA or RNA (including hybrids thereof), preferably RNA. DNA and RNA analogues, such as those containing modified backbones (e.g. peptide nucleic acids (PNAs) or phosphorothioates) or modified bases, are within the scope of the present disclosure. The nucleic acid may be linear, circular and/or branched, but will generally be linear. Typically, the nucleic acid will be in recombinant form, i.e. a form which does not occur in nature. The nucleic acid may be for the expression of an RSV-F protein of the present disclosure in vitro from a host cell (i.e. the nucleic acid is, or is part of, an expression vector). Suitable nucleic acid expression vectors (in particular, DNA expression vectors) can comprise, for example, (1) an origin of replication; (2) a selectable marker gene; (3) one or more expression control elements, such as a transcriptional control element (e.g., a promoter, an enhancer, or a terminator), and/or one or more translation signals; Docket No.: 70280WO01 and (4) a signal sequence or leader sequence for targeting to the secretory pathway in a selected host cell (e.g. those as detailed in the section entitled Preparing RSV-F proteins, above). In a preferred alternative embodiment, the nucleic acid is for the expression of an RSV-F protein of the present disclosure in vivo in a subject (i.e. the nucleic acid is, or is part of, a nucleic acid-based vaccine). In such preferred embodiments, in addition to a sequence encoding the RSV-F protein of the present disclosure, the nucleic acid may comprise one or more heterologous sequences, such as a sequence encoding a further protein (e.g. as detailed below) and/or a control sequence, in particular a promoter or an internal ribosome entry site. Nucleic acids of the present disclosure may be codon optimised. In some embodiments, nucleic acids of the present disclosure may be codon optimised for expression in human cells. Codon optimisation refers to the use of specific codons, which, while not altering the sequence of the expressed protein (given genetic code redundancy), may increase translation efficacy and/or half- life of the nucleic acid. Embodiments of codon optimised RNA are discussed in more detail in the subsection entitled RNA below. In some embodiments, nucleic acids of the present disclosure are in the form of a viral vector, such as a replicating or replication-deficient viral vector; including both DNA and RNA-based viral vectors. Suitable examples of viral vectors for encoding an RSV-F protein of the present disclosure include, for example: adenovirus vectors, such as replication-deficient or replication-competent adenovirus vectors; pox virus vectors, such as vaccinia virus vectors (e.g. modified vaccinia Ankara virus (MVA), NYVAC, avipox vectors, canarypox (e.g. ALVAC), and fowl pox virus (FPV)); Alphavirus vectors, such as Sindbis virus, Semlike Forest virus (SFV), Ross River virus, Venezuelan equine encephalitis (VEE) virus, and chimeras derived from Alphavirus vectors such as the foregoing; herpes virus vectors, such as cytomegalovirus (CMV)-derived vectors; arena virus vectors, such as lymphocytic choriomeningitis virus (LCMV) vectors; measles virus vectors; vesicular stomatitis virus vectors; pseudorabies virus vectors; adeno-associated virus vectors; retrovirus vectors; lentivirus vectors; and viral-like particles. In other embodiments, the nucleic acid is in the form of a DNA plasmid. In embodiments wherein the nucleic acid of the present disclosure is a viral vector, preferably the viral vector is an adenovirus vector, such as a replication-incompetent adenovirus type 26 (“Ad26”) or a replication-incompetent chimpanzee-adenovirus-155 (“ChAd155”), preferably a replication- incompetent Ad26. In such adenovirus vector embodiments, particular patient groups of interest (in which the adenovirus may be used in therapy, in particular vaccination) are infants and older adults (see section entitled Medical uses and methods of treatment, below). In such adenovirus vector embodiments, the adenovirus vector (preferably replication-incompetent Ad26) may also be co- formulated with an RSV-F protein (i.e. the protein per se) of the present disclosure, which may have the same, or a distinct, primary amino acid sequence to the RSV-F protein of the present disclosure encoded by the adenovirus. In such adenovirus vector embodiments, alternatively the adenovirus Docket No.: 70280WO01 vector (preferably replication-incompetent Ad26) may be co-formulated with a further RSV-F protein (i.e. the protein per se, that is not an RSV-F protein according to the present disclosure), such as an RSV-F protein with the p27 region deleted and optionally at least 2, 3, 4 or 5 mutations relative to wildtype RSV-F (such as N67I and S215P; N67I, S215P and E487Q; or K66E, N67I, I76V, S215P and D486N; in particular the latter set of five mutations). In such co-formulation embodiments, a particular patient group of interest (in which the co-formulation may be used in therapy, in particular vaccination) is older adults (see section entitled Medical uses and methods of treatment, below). In such older adults, the co-formulation may be administered as, or as part of, a prime-boost regimen, in particular involving administration of the co-formulation as both prime administration(s) and boost administration(s). The nucleic acid (preferably RNA) may encode an RSV-F protein of the present disclosure only (i.e. the nucleic acid encodes a single protein). Alternatively, the nucleic acid may encode multiple proteins, of which one is the RSV-F protein of the present disclosure. In some embodiments, the nucleic acid encodes at least (i) an RSV-F protein of the present disclosure; and (ii) at least one further protein. The at least one further protein may be a nanoparticle, e.g. a ferritin nanoparticle (e.g. which is encoded, along with the RSV-F protein of the present disclosure, by a single open reading frame, resulting in expression of a single polypeptide/protein). In preferred embodiments, the at least one further protein is an antigen; and as such may comprise, or may be, a viral, bacterial, fungal, parasitic, tumour, or allergenic (i.e. from, or derived from, an allergen) antigen; typically encoded by a separate open reading frame to the RSV-F protein of the invention. The at least one further protein will typically be a pathogen antigen. The at least one further protein will typically be an antigen that is a surface polypeptide e.g. a spike glycoprotein, a haemagglutinin, an adhesin or an envelope glycoprotein. In a particular embodiment, the at least one further protein is an antigen from, or derived from, a virus, in particular a virus causing respiratory disease, in particular a seasonal virus causing respiratory disease. In embodiments wherein the at least one further protein is an antigen from, or derived from, a virus, examples of such viruses include: Coronavirus, Orthomyxovirus, Pneumoviridae, Paramyxoviridae, Poxviridae, Picornavirus, Bunyavirus, Heparnavirus, Filovirus, Togavirus, Flavivirus, Pestivirus, Hepadnavirus, Rhabdovirus, Caliciviridae, Retrovirus, Reovirus, Parvovirus, Herpesvirus, Papovaviruses and Adenovirus. In a preferred embodiment, the at least one further protein detailed above is a further Pneumoviridae protein (in particular a Pneumoviridae antigen). Useful further Pneumoviridae proteins (in particular, antigens) can be from an Orthopneumovirus or Metapneumovirus, in particular human RSV or human Metapneumovirus (hMPV). Useful further hMPV antigens include e.g. the F, N, P, M, M2-1, and M2 antigens (in particular, the F antigen). Such hMPV proteins (in particular, antigens) may be from, or derived from, the A or B subtype. In a preferred embodiment, the nucleic acid is RNA encoding an RSV-F protein of the present disclosure in addition to an hMPV antigen (in particular, the F antigen). In such RNA embodiments, a preferred patient group (in which the RNA may be used in therapy, in Docket No.: 70280WO01 particular vaccination) is infants (see section entitled Medical uses and methods of treatment, below). Useful further human RSV antigens include e.g. the G, M1, M2-1, M2-2, P, L, N, NS1, NS2 and SH antigens, in addition to further RSV-F antigens, i.e. of distinct amino acid sequence to the RSV-F protein of the present disclosure encoded by the nucleic acid. Such further human RSV proteins (in particular, antigens) may be from, or derived from, the A or B subtype. In a particular embodiment, the nucleic acid is a viral vector (in particular, a poxvirus vector, in particular an MVA vector) encoding an RSV-F protein of the present disclosure in addition to a plurality of further RSV proteins (in particular, antigens); in particular at least 2, 3, or 4 further RSV proteins / antigens; in particular selected from G (from or derived from the A subtype: “G_A”), G (from or derived from the B subtype: “G_B”) N and either M2-1 or M2-2; in particular G_A, G_B, N and either of M2-1 or M2-2. In such viral vector embodiments, a particular patient group (in which the viral vector may be used in therapy, in particular vaccination) is older adults (see section entitled Medical uses and methods of treatment, below). In a preferred embodiment, the at least one further protein detailed above is a Coronavirus antigen. Useful Coronavirus antigens can be from a SARS coronavirus, in particular SARS-CoV2. Useful Coronavirus antigens (preferably SARS-CoV2 antigens) include the spike, M, E, HE, Nuclocapsid, Plpro and 3CLPro proteins, in particular spike protein. Preferably, the Coronavirus antigen is a SARS- CoV2 spike protein. Said SARS-CoV2 spike protein may be from any variant, e.g. Omicron (such as Omicron BA.1, BA.2, BA3, BA.4 or BA.5), Alpha, Epsilon, Eta, Theta, Kappa, Iota, Zeta, Mu, Lambda, Beta, Gamma, or Delta. Preferably, said SARS-CoV2 spike protein includes one or more mutations relative to the wild-type protein, in particular one or more (e.g. two) mutations to proline resides. Said one or more mutations may be introduced to stabilise said SARS-CoV2 spike protein in its pre-fusion conformation. In a preferred embodiment, the nucleic acid is RNA encoding an RSV-F protein of the present disclosure in addition to a Coronavirus antigen, e.g. as detailed above. In such RNA embodiments, a preferred patient group (in which the RNA may be used in therapy, in particular vaccination) is older adults (see section entitled Medical uses and methods of treatment, below). In another preferred embodiment, the at least one further protein detailed above is an Orthomyxovirus antigen. Useful Orthomyxovirus antigens can be from an influenza A, B or C virus. Useful Orthomyxovirus antigens (in particular influenza A, B or C virus antigens) include the haemagglutinin, neuraminidase and matrix M2 proteins, in particular haemagglutinin. Preferably, the Orthomyxovirus antigen is an influenza A virus haemagglutinin. Said influenza A virus hemagglutinin may be from any subtype e.g. H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15 or H16. In a preferred embodiment, the nucleic acid is RNA encoding an RSV-F protein of the present disclosure in addition to an Orthomyxovirus antigen, e.g. as detailed above. In such RNA embodiments, a preferred patient group (in which the RNA may be used in therapy, in particular vaccination) is older adults (see section entitled Medical uses and methods of treatment, below). In such RNA Docket No.: 70280WO01 embodiments, the RNA may encode (i) an RSV-F protein of the present disclosure, (ii) a Coronavirus antigen, e.g. as detailed above, and (iii) an Orthomyxovirus antigen, e.g. as detailed above. A plurality of nucleic acids of the present disclosure is, in particular, provided in purified or substantially purified form; that is, substantially free from other nucleic acids (e.g. free or substantially free from naturally-occurring nucleic acids, such as further nucleic acids expressed by a host cell). Said plurality of nucleic acids is generally at least 50% pure (by weight), such as at least 60%, 70%, 80%, 90%, or 95% pure (by weight). The present disclosure also provides, in a further independent aspect, a vector comprising one or more nucleic acids of the present disclosure. Nucleic acids encoding an RSV-F protein of the present disclosure may be delivered naked, or preferably in conjunction with a carrier (e.g. as detailed in the section entitled Carriers comprising a nucleic acid encoding an RSV-F protein, below). RNA In a preferred embodiment, the nucleic acid of the present disclosure is RNA. In the context of this section entitled RNA, “RNA” refers to an artificial (or, defined differently, recombinant) ribonucleic acid encoding an RSV-F protein of the present disclosure, which may be translated in a cell (i.e. mRNA). Preferably, the RNA is neither, nor comprised within, a viral vector or virus-based vaccine (such as a live-attenuated virus vaccine). RNA molecules can have various lengths but are typically 500-20,000 ribonucleotides long e.g.1000- 20,000, 1000-15,000, 1000-10,000, 1000-5000, 1000-3000, 1000-2500, 1000-2500 or 1000-2000 ribonucleotides long. The RNA can be non-self-replicating (also referred to as “conventional” RNA), or self-replicating; preferably non-self-replicating. In some embodiments, the RNA is self-replicating. Self-replicating RNA can be produced using replication elements derived from, e.g., alphaviruses, and substituting sequences encoding the structural viral proteins with that encoding at least an RSV-F protein of the present disclosure. A self- replicating RNA molecule is typically a positive-strand molecule which can be directly translated after delivery to a cell, and this translation provides an RNA-dependent RNA polymerase which then produces both antisense and sense transcripts from the delivered RNA. Thus, the delivered RNA leads to the production of multiple daughter RNAs. These daughter RNAs, as well as collinear subgenomic transcripts, may be translated themselves to provide in situ expression of the encoded protein (i.e. the RSV-F protein of the present disclosure); or may be transcribed to provide further transcripts with the same sense as the delivered RNA, which are translated to provide in situ expression of the encoded protein. The overall result of this sequence of transcriptions is substantial amplification in the number Docket No.: 70280WO01 of the introduced RNAs, and so the encoded RSV-F protein of the present disclosure (potentially in addition to further proteins as detailed above) becomes a major polypeptide product of the cells. In such embodiments wherein the RNA is self-replicating, it may encode (i) an RNA-dependent RNA polymerase which can transcribe RNA from the self-replicating RNA and (ii) an RSV-F protein of the present disclosure. The polymerase can be an alphavirus replicase e.g. comprising one or more of alphavirus proteins nsP1, nsP2, nsP3 and nsP4. Such alphavirus-based self-replicating RNA can use a replicase from, for example, a Sindbis virus, a Semliki forest virus, an eastern equine encephalitis virus (EEEV), or a Venezuelan equine encephalitis virus (VEEV). Mutant or wild-type virus sequences can be used e.g. the attenuated TC83 mutant of VEEV has been used for self-replicating RNA (see [18]). Thus, a self-replicating RNA encoding an RSV-F protein of the present disclosure may have two open reading frames. The first (5') open reading frame encodes a replicase, in particular an alphavirus replicase (e.g. as detailed above); the second (3') open reading frame encodes the RSV-F protein of the present disclosure. Further open reading frames may also be present, encoding (i) one or more further proteins (preferably one or more further antigens, e.g. as detailed above); and/or (ii) accessory polypeptides. Generally, the RNA comprises a 5’ cap, such as a 7-methylguanosine, which may be added via enzymatic means or a non-enzymatic reaction. The RNA may have the following exemplary 5’ caps: - a 7-methylguanosine linked 5’-to-5’ to the 5’ first ribonucleotide by a triphosphate bridge (also referred to as “Cap O”); - a 7-methylguanosine linked 5’-to-5’ to the 5’ first ribonucleotide by a triphosphate bridge, and wherein the first 5’ ribonucleotide comprises a 2’-methylated ribose (2’-O-Me) (also referred to as “Cap 1”); - a 7-methylguanosine linked 5’-to-5’ to the 5’ first ribonucleotides by a triphosphate bridge, and wherein the first and second 5’ ribonucleotides comprise a 2’-methylated ribose (2’-O-Me) (also referred to as “Cap 2”); - or a 7-methylguanosine linked 5’-to-5’ to the 5’ first ribonucleotides by a triphosphate bridge, and wherein the first, second and third 5’ ribonucleotides comprise a 2’-methylated ribose (2’- O-Me). In a preferred embodiment, the 5’ cap is a 7-methylguanosine linked 5’-to-5’ to the 5’ first ribonucleoside by a triphosphate bridge, and wherein the first 5’ ribonucleoside comprises a 2’- methylated ribose (2’-O-Me), e.g. the 5’ end of the RNA has the structure m7G(5')ppp(5')(2'OMeA)pG. Preferably, this cap is added non-enzymatically through the use of the following reagent: Docket No.: 70280WO01

Said reagent is sold as CLEANCAP Reagent AG (TRILINK BIOTECHNOLOGIES). In other embodiments, a cap may be added resulting in the 5’ end of the RNA having the structure m7(3'OMeG)(5')ppp(5')(2'OMeA)pG. This cap may be added non-enzymatically through the use of the following reagent:

Said reagent is sold as CLEANCAP Reagent AG (3’OMe) (TRILINK BIOTECHNOLOGIES) Generally, the RNA comprises a 3’ poly-adenosine (“poly-A”) tail, e.g. comprising 10-700 A ribonucleotides. The poly-A tail may comprise at least two non-contiguous stretches of A ribonucleotides (also referred to as a “split poly-A tail”), or a (in particular, only one) contiguous stretch of A ribonucleotides. The total number of A ribonucleotides (“As”) in at least two non- contiguous stretches may be, for example, 10-700, such as 10-600, 10-500, 20-500, 50-500, 70-500, 100-500, 20-400, 30-300, 40-200, 50-150, 70-120, 100-120, or, in particular, 100-120. The total number of As in a (in particular, only one) contiguous stretch may be, for example, 10-700; such as 10-600, 20-600 or in particular 40-600 (such as 50-600, 80-600, 80-550, 100-500; or 40-70, 50-65 or Docket No.: 70280WO01 55-65). Wherein at least two non-contiguous stretches of As are used, these may be of differing length. For example, a first stretch may be 10-150 As in length, such as 10-100, 10-50, 15-50, 20-50, 20-40, 25-40, or, in particular 25-35 As in length. For example, a second stretch may be 10-150 As in length, such as 10-150, 20-120, 30-100, 40-90, 50-90, 60-90, 65-90, 70-90, or, in particular, 80-90 As in length. The first stretch may be located 5’ or 3’ relative to the second stretch. However, in a particular embodiment, the first stretch is located 5’ relative to the second stretch. In a further particular embodiment, the polyA tail comprises, in the 5’ to 3’ direction, a first and a second non-contiguous stretch of As, that are 25-35 and 80-90 As in length respectively. In a further particular embodiment, the polyA tail comprises, in the 5’-3’ direction, a first and a second non-contiguous stretch of As, that are 25-35 and 65-90 As in length respectively. In a preferred embodiment, the polyA tail comprises, in the 5’-3’ direction, a first and a second non-contiguous stretch of As, that are 25-35 (e.g.28-32, 29- 31, about 30 or 30) and 25-45 (e.g. 25-40, 30-40, 35-40, 35-39, 36-38, about 37 or 37) As in length respectively. In some embodiments, the at least two non-contiguous stretches of As is from, or is part of, the 3’ untranslated region (UTR), e.g. as detailed below. The RNA preferably comprises (in addition to any 5' cap structure) one or more modified ribonucleotides, i.e. ribonucleotides that are modified in structure relative to standard A, C, G or U ribonucleotides. In other embodiments, the RNA does not comprise modified ribonucleotides, i.e. the RNA contains standard A, C, G or U ribonucleotides only (except for any 5’ cap structure, if present, e.g. as detailed above). In preferred embodiments wherein one or more modified ribonucleotides are used, said one or more modified ribonucleotides may be, or may comprise, N1-methylpseudouridine (“1mΨ”); pseudouridine (“Ψ”); N1-ethylpseudouridine; 2-methylthio-N6-(cis- hydroxyisopentenyl)adenosine; 2-methylthio-N6-methyladenosine; 2-methylthio-N6-threonyl carbamoyladenosine; N6-glycinylcarbamoyladenosine; N6-isopentenyladenosine; N6- methyladenosine (m6A); N6-threonylcarbamoyladenosine; 1,2'-O-dimethyladenosine; 1- methyladenosine; 2'-O-methyladenosine; 2'-O-ribosyladenosine (phosphate); 2-methyladenosine; 2- methylthio-N6 isopentenyladenosine; 2-methylthio-N6-hydroxynorvalyl carbamoyladenosine; 2'-O- methyladenosine; 2'-O-ribosyladenosine (phosphate); Isopentenyladenosine; N6-(cis- hydroxyisopentenyl)adenosine; N6,2'-O-dimethyladenosine; N6,2'-O-dimethyladenosine; N6,N6,2'- O-trimethyladenosine; N6,N6-dimethyladenosine; N6-acetyladenosine; N6- hydroxynorvalylcarbamoyladenosine; N6-methyl-N6-threonylcarbamoyladenosine; 2- methyladenosine; 2-methylthio-N6-isopentenyladenosine; 7-deaza-adenosine; N1-methyl-adenosine; N6,N6 (dimethyl)adenine; N6-cis-hydroxy-isopentenyl-adenosine; .alpha.-thio-adenosine; 2 (amino)adenine; 2 (aminopropyl)adenine; 2 (methylthio) N6 (isopentenyl)adenine; 2-(alkyl)adenine; 2-(aminoalkyl)adenine; 2-(aminopropyl)adenine; 2-(halo)adenine; 2-(halo)adenine; 2- (propyl)adenine; 2'-Amino-2'-deoxy-ATP; 2'-Azido-2'-deoxy-ATP; 2'-Deoxy-2'-a-aminoadenosine TP; 2'-Deoxy-2'-a-azidoadenosine TP; 6 (alkyl)adenine; 6 (methyl)adenine; 6-(alkyl)adenine; 6- (methyl)adenine; 7 (deaza)adenine; 8 (alkenyl)adenine; 8 (alkynyl)adenine; 8 (amino)adenine; 8 Docket No.: 70280WO01 (thioalkyl)adenine; 8-(alkenyl)adenine; 8-(alkyl)adenine; 8-(alkynyl)adenine; 8-(amino)adenine; 8- (halo)adenine; 8-(hydroxyl)adenine; 8-(thioalkyl)adenine; 8-(thiol)adenine; 8-azido-adenosine; aza adenine; deaza adenine; N6 (methyl)adenine; N6-(isopentyl)adenine; 7-deaza-8-aza-adenosine; 7- methyladenine; 1-Deazaadenosine TP; 2'Fluoro-N6-Bz-deoxyadenosine TP; 2'-OMe-2-Amino-ATP; 2'O-methyl-N6-Bz-deoxyadenosine TP; 2'-a-Ethynyladenosine TP; 2-aminoadenine; 2- Aminoadenosine TP; 2-Amino-ATP; 2'-a-Trifluoromethyladenosine TP; 2-Azidoadenosine TP; 2'-b- Ethynyladenosine TP; 2-Bromoadenosine TP; 2'-b-Trifluoromethyladenosine TP; 2-Chloroadenosine TP; 2'-Deoxy-2',2'-difluoroadenosine TP; 2'-Deoxy-2'-a-mercaptoadenosine TP; 2'-Deoxy-2'-a- thiomethoxyadenosine TP; 2'-Deoxy-2'-b-aminoadenosine TP; 2'-Deoxy-2'-b-azidoadenosine TP; 2'- Deoxy-2'-b-bromoadenosine TP; 2'-Deoxy-2'-b-chloroadenosine TP; 2'-Deoxy-2'-b-fluoroadenosine TP; 2'-Deoxy-2'-b-iodoadenosine TP; 2'-Deoxy-2'-b-mercaptoadenosine TP; 2'-Deoxy-2'-b- thiomethoxyadenosine TP; 2-Fluoroadenosine TP; 2-Iodoadenosine TP; 2-Mercaptoadenosine TP; 2- methoxy-adenine; 2-methylthio-adenine; 2-Trifluoromethyladenosine TP; 3-Deaza-3- bromoadenosine TP; 3-Deaza-3-chloroadenosine TP; 3-Deaza-3-fluoroadenosine TP; 3-Deaza-3- iodoadenosine TP; 3-Deazaadenosine TP; 4'-Azidoadenosine TP; 4'-Carbocyclic adenosine TP; 4'- Ethynyladenosine TP; 5'-Homo-adenosine TP; 8-Aza-ATP; 8-bromo-adenosine TP; 8- Trifluoromethyladenosine TP; 9-Deazaadenosine TP; 2-aminopurine; 7-deaza-2,6-diaminopurine; 7- deaza-8-aza-2,6-diaminopurine; 7-deaza-8-aza-2-aminopurine; 2,6-diaminopurine; 7-deaza-8-aza- adenine, 7-deaza-2-aminopurine; 2-thiocytidine; 3-methylcytidine; 5-formylcytidine; 5- hydroxymethylcytidine; 5-methylcytidine; N4-acetylcytidine; 2'-O-methylcytidine; 2'-O- methylcytidine; 5,2'-O-dimethylcytidine; 5-formyl-2'-O-methylcytidine; Lysidine; N4,2'-O- dimethylcytidine; N4-acetyl-2'-O-methylcytidine; N4-methylcytidine; N4,N4-Dimethyl-2'-OMe- Cytidine TP; 4-methylcytidine; 5-aza-cytidine; Pseudo-iso-cytidine; pyrrolo-cytidine; .alpha.-thio- cytidine; 2-(thio)cytosine; 2'-Amino-2'-deoxy-CTP; 2'-Azido-2'-deoxy-CTP; 2'-Deoxy-2'-a- aminocytidine TP; 2'-Deoxy-2'-a-azidocytidine TP; 3 (deaza) 5 (aza)cytosine; 3 (methyl)cytosine; 3- (alkyl)cytosine; 3-(deaza) 5 (aza)cytosine; 3-(methyl)cytidine; 4,2'-O-dimethylcytidine; 5 (halo)cytosine; 5 (methyl)cytosine; 5 (propynyl)cytosine; 5 (trifluoromethyl)cytosine; 5- (alkyl)cytosine; 5-(alkynyl)cytosine; 5-(halo)cytosine; 5-(propynyl)cytosine; 5- (trifluoromethyl)cytosine: 5-bromo-cytidine; 5-iodo-cytidine; 5-propynyl cytosine; 6-(azo)cytosine; 6- aza-cytidine; aza cytosine; deaza cytosine; N4 (acetyl)cytosine; 1-methyl-1-deaza-pseudoisocytidine; 1-methyl-pseudoisocytidine; 2-methoxy-5-methyl-cytidine: 2-methoxy-cytidine; 2-thio-5-methyl- cytidine; 4-methoxy-1-methyl-pseudoisocytidine; 4-methoxy-pseudoisocytidine; 4-thio-1-methyl-1- deaza-pseudoisocytidine; 4-thio-1-methyl-pseudoisocytidine; 4-thio-pseudoisocytidine; 5-aza- zebularine; 5-methyl-zebularine; pyrrolo-pseudoisocytidine; Zebularine; (E)-5-(2-Bromo- vinyl)cytidine TP; 2,2'-anhydro-cytidine TP hydrochloride; 2'Fluor-N4-Bz-cytidine TP; 2'Fluoro-N4- Acetyl-cytidine TP; 2'-O-Methyl-N4-Acetyl-cytidine TP; 2'O-methyl-N4-Bz-cytidine TP; 2'-a- Ethynylcytidine TP; 2'-a-Trifluoromethylcytidine TP; 2'-b-Ethynylcytidine TP; 2'-b- Trifluoromethylcytidine TP; 2'-Deoxy-2',2'-difluorocytidine TP; 2'-Deoxy-2'-a-mercaptocytidine TP; Docket No.: 70280WO01 2'-Deoxy-2'-a-thiomethoxycytidine TP; 2'-Deoxy-2'-b-aminocytidine TP; 2'-Deoxy-2'-b-azidocytidine TP; 2'-Deoxy-2'-b-bromocytidine TP; 2'-Deoxy-2'-b-chlorocytidine TP; 2'-Deoxy-2'-b-fluorocytidine TP; 2'-Deoxy-2'-b-iodocytidine TP; 2'-Deoxy-2'-b-mercaptocytidine TP; 2'-Deoxy-2'-b- thiomethoxycytidine TP; 2'-O-Methyl-5-(1-propynyl)cytidine TP; 3'-Ethynylcytidine TP; 4'- Azidocytidine TP; 4'-Carbocyclic cytidine TP; 4'-Ethynylcytidine TP; 5-(1-Propynyl)ara-cytidine TP; 5-(2-Chloro-phenyl)-2-thiocytidine TP; 5-(4-Amino-phenyl)-2-thiocytidine TP; 5-Aminoallyl-CTP; 5-Cyanocytidine TP; 5-Ethynylara-cytidine TP; 5-Ethynylcytidine TP; 5'-Homo-cytidine TP; 5- Methoxycytidine TP; 5-Trifluoromethyl-Cytidine TP; N4-Amino-cytidine TP; N4-Benzoyl-cytidine TP; Pseudoisocytidine; 7-methylguanosine; N2,2'-O-dimethylguanosine; N2-methylguanosine; Wyosine; 1,2'-O-dimethylguanosine; 1-methylguanosine; 2'-O-methylguanosine; 2'-O- ribosylguanosine (phosphate); 2'-O-methylguanosine; 2'-O-ribosylguanosine (phosphate); 7- aminomethyl-7-deazaguanosine; 7-cyano-7-deazaguanosine; Archaeosine; Methylwyosine; N2,7- dimethylguanosine; N2,N2,2'-O-trimethylguanosine; N2,N2,7-trimethylguanosine; N2,N2- dimethylguanosine; N2,7,2'-O-trimethylguanosine; 6-thio-guanosine; 7-deaza-guanosine; 8-oxo- guanosine; N1-methyl-guanosine; .alpha.-thio-guanosine; 2 (propyl)guanine; 2-(alkyl)guanine; 2'- Amino-2'-deoxy-GTP; 2'-Azido-2'-deoxy-GTP; 2'-Deoxy-2'-a-aminoguanosine TP; 2'-Deoxy-2'-a- azidoguanosine TP; 6 (methyl)guanine; 6-(alkyl)guanine; 6-(methyl)guanine; 6-methyl-guanosine; 7 (alkyl)guanine; 7 (deaza)guanine; 7 (methyl)guanine; 7-(alkyl)guanine; 7-(deaza)guanine; 7- (methyl)guanine; 8 (alkyl)guanine; 8 (alkynyl)guanine; 8 (halo)guanine; 8 (thioalkyl)guanine; 8- (alkenyl)guanine; 8-(alkyl)guanine; 8-(alkynyl)guanine; 8-(amino)guanine; 8-(halo)guanine; 8- (hydroxyl)guanine; 8-(thioalkyl)guanine; 8-(thiol)guanine; aza guanine; deaza guanine; N (methyl)guanine; N-(methyl)guanine; 1-methyl-6-thio-guanosine; 6-methoxy-guanosine; 6-thio-7- deaza-8-aza-guanosine; 6-thio-7-deaza-guanosine; 6-thio-7-methyl-guanosine; 7-deaza-8-aza- guanosine; 7-methyl-8-oxo-guanosine; N2,N2-dimethyl-6-thio-guanosine; N2-methyl-6-thio- guanosine; 1-Me-GTP; 2'Fluoro-N2-isobutyl-guanosine TP; 2'O-methyl-N2-isobutyl-guanosine TP; 2'-a-Ethynylguanosine TP; 2'-a-Trifluoromethylguanosine TP; 2'-b-Ethynylguanosine TP; 2'-b- Trifluoromethylguanosine TP; 2'-Deoxy-2',2'-difluoroguanosine TP; 2'-Deoxy-2'-a- mercaptoguanosine TP; 2'-Deoxy-2'-a-thiomethoxyguanosine TP; 2'-Deoxy-2'-b-aminoguanosine TP; 2'-Deoxy-2'-b-azidoguanosine TP; 2'-Deoxy-2'-b-bromoguanosine TP; 2'-Deoxy-2'-b- chloroguanosine TP; 2'-Deoxy-2'-b-fluoroguanosine TP; 2'-Deoxy-2'-b-iodoguanosine TP; 2'-Deoxy- 2'-b-mercaptoguanosine TP; 2'-Deoxy-2'-b-thiomethoxyguanosine TP; 4'-Azidoguanosine TP; 4'- Carbocyclic guanosine TP; 4'-Ethynylguanosine TP; 5'-Homo-guanosine TP; 8-bromo-guanosine TP; 9-Deazaguanosine TP; N2-isobutyl-guanosine TP; 1-methylinosine; Inosine; 1,2'-O-dimethylinosine; 2'-O-methylinosine; 7-methylinosine; 2'-O-methylinosine; Epoxyqueuosine; galactosyl-queuosine; Mannosylqueuosine; Queuosine; allyamino-thymidine; aza thymidine; deaza thymidine; deoxy- thymidine; 2'-O-methyluridine; 2-thiouridine; 3-methyluridine; 5-carboxymethyluridine; 5- hydroxyuridine; 5-methyluridine; 5-taurinomethyl-2-thiouridine; 5-taurinomethyluridine; Dihydrouridine; (3-(3-amino-3-carboxypropyl)uridine; 1-methyl-3-(3-amino-5- Docket No.: 70280WO01 carboxypropyl)pseudouridine; 1-methylpseduouridine; 1-methyl-pseudouridine; 2'-O-methyluridine; 2'-O-methylpseudouridine; 2'-O-methyluridine; 2-thio-2'-O-methyluridine; 3-(3-amino-3- carboxypropyl)uridine; 3,2'-O-dimethyluridine; 3-Methyl-pseudo-Uridine TP; 4-thiouridine; 5- (carboxyhydroxymethyl)uridine; 5-(carboxyhydroxymethyl)uridine methyl ester, 5,2'-O- dimethyluridine; 5,6-dihydro-uridine; 5-aminomethyl-2-thiouridine; 5-carbamoylmethyl-2'-O- methyluridine; 5-carbamoylmethyluridine; 5-carboxyhydroxymethyluridine; 5- carboxyhydroxymethyluridine methyl ester, 5-carboxymethylaminomethyl-2'-O-methyluridine; 5- carboxymethylaminomethyl-2-thiouridine; 5-carboxymethylaminomethyl-2-thiouridine; 5- caboxymethylaminomethyluridine; 5-carboxymethylaminomethyluridine; 5-Carbamoylmethyluridine TP; 5-methoxycaeoonylmethyl-2'-O-methyluridine; 5-methoxycarbonylmethyl-2-thiouridine; 5- methoxycarbonylmethyluridine; 5-methoxyuridine; 5-methyl-2-thiouridine; 5-methylaminomethyl-2- selenouridine; 5-methylaminomethyl-2-thiouridine; 5-methylaminomethyluridine; 5- Methyldihydrouridine; 5-Oxyacetic acid-Uridine TP; 5-Oxyacetic acid-methyl ester-Uridine TP; N1- methyl-pseudo-uridine; N1-ethyl-pseudo-uridine; uridine 5-oxyacetic acid; uridine 5-oxyacetic acid methyl ester; 3-(3-Amino-3-carboxypropyl)-Uridine TP; 5-(iso-Pentenylaminomethyl)-2-thiouridine TP; 5-(iso-Pentenylaminomethyl)-2'-O-methyluridine TP; 5-(iso-Pentenylaminomethyl)uridine TP; 5- propynyl uracil; .alpha.-thio-uridine; 1 (aminoalkylamino-carbonylethylenyl)-2(thio)-pseudouridine; 1 (aminoalkylaminocarbonylethylenyl)-2,4-(dithio)pseudouridine; 1 (aminoalkylaminocarbonylethylenyl)-4 (thio)pseudouridine; 1 (aminoalkylaminocarbonylethylenyl)- pseudouridine; 1 (aminocazbonylethylenyl)-2(thio)-pseudouridine; 1 (aminocarbonylethylenyl)-2,4- (dithio)pseudouridine; 1 (aminocarbonylethylenyl)-4 (thio)pseudouridine; 1 (aminocarbonylethylenyl)-pseudouridine; 1 substituted 2(thio)-pseudouridine; 1 substituted 2,4- (dithio)pseudouridine; 1 substituted 4 (thio)pseudouridine; 1 substituted pseudouridine; 1- (aminoalkylamino-carbonylethylenyl)-2-(thio)-pseudouridine; 1-Methyl-3-(3-amino-3- carboxypropyl) pseudouridine TP; 1-Methyl-3-(3-amino-3-carboxypropyl)pseudo-UTP; 1-Methyl- pseudo-UTP; 2 (thio)pseudouridine; 2' deoxy uridine; 2' fluorouridine; 2-(thio)uracil; 2,4- (dithio)psuedouracil; 2' methyl, 2'amino, 2'azido, 2'fluoro-guanosine; 2'-Amino-2'-deoxy-UTP; 2'- Azido-2'-deoxy-UTP; 2'-Azido-deoxyuridine TP; 2'-O-methylpseudouridine; 2' deoxy uridine; 2' fluorouridine; 2'-Deoxy-2'-a-aminouridine TP; 2'-Deoxy-2'-a-azidouridine TP; 2- methylpseudouridine; 3 (3 amino-3 carboxypropyl)uracil; 4 (thio)pseudouridine; 4- (thio)pseudouridine; 4-(thio)uracil; 4-thiouracil; 5 (1,3-diazole-1-alkyl)uracil; 5 (2- aminopropyl)uracil; 5 (aminoalkyl)uracil; 5 (dimethylaminoalkyl)uracil; 5 (guanidiniumalkyl)uracil; 5 (methoxycarbonylmethyl)-2-(thio)uracil; 5 (methoxycarbonyl-methyl)uracil; 5 (methyl) 2 (thio)uracil; 5 (methyl) 2,4 (dithio)uracil; 5 (methyl) 4 (thio)uracil; 5 (methylaminomethyl)-2 (thio)uracil; 5 (methylaminomethyl)-2,4 (dithio)uracil; 5 (methylaminomethyl)-4 (thio)uracil; 5 (propynyl)uracil; 5 (trifluoromethyl)uracil; 5-(2-aminopropyl)uracil; 5-(alkyl)-2-(thio)pseudouridine; 5-(alkyl)-2,4 (dithio)pseudouridine; 5-(alkyl)-4 (thio)pseudouridine; 5-(alkyl)pseudouridine; 5- (alkyl)uracil; 5-(alkynyl)uracil; 5-(allylamino)uracil; 5-(cyanoalkyl)uracil; 5- Docket No.: 70280WO01 (dialkylaminoalkyl)uracil; 5-(dimethylaminoalkyl)uracil; 5-(guanidiniumalkyl)uracil; 5-(halo)uracil; 5-(1,3-diazole-1-alkyl)uracil; 5-(methoxy)uracil; 5-(methoxycarbonylmethyl)-2-(thio)uracil; 5- (methoxycarbonyl-methyl)uracil; 5-(methyl) 2(thio)uracil; 5-(methyl) 2,4 (dithio)uracil; 5-(methyl) 4 (thio)uracil; 5-(methyl)-2-(thio)pseudouridine; 5-(methyl)-2,4 (dithio)pseudouridine; 5-(methyl)-4 (thio)pseudouridine; 5-(methyl)pseudouridine; 5-(methylaminomethyl)-2 (thio)uracil; 5- (methylaminomethyl)-2,4(dithio)uracil; 5-(methylaminomethyl)-4-(thio)uracil; 5-(propynyl)uracil; 5- (trifluoromethyl)uracil; 5-aminoallyl-uridine; 5-bromo-uridine; 5-iodo-uridine; 5-uracil; 6 (azo)uracil; 6-(azo)uracil; 6-aza-uridine; allyamino-uracil; aza uracil; deaza uracil; N3 (methyl)uracil; Pseudo- UTP-1-2-ethanoic acid; Pseudouridine; 4-Thio-pseudo-UTP; 1-carboxymethyl-pseudouridine; 1- methyl-1-deaza-pseudouridine; 1-propynyl-uridine; 1-taurinomethyl-1-methyl-uridine; 1- taurinomethyl-4-thio-uridine; 1-taurinomethyl-pseudouridine; 2-methoxy-4-thio-pseudouridine; 2- thio-1-methyl-1-deaza-pseudouridine; 2-thio-1-methyl-pseudouridine; 2-thio-5-aza-uridine; 2-thio- dihydropseudouridine; 2-thio-dihydrouridine; 2-thio-pseudouridine; 4-methoxy-2-thio-pseudouridine; 4-methoxy-pseudouridine; 4-thio-1-methyl-pseudouridine; 4-thio-pseudouridine; 5-aza-uridine; Dihydropseudouridine; (.+-.)1-(2-Hydroxypropyl)pseudouridine TP; (2R)-1-(2- Hydroxypropyl)pseudouridine TP; (2S)-1-(2-Hydroxypropyl)pseudouridine TP; (E)-5-(2-Bromo- vinyl)ara-uridine TP; (E)-5-(2-Bromo-vinyl)uridine TP; (Z)-5-(2-Bromo-vinyl)ara-uridine TP; (Z)-5- (2-Bromo-vinyl)uridine TP; 1-(2,2,2-Trifluoroethyl)-pseudo-UTP; 1-(2,2,3,3,3- Pentafluoropropyl)pseudouridine TP; 1-(2,2-Diethoxyethyl)pseudouridine TP; 1-(2,4,6- Trimethylbenzyl)pseudouridine TP; 1-(2,4,6-Trimethyl-benzyl)pseudo-UTP; 1-(2,4,6-Trimethyl- phenyl)pseudo-UTP; 1-(2-Amino-2-carboxyethyl)pseudo-UTP; 1-(2-Amino-ethyl)pseudo-UTP; 1-(2- Hydroxyethyl)pseudouridine TP; 1-(2-Methoxyethyl)pseudouridine TP; 1-(3,4-Bis- trifluoromethoxybenzyl)pseudouridine TP; 1-(3,4-Dimethoxybenzyl)pseudouridine TP; 1-(3-Amino- 3-carboxypropyl)pseudo-UTP; 1-(3-Amino-propyl)pseudo-UTP; 1-(3-Cyclopropyl-prop-2- ynyl)pseudouridine TP; 1-(4-Amino-4-carboxybutyl)pseudo-UTP; 1-(4-Amino-benzyl)pseudo-UTP; 1-(4-Amino-butyl)pseudo-UTP; 1-(4-Amino-phenyl)pseudo-UTP; 1-(4-Azidobenzyl)pseudouridine TP; 1-(4-Bromobenzyl)pseudouridine TP; 1-(4-Chlorobenzyl)pseudouridine TP; 1-(4- Fluorobenzyl)pseudouridine TP; 1-(4-Iodobenzyl)pseudouridine TP; 1-(4- Methanesulfonylbenzyl)pseudouridine TP; 1-(4-Methoxybenzyl)pseudouridine TP; 1-(4-Methoxy- benzyl)pseudo-UTP; 1-(4-Methoxy-phenyl)pseudo-UTP; 1-(4-Methylbenzyl)pseudouridine TP; 1-(4- Methyl-benzyl)pseudo-UTP; 1-(4-Nitrobenzyl)pseudouridine TP; 1-(4-Nitro-benzyl)pseudo-UTP; 1- (4-Nitro-phenyl)pseudo-UTP; 1-(4-Thiomethoxybenzyl)pseudouridine TP; 1-(4- Trifluoromethoxybenzyl)pseudouridine TP; 1-(4-Trifluoromethylbenzyl)pseudouridine TP; 1-(5- Amino-pentyl)pseudo-UTP; 1-(6-Amino-hexyl)pseudo-UTP; 1,6-Dimethyl-pseudo-UTP; 1-[3-(2-{2- [2-(2-Aminoethoxy)-ethoxy]-ethoxy}-ethoxy)-propionyl]pseudouri- dine TP; 1-{3-[2-(2- Aminoethoxy)-ethoxy]-propionyl} pseudouridine TP; 1-Acetylpseudouridine TP; I-Alkyl-6-(1- propynyl)-pseudo-UTP; 1-Alkyl-6-(2-propynyl)-pseudo-UTP; 1-Alkyl-6-allyl-pseudo-UTP; 1-Alkyl- 6-ethynyl-pseudo-UTP; 1-Alkyl-6-homoallyl-pseudo-UTP; 1-Alkyl-6-vinyl-pseudo-UTP; 1- Docket No.: 70280WO01 Allylpseudouridine TP; 1-Aminomethyl-pseudo-UTP; 1-Benzoylpseudouridine TP; 1- Benzyloxymethylpseudouridine TP; 1-Benzyl-pseudo-UTP; 1-Biotinyl-PEG2-pseudouridine TP; 1- Biotinylpseudouridine TP; 1-Butyl-pseudo-UTP; 1-Cyanomethylpseudouridine TP; 1- Cyclobutylmethyl-pseudo-UTP; 1-Cyclobutyl-pseudo-UTP; 1-Cycloheptylmethyl-pseudo-UTP; 1- Cycloheptyl-pseudo-UTP; 1-Cyclohexylmethyl-pseudo-UTP; 1-Cyclohexyl-pseudo-UTP; 1- Cyclooctylmethyl-pseudo-UTP; 1-Cyclooctyl-pseudo-UTP; 1-Cyclopentylmethyl-pseudo-UTP; 1- Cyclopentyl-pseudo-UTP; 1-Cyclopropylmethyl-pseudo-UTP; 1-Cyclopropyl-pseudo-UTP; 1-Ethyl- pseudo-UTP; 1-Hexyl-pseudo-UTP; 1-Homoallylpseudouridine TP; 1-Hydroxymethylpseudouridine TP; 1-iso-propyl-pseudo-UTP; 1-Me-2-thio-pseudo-UTP; 1-Me-4-thio-pseudo-UTP; 1-Me-alpha- thio-pseudo-UTP; 1-Methanesulfonylmethylpseudouridine TP; 1-Methoxymethylpseudouridine TP; 1-Methyl-6-(2,2,2-Trifluoroethyl)pseudo-UTP; 1-Methyl-6-(4-morpholino)-pseudo-UTP; 1-Methyl- 6-(4-thiomorpholino)-pseudo-UTP; 1-Methyl-6-(substituted phenyl)pseudo-UTP; 1-Methyl-6-amino- pseudo-UTP; 1-Methyl-6-azido-pseudo-UTP; 1-Methyl-6-bromo-pseudo-UTP; 1-Methyl-6-butyl- pseudo-UTP; 1-Methyl-6-chloro-pseudo-UTP; 1-Methyl-6-cyano-pseudo-UTP; 1-Methyl-6- dimethylamino-pseudo-UTP; 1-Methyl-6-ethoxy-pseudo-UTP; 1-Methyl-6-ethylcarboxylate-pseudo- UTP; 1-Methyl-6-ethyl-pseudo-UTP; 1-Methyl-6-fluoro-pseudo-UTP; 1-Methyl-6-formyl-pseudo- UTP; 1-Methyl-6-hydroxyamino-pseudo-UTP; 1-Methyl-6-hydroxy-pseudo-UTP; 1-Methyl-6-iodo- pseudo-UTP; 1-Methyl-6-iso-propyl-pseudo-UTP; 1-Methyl-6-methoxy-pseudo-UTP; 1-Methyl-6- methylamino-pseudo-UTP; 1-Methyl-6-phenyl-pseudo-UTP; 1-Methyl-6-propyl-pseudo-UTP; 1- Methyl-6-tert-butyl-pseudo-UTP; 1-Methyl-6-trifluoromethoxy-pseudo-UTP; 1-Methyl-6- trifluoromethyl-pseudo-UTP; 1-Morpholinomethylpseudouridine TP; 1-Pentyl-pseudo-UTP; 1- Phenyl-pseudo-UTP; 1-Pivaloylpseudouridine TP; 1-Propargylpseudouridine TP; 1-Propyl-pseudo- UTP; 1-propynyl-pseudouridine; 1-p-tolyl-pseudo-UTP; 1-tert-Butyl-pseudo-UTP; 1- Thiomethoxymethylpseudouridine TP; 1-Thiomorpholinomethylpseudouridine TP; 1- Trifluoroacetylpseudouridine TP; 1-Trifluoromethyl-pseudo-UTP; 1-Vinylpseudouridine TP; 2,2'- anhydro-uridine TP; 2'-bromo-deoxyuridine TP; 2'-F-5-Methyl-2'-deoxy-UTP; 2'-OMe-5-Me-UTP; 2'-OMe-pseudo-UTP; 2'-a-Ethynyluridine TP; 2'-a-Trifluoromethyluridine TP; 2'-b-Ethynyluridine TP; 2'-b-Trifluoromethyluridine TP; 2'-Deoxy-2',2'-difluorouridine TP; 2'-Deoxy-2'-a- mercaptouridine TP; 2'-Deoxy-2'-a-thiomethoxyuridine TP; 2'-Deoxy-2'-b-aminouridine TP; 2'- Deoxy-2'-b-azidouridine TP; 2'-Deoxy-2'-b-bromouridine TP; 2'-Deoxy-2'-b-chlorouridine TP; 2'- Deoxy-2'-b-fluorouridine TP; 2'-Deoxy-2'-b-iodouridine TP; 2'-Deoxy-2'-b-mercaptouridine TP; 2'- Deoxy-2'-b-thiomethoxyuridine TP; 2-methoxy-4-thio-uridine; 2-methoxyuridine; 2'-O-Methyl-5-(1- propynyl)uridine TP; 3-Alkyl-pseudo-UTP; 4'-Azidouridine TP; 4'-Carbocyclic uridine TP; 4'- Ethynyluridine TP; 5-(1-Propynyl)ara-uridine TP; 5-(2-Furanyl)uridine TP; 5-Cyanouridine TP; 5- Dimethylaminouridine TP; 5'-Homo-uridine TP; 5-iodo-2'-fluoro-deoxyuridine TP; 5- Phenylethynyluridine TP; 5-Trideuteromethyl-6-deuterouridine TP; 5-Trifluoromethyl-Uridine TP; 5- Vinylarauridine TP; 6-(2,2,2-Trifluoroethyl)-pseudo-UTP; 6-(4-Morpholino)-pseudo-UTP; 6-(4- Thiomorpholino)-pseudo-UTP; 6-(Substituted-Phenyl)-pseudo-UTP; 6-Amino-pseudo-UTP; 6- Docket No.: 70280WO01 Azido-pseudo-UTP; 6-Bromo-pseudo-UTP; 6-Butyl-pseudo-UTP; 6-Chloro-pseudo-UTP; 6-Cyano- pseudo-UTP; 6-Dimethylamino-pseudo-UTP; 6-Ethoxy-pseudo-UTP; 6-Ethylcarboxylate-pseudo- UTP; 6-Ethyl-pseudo-UTP; 6-Fluoro-pseudo-UTP; 6-Formyl-pseudo-UTP; 6-Hydroxyamino-pseudo- UTP; 6-Hydroxy-pseudo-UTP; 6-Iodo-pseudo-UTP; 6-iso-Propyl-pseudo-UTP; 6-Methoxy-pseudo- UTP; 6-Methylamino-pseudo-UTP; 6-Methyl-pseudo-UTP; 6-Phenyl-pseudo-UTP; 6-Phenyl-pseudo- UTP; 6-Propyl-pseudo-UTP; 6-tert-Butyl-pseudo-UTP; 6-Trifluoromethoxy-pseudo-UTP; 6- Trifluoromethyl-pseudo-UTP; Alpha-thio-pseudo-UTP; Pseudouridine 1-(4-methylbenzenesulfonic acid) TP; Pseudouridine 1-(4-methylbenzoic acid) TP; Pseudouridine TP 1-[3-(2-ethoxy)]propionic acid; Pseudouridine TP 1-[3-{2-(2-[2-(2-ethoxy)-ethoxy]-ethoxy)-ethoxy}]propionic acid; Pseudouridine TP 1-[3-{2-(2-[2-{2-(2-ethoxy)-ethoxy)-ethoxy}-ethoxy]-ethoxy}]propionic acid; Pseudouridine TP 1-[3-{2-(2-[2-ethoxy]-ethoxy)-ethoxy}]propionic acid; Pseudouridine TP 1-[3-{2- (2-ethoxy)-ethoxy}]propionic acid; Pseudouridine TP 1-methylphosphonic acid; Pseudouridine TP 1- methylphosphonic acid diethyl ester; Pseudo-UTP-N1-3-propionic acid; Pseudo-UTP-N1-4-butanoic acid; Pseudo-UTP-N1-5-pentanoic acid; Pseudo-UTP-N1-6-hexanoic acid; Pseudo-UTP-N1-7- heptanoic acid; Pseudo-UTP-N1-methyl-p-benzoic acid; Pseudo-UTP-N1-p-benzoic acid; Wybutosine; Hydroxywybutosine; Isowyosine; Peroxywybutosine; undermodified hydroxywybutosine; 4-demethylwyosine; 2,6-(diamino)purine; 1-(aza)-2-(thio)-3-(aza)-phenoxazin- 1-yl: 1,3-(diaza)-2-(oxo)-phenthiazin-1-yl; 1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 1,3,5-(triaza)-2,6- (dioxa)-naphthalene; 2 (amino)purine; 2,4,5-(trimethyl)phenyl; 2' methyl, 2'amino, 2'azido, 2'fluoro- cytidine; 2' methyl, 2'amino, 2'azido, 2'fluoro-adenine; 2'methyl, 2'amino, 2'azido, 2'fluoro-uridine; 2'- amino-2'-deoxyribose; 2-amino-6-Chloro-purine; 2-aza-inosinyl; 2'-azido-2'-deoxyribose; 2'fluoro-2'- deoxyribose; 2'-fluoro-modified bases; 2'-O-methyl-ribose; 2-oxo-7-aminopyridopyrimidin-3-yl; 2- oxo-pyridopyrimidine-3-yl; 2-pyridinone; 3 nitropyrrole; 3-(methyl)-7-(propynyl)isocarbostyrilyl; 3- (methyl)isocarbostyrilyl; 4-(fluoro)-6-(methyl)benzimidazole; 4-(methyl)benzimidazole; 4- (methyl)indolyl; 4,6-(dimethyl)indolyl; 5 nitroindole; 5 substituted pyrimidines; 5- (methyl)isocarbostyrilyl; 5-nitroindole; 6-(aza)pyrimidine; 6-(azo)thymine; 6-(methyl)-7- (aza)indolyl; 6-chloro-purine; 6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; 7-(aminoalkylhydroxy)-1-(aza)- 2-(thio)-3-(aza)-phenthiazin-1-yl; 7-(aminoalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl; 7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 7-(aminoalkylhydroxy)-1,3-(diaza)-2- (oxo)-phenthiazin-1-yl; 7-(aminoalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 7-(aza)indolyl; 7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)-phenoxazinl-yl; 7-(guanidiniumalkylhydroxy)- 1-(aza)-2-(thio)-3-(aza)-phenthiazin-1-yl; 7-(guanidiniumalkylhydroxy)-1-(aza)-2-(thio)-3-(aza)- phenoxazin-1-yl; 7-(guanidiniumalkylhydroxy)-1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 7- (guanidiniumalkyl-hydroxy)-1,3-(diaza)-2-(oxo)-phenthiazin-1-yl; 7-(guanidiniumalkylhydroxy)-1,3- (diaza)-2-(oxo)-phenoxazin-1-yl; 7-(propynyl)isocarbostyrilyl; 7-(propynyl)isocarbostyrilyl, propynyl-7-(aza)indolyl; 7-deaza-inosinyl; 7-substituted 1-(aza)-2-(thio)-3-(aza)-phenoxazin-1-yl; 7- substituted 1,3-(diaza)-2-(oxo)-phenoxazin-1-yl; 9-(methyl)-imidizopyridinyl; Aminoindolyl; Anthracenyl; bis-ortho-(aminoalkylhydroxy)-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; bis-ortho- Docket No.: 70280WO01 substituted-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; Difluorotolyl; Hypoxanthine; Imidizopyridinyl; Inosinyl; Isocarbostyrilyl; Isoguanisine; N2-substituted purines; N6-methyl-2-amino-purine; N6- substituted purines; N-alkylated derivative; Napthalenyl; Nitrobenzimidazolyl; Nitroimidazolyl; Nitroindazolyl; Nitropyrazolyl; Nubularine; O6-substituted purines; O-alkylated derivative; ortho- (aminoalkylhydroxy)-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; ortho-substituted-6-phenyl-pyrrolo- pyrimidin-2-on-3-yl; Oxoformycin TP; para-(aminoalkylhydroxy)-6-phenyl-pyrrolo-pyrimidin-2-on- 3-yl; para-substituted-6-phenyl-pyrrolo-pyrimidin-2-on-3-yl; Pentacenyl; Phenanthracenyl; Phenyl; propynyl-7-(aza)indolyl; Pyrenyl; pyridopyrimidin-3-yl; pyridopyrimidin-3-yl, 2-oxo-7-amino- pyridopyrimidin-3-yl; pyrrolo-pyrimidin-2-on-3-yl; Pyrrolopyrimidinyl; Pyrrolopyrizinyl; Stilbenzyl; substituted 1,2,4-triazoles; Tetracenyl; Tubercidine; Xanthine; Xanthosine-5'-TP; 2-thio-zebularine; 5- aza-2-thio-zebularine; 7-deaza-2-amino-purine; pyridin-4-one ribonucleoside; 2-Amino-riboside-TP; Formycin A TP; Formycin B TP; Pyrrolosine TP; 2'-OH-ara-adenosine TP; 2'-OH-ara-cytidine TP; 2'- OH-ara-uridine TP; 2'-OH-ara-guanosine TP; 5-(2-carbomethoxyvinyl)uridine TP; or N6-(19-Amino- pentaoxanonadecyl)adenosine TP. In some embodiments, the percentage of standard As substituted with A-substitutable modified nucleotide (e.g. those above) is at least: 0.1%, 0.5%, 0.8%, 1%, 2%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or at least 99.9%, or 100%. In some embodiments, the percentage of standard As substituted with m6A may be 0.1-5%, in particular 0.5- 2%, in particular 0.8-1.2%, such as about 1% (or 1%); in these embodiments the RNA may be circular RNA. Low substitution levels with m6A (e.g.1%) have been shown in inhibit innate immune activation [19]. In some embodiments, the percentage of standard Cs substituted with cytosine-substitutable modified nucleotide (e.g. those above) is at least: 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or at least 99.9%, or 100%. In some embodiments, the percentage of standard Gs substituted with G-substitutable modified nucleotide (e.g. those above) is at least: 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or at least 99.9%, or 100%. In preferred embodiments, the percentage of standard Us substituted with U-substitutable modified nucleotide (e.g. those above) is at least: 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or at least 99.9%, or preferably 100%; more preferably with 1mΨ and/or Ψ (even more preferably 1mΨ) . In a preferred embodiment, the one or more modified ribonucleotides detailed above is, or comprise, 1mΨ and/or Ψ, more preferably 1mΨ. In such embodiments, the RNA may comprise 1mΨ and/or Ψ, and neither standard U ribonucleotides nor other modified U ribonucleotides (i.e. there are no standard U nucleotides, nor modified U ribonucleotides other than 1mΨ and/or Ψ, in the RNA; i.e. 100% U substitution). In particular, the RNA may comprise 1mΨ and/or Ψ, and neither standard U ribonucleotides nor other modified ribonucleotides (i.e. there are no standard U nucleotides, nor modified ribonucleotides of any type - A, C, G or U substitutable - other than 1mΨ and/or Ψ, in the RNA; i.e. 100% U substitution with no other modified nucleotides being allowed). The RNA may Docket No.: 70280WO01 comprise Ψ, and neither standard U ribonucleotides nor other modified U ribonucleotides (i.e. 100% U substitution with Ψ). In particular, the RNA may comprise Ψ, and neither standard U ribonucleotides nor other modified ribonucleotides (i.e. 100% U substitution with Ψ with no other modified nucleotides being allowed). More preferably, the RNA comprises 1mΨ, and neither standard U ribonucleotides nor other modified U ribonucleotides (i.e.100% U substitution with 1mΨ). In an even more preferred embodiment, the RNA comprises 1mΨ, and neither standard U ribonucleotides nor other modified ribonucleotides (i.e.100% U substitution with 1mΨ with no other modified nucleotides being allowed). In the embodiments in this paragraph, “[may] comprise[s]... and neither [X]...nor [Y]” may be used interchangeably with the wording “[may] comprise[s]... and does not comprise... [X] and/or [Y] ”. Preferably, the RNA is codon-optimised. Codon optimisation may provide an elevated GC content, relative to non-codon optimised RNA encoding the same protein(s). The GC content (the percentage of all ribonucleotides (or, defined alternatively, all “nitrogenous bases”) in the RNA which are G or C) of the RNA may be at least 10%, such as at least 20%, 30%, 35% or at least 40%, preferably at least 45%, 46%, 47%, 48%, 49%, or at least 50%. The GC content of the RNA may be 10-70%, such as 20- 65%, 30-65% or 35-65%, preferably 40-60%, 45-55%, 46-53%, 47-51%, or 48-50%. The GC content of the RNA may be 30-70%, such as 40-70%, 45-70%, 50-70%, or 55-70%. Codon optimisation may provide an elevated C content relative to non-codon optimised RNA encoding the same protein(s). The percentage of C-optimisable codons in the RNA which have been substituted, as a result of codon optimisation, for a codon with greater C content (while encoding the same amino acid) may be least 30%, such as at least 40%, 50%, 55% or at least 60%, preferably at least 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72% or at least 72%; The percentage of C-optimisable codons in the RNA which have been substituted, as a result of codon optimisation, for a codon with greater C content (while encoding the same amino acid) may be 30-80%, such as 40-90%, 45-90%, 50-80%, 55-80% or 60-80%, preferably 65-75%, 66-75%, 67-75%, 68-75%, 69-75%, 70-74%, 71-74% or 72-74%. Generally, the RNA comprises a 5’ and/or a 3’ untranslated region (UTR), preferably both a 5’ and 3’ UTR; e.g. selected from the 5’and 3’ UTRs of RNA transcripts of the following genes (preferably the following human genes): beta-actin, albumin, ATP synthase beta subunit, fibroblast activation protein (“FAP”), H4 clustered histone 15 (“HIST2H4A”), glyceraldehyde-3-phosphate dehydrogenase, heat shock protein family A (Hsp70) member 8 gene,, interleukin-2 gene (“IL-2”), and transferrin. In some preferred embodiments, the RNA comprises a 5’ and a 3’ UTR selected from: - SEQ ID NO: 38 and 39, respectively, - SEQ ID NO: 40 and 41, respectively, - SEQ ID NO: 42 and 43, respectively, - SEQ ID NO: 44 and 45, respectively, Docket No.: 70280WO01 - SEQ ID NO: 46 and 47, respectively, and - RNA sequences at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or at least 99.5% identical to SEQ ID NO: 38, 40, 42, 44 or 46 (for the 5’ UTR) and RNA sequences at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or at least 99.5% identical to SEQ ID NO: 39, 41, 43, 45 or 47 (for the 3’ UTR) (in particular, the pairing of 5’ and 3’ UTRs having such identity to SEQ ID NO: 38 and 39, SEQ ID NO: 40 and 41, SEQ ID NO: 42 and 43, SEQ ID NO: 44 and 45, and SEQ ID NO: 46 and 47, respectively); with RNA sequences according to SEQ ID NO: 38 and 39 (and RNA sequences having such identity thereto, preferably at least 95% or greater) being more preferred. Both the 3’ and 5’ UTR may influence expression of the RSV-F protein of the present disclosure through a variety of mechanisms. Without wishing to be found by this theory, the 5’ UTR may affect the expression of at least the RSV-F protein of the present disclosure e.g. via pre-initiation complex regulation, closed-loop regulation, upstream open reading frame regulations (i.e. reinitiation), provision of internal ribosome entry sites, and provision of microRNA binding sites. Without wishing to be found by this theory, the 3’ UTR may affect the expression of at least the RSV-F protein of the present disclosure e.g. via providing regulation regions that post-transcriptionally influence expression; e.g. influencing translation efficiency, localisation of the RNA, stability of the RNA, polyadenylation, and circularization of the RNA. In one specific embodiment, the RNA is circular RNA. In a preferred embodiment, the RNA fulfils at least two, at least three, at least four, or at least five of the following criteria (for example, (a), (b), (d) and (f); (a), (b), (c), (d) and (f); or (a), (b), (d), (e) and (f): (a) is non-self-replicating; (b) is single stranded; (c) comprises a 5’ cap, which is a 7-methylguanosine linked 5’-to-5’ to the 5’ first ribonucleotide by a triphosphate bridge, and wherein the first 5’ ribonucleotide comprises a 2’-methylated ribose (2’-O-Me); (d) comprises a 3’poly-A tail; (e) comprises 1mΨ, and neither standard U ribonucleotides nor other modified ribonucleotides; (f) comprises a 5’ and a 3’ UTR. In another preferred embodiment, the RNA fulfils all of criteria (a) – (f), above. Docket No.: 70280WO01 Generally, the RNA will comprise, in the 5’ to 3’ direction: 5’ Cap, 5’ UTR, open reading frame encoding at least an RSV-F protein of the present disclosure, 3’UTR, and 3’ poly-A tail (in particular, the 5’ Caps; 5’ UTRs, 3’UTRs and 3’ poly-A tails as detailed above throughout this subsection). In preferred embodiments, the RNA comprises or consists of the sequence: SEQ ID NO: 49; or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 215A, 228K, K315I, 346Q, 348N, 445D, 455V and 459M (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); SEQ ID NO: 50; or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 215A, 228K, K315I, 346Q, 348N, 445D, 455V and 459M (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); SEQ ID NO: 53; or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 210H, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 455V and 459M (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); SEQ ID NO: 54; or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 210H, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 455V and 459M (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); SEQ ID NO: 57 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 103C, 148C, 190I, 486S (relative to a wild-type RSV- F sequence, e.g. SEQ ID NO: 1 or 2); SEQ ID NO: 58 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical thereto, preferably encoding an RSV-F protein of the present Docket No.: 70280WO01 disclosure comprising the substitutions 103C, 148C, 190I, 486S (relative to a wild-type RSV- F sequence, e.g. SEQ ID NO: 1 or 2); SEQ ID NO: 59 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 103C, 148C, 190I, 486S (relative to a wild-type RSV- F sequence, e.g. SEQ ID NO: 1 or 2); SEQ ID NO: 60 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 67I and 215P e.g. relative to (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); SEQ ID NO: 61 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 67I and 215P e.g. relative to (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); SEQ ID NO: 62 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 67I and 215P e.g. relative to (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); SEQ ID NO: 63 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 67I and 215P e.g. relative to (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); SEQ ID NO: 64 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 67I and 215P e.g. relative to (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); SEQ ID NO: 65 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, Docket No.: 70280WO01 99.9% or at least 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 67I and 215P e.g. relative to (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2) SEQ ID NO: 66 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 67I and 215P e.g. relative to (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); SEQ ID NO: 117 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 215A, 228K, 315I, 346Q, 445D, 455V, 459M, 486C and 490C relative to (and numbered according to) SEQ ID NO: 1 or 2, preferably further comprising the deletion Δ555-574 relative to (and numbered according to) SEQ ID NO: 1 or 2; SEQ ID NO: 140; or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 215A, 228K, 315I, 346Q, 445D, 455V, 459M, 486C and 490C relative to (and numbered according to) SEQ ID NO: 1 or 2, preferably further comprising the deletion Δ555-574 relative to (and numbered according to) SEQ ID NO: 1 or 2; SEQ ID NO: 91; or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 211N, 215A, 228K, 315I, 346Q, 348N, 445D, 455V, 459M, 486C and 490C relative to (and numbered according to) SEQ ID NO: 1 or 2, preferably further comprising the deletion Δ555-574 relative to (and numbered according to) SEQ ID NO: 1 or 2; or SEQ ID NO: 121 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or 99.94% identical thereto, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 215A, 228K, 315I, 346Q, 445D, 455V, 459M, 486C, 490C relative to (and numbered according to) SEQ ID NO: 1 or 2, preferably further comprising a linker sequence joining the F1 and F2 domains of the RSV-F protein which is Docket No.: 70280WO01 preferably a GS linker, preferably further comprising the deletion Δ555-574 relative to (and numbered according to) SEQ ID NO: 1 or 2. The present disclosure also provides, in a further independent aspect, a DNA construct (preferably a DNA plasmid) encoding an RNA sequence comprising or consisting of: any of SEQ ID NO: 49, 50, 53, 54 or 57-66, or any of the foregoing sequences having sequence identity to any of SEQ ID NO: 49, 50, 53, 54 or 57-66. In preferred embodiments, the RNA comprises an open reading frame (ORF) comprising or consisting of the sequence of: positions 32-1744 of SEQ ID NO: 49; or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 215A, 228K, K315I, 346Q, 348N, 445D, 455V and 459M (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); positions 32-1693 of SEQ ID NO: 50; or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 215A, 228K, K315I, 346Q, 348N, 445D, 455V and 459M (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); positions 32-1744 of SEQ ID NO: 53; or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 210H, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 455V and 459M (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); positions 32-1693 of SEQ ID NO: 54; or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 210H, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 455V and 459M (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); positions 32-1744 of SEQ ID NO: 57 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, Docket No.: 70280WO01 99.7%, 99.8%, 99.9% or at least 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 103C, 148C, 190I, 486S (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); positions 32-1693 of SEQ ID NO: 58 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 103C, 148C, 190I, 486S (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); positions 32-1678 of SEQ ID NO: 59 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 103C, 148C, 190I, 486S (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); positions 32-1753 of SEQ ID NO: 60 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 67I and 215P (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); positions 32-1744 of SEQ ID NO: 61 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 67I and 215P (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); positions 32-1738 of SEQ ID NO: 62 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 67I and 215P (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); positions 32-1723 of SEQ ID NO: 63 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 67I and 215P (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); Docket No.: 70280WO01 positions 32-1708 of SEQ ID NO: 64 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 67I and 215P (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); positions 32-1693 of SEQ ID NO: 65 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 67I and 215P (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); or positions 32-1678 of SEQ ID NO: 66 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably at least 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or at least 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 67I and 215P (relative to a wild-type RSV-F sequence, e.g. SEQ ID NO: 1 or 2); or positions 32-1693 of SEQ ID NO: 117 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 215A, 228K, 315I, 346Q, 445D, 455V, 459M, 486C and 490C relative to (and numbered according to) SEQ ID NO: 1 or 2, preferably further comprising the deletion Δ555-574 relative to (and numbered according to) SEQ ID NO: 1 or 2; positions 32-1693 of SEQ ID NO: 140 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 215A, 228K, 315I, 346Q, 445D, 455V, 459M, 486C and 490C relative to (and numbered according to) SEQ ID NO: 1 or 2, preferably further comprising the deletion Δ555-574 relative to (and numbered according to) SEQ ID NO: 1 or 2; positions 32-1693 of SEQ ID NO: 91 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 211N, 215A, 228K, 315I, 346Q, 348N, 445D, 455V, 459M, 486C and 490C relative to (and numbered according to) SEQ ID Docket No.: 70280WO01 NO: 1 or 2, preferably further comprising the deletion Δ555-574 relative to (and numbered according to) SEQ ID NO: 1 or 2; or positions 32-1693 of SEQ ID NO: 121 or an RNA sequence at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or preferably 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or 99.94% identical to said positions, preferably encoding an RSV-F protein of the present disclosure comprising the substitutions 55T, 152R, 215A, 228K, 315I, 346Q, 445D, 455V, 459M, 486C, 490C relative to (and numbered according to) SEQ ID NO: 1 or 2, preferably further comprising a linker sequence joining the F1 and F2 domains of the RSV-F protein which is preferably a GS linker, preferably further comprising the deletion Δ555-574 relative to (and numbered according to) SEQ ID NO: 1 or 2. The present disclosure also provides, in a further independent aspect, a DNA construct (preferably a DNA plasmid) encoding an RNA sequence comprising an ORF; said ORF comprising or consisting of the sequence of: the respective positions of any of SEQ ID NO: 49, 50, 53, 54 or 57-66 as recited in the foregoing paragraphs, or any of the foregoing sequences having sequence identity to the respective positions of any of SEQ ID NO: 49, 50, 53, 54 or 57-66 as recited in the foregoing paragraphs. The present disclosure also provides, in a further independent aspect, a vector comprising one or more RNAs of the present disclosure. The present disclosure also provides, in a further independent aspect, a vector comprising a DNA construct encoding one or more RNAs of the present disclosure. Nucleic acid (e.g. RNA) alignments may be performed, for example, visually, or by any well-known algorithm; e.g. using an NCBI BLAST algorithm such as “megablast”, e.g. on default settings (available at e.g. https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastn&BLAST_SPEC=GeoBlast&PAGE_TY PE=BlastSearch); or e.g. using the “Muscle” algorithm (see, e.g. [20], [21]), e.g. on default settings; with the Muscle algorithm being preferred . Corresponding nucleotide or ribonucleotide positions are easily identifiable to the skilled person, and can be identified by aligning the nucleotide or ribonucleotide sequences using any well-known method (such as visual or algorithm, e.g. as detailed above). The RNA can conveniently be prepared by in vitro transcription (IVT). IVT can use a (DNA) template created and propagated in plasmid form in bacteria, or created synthetically (for example by gene synthesis and/or polymerase chain-reaction (PCR) engineering methods). For instance, a DNA- dependent RNA polymerase (such as the bacteriophage T7, T3 or SP6 RNA polymerases) can be used to transcribe the replicating RNA from a DNA template. Appropriate capping and poly-A addition reactions can be used as required (although the poly-A tail is usually encoded within the DNA template). Docket No.: 70280WO01 Carriers comprising a nucleic acid Nucleic acids (especially RNA) by themselves and unprotected, may be degraded by the subject’s nucleases and may require a carrier to facilitate target cell entry. Accordingly, the present disclosure also provides a carrier comprising a nucleic acid (preferably RNA) encoding an RSV-F protein of the present disclosure. The carrier may be lipid-based (e.g. a lipid nanoparticle or cationic nanoemulsion), polymer-based (e.g. comprising polyamines, dendrimers and/or copolymers), peptide or protein-based (e.g. comprising protamine, a cationic cell-penetrating peptide, and/or an anionic peptide conjugated to a positively charged polymer), cell-based (e.g. antigen presenting cells, such as dendritic cells loaded with the nucleic acid), or virus-based (e.g. viral replicon particles). In particular embodiments, the carrier is non-virion, i.e. free or substantially free of viral capsid. In particular, lipid-based carriers provide a means to protect the nucleic acid (preferably RNA), e.g. through encapsulation, and deliver it to target cells for protein expression. In certain embodiments, the lipid-based carrier is, or comprises, a cationic nano-emulsion (“CNE”). CNEs and methods for their preparation are described in, for example, [22]. With a CNE, the nucleic acid (preferably RNA) which encodes the RSV-F protein of the present disclosure is complexed with a CNE particle, in particular comprising an oil core and a cationic lipid. The cationic lipid can interact with the negatively charged molecule, thereby anchoring the molecule to the emulsion particles. In a particular embodiment, a lipid-based carrier is a lipid inorganic nanoparticle (“LION”). LNPs In a preferred embodiment, nucleic acids (preferably RNA) are encapsulated in a lipid nanoparticle (LNP). Thus, in a preferred embodiment, the present disclosure also provides an LNP encapsulating a nucleic acid (preferably RNA) which encodes an RSV-F protein of the present disclosure. A plurality of such LNPs will be part of a composition (e.g. a pharmaceutical composition as detailed in the section entitled Pharmaceutical compositions below) comprising free and/or encapsulated nucleic acid (preferably RNA), and in some embodiments the LNPs encapsulate at least: 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97.0%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98.0%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99.0%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or at least 100% of the total number of nucleic acid (preferably RNA) molecules in the composition. At least 80% of the LNPs in the composition may be 20-200 nm, 40-190 nm, 60-180 nm or, in particular, 80-160 nm in diameter. In a particular embodiment, substantially all, or all, LNPs in the composition are 20-200 nm, 40-190 nm, 60-180 nm or, in particular, 80-160 nm in diameter. The LNP can comprise multilamellar vesicles (MLV), small uniflagellar vesicles (SUV), or large unilamellar vesicles (LUV). Docket No.: 70280WO01 The amount of nucleic acid (preferably RNA) per LNP can vary, and the number of individual nucleic acid molecules per LNP can depend on the characteristics of the particle being used. For RNA molecules, in general, an LNP may include 1-500 RNA molecules, e.g. <200, <100, <50, <20, <10, <5, or 1-4. Generally, an LNP includes fewer than 10 different species of RNA e.g. fewer than 5, 4, 3, or 2 different species. Preferably the LNP includes a single RNA species (i.e. all RNA molecules in the particle have the same sequence). LNPs according to the present disclosure may be formed from a single lipid (e.g. a cationic lipid) or, in particular, from a mixture of lipids. In particular, the mixture comprises various classes of lipids, such as: (a) a mixture of cationic lipids and sterols, (b) a mixture of cationic lipids and neutral lipids, (c) a mixture of cationic lipids and polymer-conjugated lipids, (d) a mixture of cationic lipids, sterols and polymer-conjugated lipids, or (e) a mixture of cationic lipids, neutral lipids and polymer-conjugated lipids; or preferably: (f) a mixture of cationic lipids, sterols and neutral lipids; or more preferably: (g) a mixture of cationic lipids, neutral lipids, sterols and polymer-conjugated lipids. Further classes of lipids, such as anionic lipids, may also be present in a mixture of lipids. The cationic lipid may have a pKa of 5.0-10.0, 5.0-9.0, 5.0-8.5, preferably 5.0-8.0, 5.0-7.9, or 5.0-7.8, 5.0-7.7, or more preferably 5.0-7.6. The pKa of the cationic lipid is distinct to the pKa of the LNP as a whole (sometimes called “apparent pKa”). pKa may be determined via any well-known method, such as via a toluene nitrosulphonic acid (TNS) fluorescence assay or acid base titration; preferably a TNS fluorescence assay; more preferably performed according to Example 7. The cationic lipid preferably comprises a tertiary or quaternary amine group, more preferably a tertiary amine group. Exemplary cationic lipids comprising tertiary amine groups include: 1,2-dilinoleyoxy- 3-(dimethylamino)acetoxypropane (DLin-DAC), 1,2-dilinoleyoxy-3morpholinopropane (DLin-MA), 1,2-dilinoleoyl-3-dimethylaminopropane (DLinDAP), 1,2-dilinoleylthio-3-dimethylaminopropane (DLin-S-DMA), 1-linoleoyl-2-linoleyloxy-3dimethylaminopropane (DLin-2-DMAP), 1,2- dilinoleyloxy-3-trimethylaminopropane chloride salt (DLin-TMA.Cl), 1,2-dilinoleoyl-3- trimethylaminopropane chloride salt (DLin-TAP.Cl), 1,2-dilinoleyloxy-3-(N- Docket No.: 70280WO01 methylpiperazino)propane (DLin-MPZ), 3-(N,Ndilinoleylamino)-1,2-propanediol (DLinAP), 3-(N,N- dioleylamino)-1,2-propanediol (DOAP), 1,2-dilinoleyloxo-3-(2-N,N-dimethylamino)ethoxypropane (DLin-EG-DMA), and 2,2-dilinoleyl-4-dimethylaminomethyl[1,3]-dioxolane (DLin-K-DMA), 2,2- dilinoleyl-4-(2-dimethylaminoethyl)[1,3]-dioxolane (DLin-KC2-DMA); dilinoleyl-methyl-4- dimethylaminobutyrate (DLin-MC3-DMA); or MC3 (see, e.g. [23]). In some embodiments, the cationic lipid has the structure of lipid RV28, RV31, RV33, RV37, RV39 RV42, RV44, RV73, RV75, RV81, RV84, RV85, RV86, RV88, RV91, RV92, RV93, RV94, RV95, RV96, RV97, RV99 or RV101, as disclosed in [24]. In a further embodiment, the cationic lipid has the structure:

In a preferred embodiment, the cationic lipid has the structure:

(also referred to as lipid RV39). In another preferred embodiment, the cationic lipid has the structure: Docket No.: 70280WO01

In another preferred embodiment, the cationic lipid has the structure:

The lipids in the LNP may comprise (in mole %) 20-80, 25-75, 30-70, or 35-65%, preferably 30-60, 40-55 or 40-50% cationic lipid; such as about 40% (or 40%), about 42% (or 42%), about 44% (or 44%), about 46% (or 46%) or about 48% (or 48%) cationic lipid. The lipids in the LNP may comprise (in mole %) at least 20, 25 or at least 35%, or preferably at least 40% cationic lipid. The lipids in the LNP may comprise (in mole %) no more than 80, 70 or no more than 60% or preferably no more than 50% cationic lipid. The molar ratio of protonatable nitrogen atoms in the LNP’s cationic lipids to phosphates in the nucleic acid, preferably RNA (a.k.a “N:P” ratio), may be in the range of (including the endpoints) 1:1-20:1, 2:1-10:1, 3:1-9:1, or 4:1-8:1; preferably 4.5:1-7.5:1, 4.5:1-6.5:1 or 5.0:1-6.5:1. The polymer-conjugated lipid is preferably a PEGylated lipid. In an LNP, the PEGs of such PEGylated lipids may have a weight average molecular weight of 0.5-11.0 kDa; such as 0.5-8.0, 0.8-8.0, 0.8-7.0, 0.8-6.0, 0.8-5.0, 0.8-4.0, 1.0-4.0 or 1.0-3.5 kDa, preferably 1.0-3.0, 1.2-2.8, 1.4-2.6, 1.5-2.5, 1.6-2.4, or 1.7-2.3 kDa, or more preferably 1.8-2.2, 1.9-2.1, about 2.0 (or 2.0 kDa). Alternatively, in an LNP, the PEGs of such PEGylated lipids may have a number average molecular weight of 0.5-11.0 kDa; such as 0.5-8.0, 0.8-8.0, 0.8-7.0, 0.8-6.0, 0.8-5.0, 0.8-4.0, 1.0-4.0 or 1.0-3.5 kDa, preferably 1.0-3.0, Docket No.: 70280WO01 1.2-2.8, 1.4-2.6, 1.5-2.5, 1.6-2.4, or 1.7-2.3 kDa, or more preferably 1.8-2.2, 1.9-2.1, about 2.0 (or 2.0 kDa). The PEGylated lipid may have the structure:

Exemplary PEGylated lipids include 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide and 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000, 1,2-dimyristoyl-sn-glycero-2- phosphoethanolamine-N-[methoxy(polyethylene glycol)] and 1,2-dimyristoyl-rac-glycerol-3- methoxypolyethylene glycol. Preferably, the PEGylated lipid is 2-[(polyethylene glycol)-2000]-N,N- ditetradecylacetamide or 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000. The lipids in the LNP may comprise (in mole %) 0.1-8.0, 0.4-7.0, 0.6-6.0, 0.8-4.0 or 0.8-3.5%, preferably 1.0-3.0% polymer-conjugated lipid (preferably PEGylated lipid); such as about 1.0 (or 1.0%), about 1.5% (or 1.5%), about 2.0% (or 2.0%) or about 2.5% (or 2.5%) polymer-conjugated lipid (preferably PEGylated lipid). The lipids in the LNP may comprise (in mole %) at least 0.1, 0.5 or at least 0.8%, or preferably at least 1% polymer-conjugated lipid (preferably PEGylated lipid). The lipids in the LNP may comprise (in mole %) no more than 8.0, 6.0 or 4.0% or preferably no more than 3.0% polymer-conjugated lipid (preferably PEGylated lipid). Preferably, the neutral lipid is 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) or 1,2-dioleoyl-sn- glycero-3-phosphoethanolamine (DOPE), although other neutral lipids available to the skilled person may also be used. The lipids in the LNP may comprise (in mole %) 0-15.0, 0.1-15.0, 2.0-14.0, 5.0-13.0, 6.0-12.0 or 7.0- 11.0%, preferably 8.0-11.0% or 9.0-11.0% neutral lipid; such as about 9.4% (or 9.4%), about 9.6% (or 9.6%), about 9.8% (or 9.8%) or about 10.0% (or 10%) neutral lipid. The lipids in the LNP may comprise (in mole %) at least 0.1, 5.0 or at least 7.0%, or preferably at least 8.0% or at least 9.0% neutral lipid. The lipids in the LNP may comprise (in mole %) no more than 15.0, 13.0 or no more than 12.0%, or preferably no more than 11.0% neutral lipid. Exemplary sterols include cholesterol, cholesterol sulfate, desmosterol, stigmasterol, lanosterol, 7- dehydrocholesterol, dihydrolanosterol, symosterol, lathosteriol, 14-demethyl-lanosterol, 8(9)- dehydrocholesterol, 8(14)-dehydrocholesterol, 14-demethyl-14-dehydrolanosterol (FF-MAS), diosgenin, dehydroepiandrosterone sulfate (DHEA sulfate), dehydroepiandrosterone, sitosterol, Docket No.: 70280WO01 lanosterol-95, 4,4-dimethyl(d6)-cholest-8(9), 14-dien-3β-ol (dihydro-FF-MAS-d6), 4,4-dimethyl(d6)- cholest-8(9)-en-3β-ol (dihydro T-MAS-d6), zymostenol, sitostanol, campestanol, camperstanol, 7- dehydrodesmosterol, pregnenolone, 4,4-dimethyl-cholest-8(9)-en-3β-ol (dihyrdro T-MAS), Δ5- avensterol, brassicasterol, dihydro FF-MAS, 24-methylene cholesterol, oxysterols, deuterated sterols, fluorinated sterols, sulfonated sterols, phosphorylated sterols, A-ring substituted sterols, cholest-5-ene- 3ß,4ß-diol, 5α-cholestan-3ß-ol, 4-cholesten-3-one, cholesta-8(9),24-dien-3-one, cholesta-8(9),24- dien-3-one, 2,2,3,4,4-pentadeuterio-5a-cholestan-3ß-ol, cholesteryl phosphocholine, cholesteryl-d7 pentadecanoate, cholesteryl-d7 palmitate, B-ring substituted sterols, cholestanol, 5ß,6ß-epoxy-d7, 3ß- hydroxy-5-cholestene-7-one, 6α-hydroxy-5α-cholestane, cholestanol, 5α,6α-epoxy, cholest-5-en- 3ß,7α-diol, cholest-5-en-3ß,7ß-diol, cholestanol, 5α,6α-epoxy-d7, Δ5,7-cholesterol, cholesta-5,8(9)- dien-3ß-ol, cholesta-5,8(14)-dien-3ß-ol, 7α-hydroxy-4-cholesten-3-one, zymostenol-d7, zymostenol, 7-dehydrodesmosterol, 3b,5a-dihydroxy-cholestan-6-one, D-ring substituted sterols, 3ß-hydroxy-5α- cholest-8(14)-en-15-one, 3ß-hydroxy-5α-cholestane-15-one, 5α-cholest-8(14)-ene-3ß,15α-diol, 5α- cholest-8(14)-ene-3ß,15ß,-diol, lanosterol-95, 5α-7,24-cholestadiene, 14-dehydro zymostenol, ergosta-5,7,9(11),22-tetraen-3ß-ol, cholest-5-ene-3ß,25-diol, cholest-(25R)-5-ene-3ß,27-diol, 24(R/S),25-epoxycholesterol, 24(S),25-epoxycholesterol, 24(R/S),25-epoxycholesterol-d6, cholest-5- ene-3ß,22(S)-diol, cholest-5-ene-3ß,22(R)-diol, cholest-5-ene-3ß,24(S)-diol, cholest-5-ene-3ß,24(R)- diol, 27-hydroxy-4-cholesten-3-one, campestanol, N,N-dimethyl-3ß-hydroxycholenamide, 25,27- dihydroxycholesterol, N,N-dimethyl-3ß-hydroxycholenamide, 25,27-dihydroxycholesterol, 5- cholestene-3β,20α-diol, 24S,25-epoxy-5α-cholest-8(9)-en-3β-ol, 24(S/R),25-epoxylanost-8(9)-en-3β- ol, 7-keto-27-hydroxycholesterol, 7α,27-dihydroxy-4-cholesten-3-one, 7α,27-dihydroxycholesterol, 7ß,27-dihydroxycholesterol, 5α,6ß-dihydroxycholestanol, 7α,25-dihydroxycholesterol, 7β,25- dihydroxycholesterol, 7α,24(S)-dihydroxycholesterol, 7α,24(S)-dihydroxy-4-cholesten-3-one, 7-keto- 25-hydroxycholesterol, 7α,24S,27-trihydroxycholesterol, dihydrotestosterone, testosterone, estrone, estrogen, estradiol, corticosterone, cortisol, or 24S,27-dihydroxycholesterol. Preferably, the sterol is cholesterol or a cholesterol-based lipid (e.g. any of those provided in the foregoing paragraph). The lipids in the LNP may comprise (in mole %) 20-80, 25-80, 30-70, 30-60, 35-60 or 40-60%, preferably 40-50% or 41-49% sterol; such as about 42% (or 42%), about 43% (or 43%), about 44% (or 44%), about 46% (or 46%), or about 48% (or 48%) sterol. The lipids in the LNP may comprise (in mole %) at least 20, 30 or at least 35%, or preferably at least 40% or at least 41% sterol. The lipids in the LNP may comprise (in mole %) no more than 80, 70 or no more than 60%, or preferably no more than 50% sterol. Docket No.: 70280WO01 The lipids in the LNP may have the following mole % in combination: 30-60% cationic lipid (such as 35-55%, or preferably 40-50%), 35-70% sterol (such as 40-55%, or preferably 41-49%), 0.8-4.0% polymer-conjugated lipid (such as 0.8-3.5%, or preferably 1.0-3.0%), and 0-15% neutral lipid (such as 6.0-12.0% or preferably 8.0-11.0%). Such LNPs encapsulating nucleic acids (preferably RNA) may be formed by admixing a first solution comprising the nucleic acids with a second solution comprising lipids which form the LNP. The admixing may be performed by any suitable means available to the skilled person, e.g. a T-mixer, microfluidics, or an impinging jet mixer. Admixing may be followed by filtration to obtain a desirable LNP size distribution (e.g. those as detailed above in this subsection). The filtration may be performed by any suitable means available to the skilled person, e.g. tangential-flow filtration or cross-flow filtration. According, in a further independent aspect, the present disclosure provides a method of preparing an LNP encapsulating a nucleic acid (preferably RNA) of the present disclosure, comprising admixing a first solution comprising the nucleic acid and a second solution comprising lipids which form the LNP (e.g using the means as set out in the foregoing paragraph); and optionally filtering the obtained admixture (e.g. using the means as set out in the foregoing paragraph). Pharmaceutical compositions In a further independent aspect, the present disclosure also provides a pharmaceutical composition comprising a nucleic acid (preferably RNA), RSV-F protein and/or carrier (preferably lipid nanoparticle) of the present disclosure. Such compositions typically further comprise a pharmaceutically acceptable excipient. Pharmaceutically acceptable excipients are well-known in the art, see, e.g. [25]. Such compositions are generally for immunising subjects against disease, preferably against RSV. Accordingly, pharmaceutical compositions of the present disclosure are generally considered vaccine compositions or immunogenic compositions. Pharmaceutical compositions of the present disclosure may comprise the nucleic acid (preferably RNA), RSV-F protein and/or carrier (preferably lipid nanoparticle) in plain water (e.g. water for injection “w.f.i.”) or in a buffer e.g. a phosphate buffer, a Tris buffer, a borate buffer, a succinate buffer, a histidine buffer, or a citrate buffer. Buffer salts will typically be included in the 5-20mM range. Pharmaceutical compositions of the present disclosure may have a pH between 5.0 and 9.5 e.g. between 6.0 and 8.0. Pharmaceutical compositions of the present disclosure compositions may include sodium salts (e.g. sodium chloride) to give tonicity. A concentration of 10±2 mg/mL NaCl is typical, e.g. about 9 mg/mL (or 9 mg/mL).. Docket No.: 70280WO01 Pharmaceutical compositions of the present disclosure may include metal ion chelators (in particular, in embodiments wherein such compositions comprise RNA). These can prolong RNA stability by removing ions which can accelerate phosphodiester hydrolysis. Thus, such compositions may include one or more of EDTA, EGTA, BAPTA, pentetic acid, etc.. Such chelators are typically present at between 10-500 μΜ e.g.0.1 mM. A citrate salt, such as sodium citrate, can also act as a chelator, while advantageously also providing buffering activity. Pharmaceutical compositions of the present disclosure may have an osmolality of between 200 mOsm/kg and 400 mOsm/kg, e.g. between 240-360 mOsm/kg, or between 290-310 mOsm/kg. Pharmaceutical compositions of the present disclosure may include one or more preservatives, such as thiomersal or 2-phenoxyethanol. Mercury-free compositions are preferred, and preservative-free vaccines can be prepared. Pharmaceutical compositions of the present disclosure may be aseptic or sterile. Pharmaceutical compositions of the present disclosure may be non-pyrogenic e.g. containing <1 EU (endotoxin unit, a standard measure) per dose, and preferably <0.1 EU per dose. Pharmaceutical compositions of the present disclosure may be gluten free. Pharmaceutical compositions of the present disclosure may be prepared in unit dose form. In some embodiments a unit dose may have a volume of between 0.1 -1.0 mL e.g. about 0.5mL (or 0.5mL). Pharmaceutical compositions of the present disclosure may be prepared as injectables, either as solutions or suspensions. The composition may be prepared for pulmonary administration e.g. by an inhaler, using a fine spray. The composition may be prepared for nasal, aural or ocular administration e.g. as spray or drops. Injectables for intramuscular administration are typical. Pharmaceutical compositions of the present disclosure comprise an immunologically effective amount of RSV-F protein. nucleic acid (preferably RNA) and/or carrier (preferably lipid nanoparticle), as well as any other components, as needed. Herein, “effective amount” and “immunologically effective amount” are used interchangeably. By “immunologically effective amount”, it is meant that the administration of that amount to an individual, either in a single dose or as part of a series, is effective for treatment or prevention, preferably prevention of RSV. This amount varies depending upon the health and physical condition of the individual to be treated, age, the taxonomic group of individual to be treated (e.g. nonhuman primate, primate, etc.), the capacity of the individual's immune system to synthesise antibodies, the degree of protection desired, the formulation of the vaccine, the treating doctor's assessment of the medical situation, and other relevant factors. It is expected that the amount will fall in a relatively broad range that can be determined through routine trials. In embodiments wherein pharmaceutical compositions of the present disclosure comprise RNA, the RNA content will generally be expressed in terms of the amount of RNA per dose. A preferred dose has <120µg RNA Docket No.: 70280WO01 e.g. <100µg (e.g.15-120µg or 15-100 µg, such as 15µg, 25µg, 50µg, 75µg or 100µg, or about 15µg, 25µg, 50µg, 75µg or 100µg). A further preferred dose has 1-100µg RNA (e.g. 1-90µg, 1-80µg, 1- 70µg, 1-60µg, 1-55µg or 1-50µg), with further preferred specific doses of 3µg, 6µg, 12.5µg, 25µg or 50µg; in particular wherein said further preferred dose (or specific dose) is administered to a subject at least twice, separated by 1-3 months, e.g. about 2 months apart or 2 months apart. Pharmaceutical compositions of the present disclosure may further comprise an adjuvant (i.e. an agent that enhances an immune response in a non-specific manner). Pharmaceutical compositions of the present disclosure (preferably when comprising a lipid nanoparticle comprising a nucleic acid of the present disclosure, preferably RNA) may be lyophilised. In some embodiments, pharmaceutical compositions of the present disclosure comprise (i) a nucleic acid (preferably RNA) encoding an RSV-F protein of the present disclosure, and (ii) a further nucleic acid (preferably RNA) encoding at least one further protein. The nucleic acids of (i) and (ii) may be comprised within the same carrier (preferably lipid nanoparticle), or within separate carriers (preferably lipid nanoparticles). In preferred embodiments, the at least one further protein is an antigen; and as such may comprise, or may be, a viral, bacterial, fungal, parasitic, tumour, or allergenic (i.e. from, or derived from, an allergen) antigen. The at least one further protein will typically be a pathogen antigen. The at least one further protein will typically be an antigen that is a surface polypeptide e.g. a spike glycoprotein, a haemagglutinin, an adhesin or an envelope glycoprotein. In a particular embodiment, the at least one further protein is an antigen from, or derived from, a virus, in particular a virus causing respiratory disease, in particular a seasonal virus causing respiratory disease. In embodiments wherein the at least one further protein is an antigen from, or derived from, a virus, examples of such viruses include: Coronavirus, Orthomyxovirus, Pneumoviridae, Paramyxoviridae, Poxviridae, Picornavirus, Bunyavirus, Heparnavirus, Filovirus, Togavirus, Flavivirus, Pestivirus, Hepadnavirus, Rhabdovirus, Caliciviridae, Retrovirus, Reovirus, Parvovirus, Herpesvirus, Papovaviruses and Adenovirus. In a preferred embodiment, the at least one further protein encoded by the nucleic acid of (ii) is a further Pneumoviridae protein (in particular a Pneumoviridae antigen). Useful further Pneumoviridae proteins (in particular, antigens) can be from an Orthopneumovirus or Metapneumovirus, in particular human RSV or human Metapneumovirus (hMPV). Useful further hMPV antigens include e.g. the F, N, P, M, M2-1, and M2 antigens (in particular, the F antigen). Such hMPV proteins (in particular, antigens) may be from, or derived from, the A or B subtype. In a preferred embodiment, the nucleic acid of (i) is RNA encoding an RSV-F protein of the present disclosure and the nucleic acid of (ii) is RNA encoding an hMPV antigen (in particular, the F antigen). In such RNA embodiments, a preferred patient group (in which the pharmaceutical composition may be used in therapy, in particular vaccination) is infants (see section entitled Medical uses and methods of treatment, below). Useful further human RSV antigens encoded by the nucleic acid of (ii) include e.g. the G, M1, M2-1, M2-2, Docket No.: 70280WO01 P, L, N, NS1, NS2 and SH antigens, in addition to further RSV-F antigens, i.e. of distinct amino acid sequence to the RSV-F protein of the present disclosure encoded by the nucleic acid. Such further human RSV proteins (in particular, antigens, in particular F antigens) may be from, or derived from, the A or B subtype, in particular the B subtype. In a preferred embodiment, the at least one further protein encoded by the nucleic acid of (ii) is a Coronavirus antigen. Useful Coronavirus antigens can be from a SARS coronavirus, in particular SARS-CoV2. Useful Coronavirus antigens (preferably SARS-CoV2 antigens) include the spike, M, E, HE, Nuclocapsid, Plpro and 3CLPro proteins, in particular spike protein. Preferably, the Coronavirus antigen is a SARS-CoV2 spike protein. Said SARS-CoV2 spike protein may be from any variant, e.g. Omicron (such as Omicron BA.1, BA.2, BA3, BA.4 or BA.5), Alpha, Epsilon, Eta, Theta, Kappa, Iota, Zeta, Mu, Lambda, Beta, Gamma, or Delta. Preferably, said SARS-CoV2 spike protein includes one or more mutations relative to the wild-type protein, in particular one or more (e.g. two) mutations to proline resides. Said one or more mutations may be introduced to stabilise said SARS- CoV2 spike protein in its pre-fusion conformation. In a preferred embodiment, the nucleic acid of (i) is RNA encoding an RSV-F protein of the present disclosure and the nucleic acid of (ii) is RNA encoding a Coronavirus antigen, e.g. as detailed above. In such RNA embodiments, a preferred patient group (in which the pharmaceutical composition may be used in therapy, in particular vaccination) is older adults (see section entitled Medical uses and methods of treatment, below). In another preferred embodiment, the at least one further protein encoded by the nucleic acid of (ii) is an Orthomyxovirus antigen. Useful Orthomyxovirus antigens can be from an influenza A, B or C virus. Useful Orthomyxovirus antigens (in particular influenza A, B or C virus antigens) include the haemagglutinin, neuraminidase and matrix M2 proteins, in particular haemagglutinin. Preferably, the Orthomyxovirus antigen is an influenza A virus haemagglutinin. Said influenza A virus hemagglutinin may be from any subtype e.g. H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15 or H16. In a preferred embodiment, the nucleic acid of (i) is RNA encoding an RSV-F protein of the present disclosure and the nucleic acid of (ii) is RNA encoding an Orthomyxovirus antigen, e.g. as detailed above. In such RNA embodiments, a preferred patient group (in which the pharmaceutical composition may be used in therapy, in particular vaccination) is older adults (see section entitled Medical uses and methods of treatment, below). In such RNA embodiments, the nucleic acid of (i) may encode an RSV-F protein of the present disclosure, the nucleic acid of (ii) may encode an Orthomyxovirus antigen, e.g. as detailed above, and (iii) a third nucleic acid may be present in the pharmaceutical composition which may encode a Coronavirus antigen, e.g. as detailed above in the preceding paragraph. In a further independent aspect, the present disclosure also provides a delivery device (e.g. syringe, nebuliser, sprayer, inhaler, dermal patch, etc.) comprising a pharmaceutical composition of the present disclosure. This device can be used to administer the composition to a vertebrate subject. Docket No.: 70280WO01 In a further independent aspect, the present disclosure also provides a method of preparing a pharmaceutical composition, comprising formulating a nucleic acid (preferably RNA), RSV-F protein or carrier (preferably lipid nanoparticle) of the present disclosure with a pharmaceutically acceptable excipient, to produce said composition. In particular, said pharmaceutical composition has the features as detailed above throughout this section. In a further independent aspect, the present disclosure also provides a kit comprising a nucleic acid, RSV-F protein, carrier, pharmaceutical composition or delivery device of the present disclosure, and instructions for use. Medical uses and methods of treatment The present disclosure also provides, in a further independent aspect, a nucleic acid (preferably RNA), RSV-F protein, carrier (preferably lipid nanoparticle) or pharmaceutical composition of the present disclosure, for use in medicine. Said use will generally be in a method for raising an immune response in a subject. The present disclosure also provides, in a further independent aspect, the use of a nucleic acid (preferably RNA), RSV-F protein, carrier (preferably lipid nanoparticle) or pharmaceutical composition of the present disclosure, in the manufacture of a medicament. Said medicament will generally be for raising an immune response in a subject. The present disclosure also provides, in a further independent aspect, a therapeutic method comprising the step of administering an effective amount of a nucleic acid (preferably RNA), RSV-F protein, carrier (preferably lipid nanoparticle) or pharmaceutical composition of the present disclosure to a subject (preferably a subject in need of such administration). Said method will generally be for raising an immune response in the subject. In another embodiment, the present disclosure provides a method of treatment of a subject comprising the step of administering an effective amount of the nucleic acid of the present disclosure to the subject. In one embodiment, the nucleic acid is RNA. In another embodiment, the present disclosure provides a method of treatment of a subject comprising the step of administering an effective amount of the RSV-F protein of the present disclosure. In another embodiment, the present disclosure disclosed a method of treatment of a subject comprising administering to the subject an effective amount of the pharmaceutical composition of the present disclosure. In one embodiment, the pharmaceutical composition comprises an adjuvant. The immune response is preferably protective and, preferably involves antibodies and/or cell-mediated immunity. Generally, the subject is a vertebrate, preferably a mammal, more preferably a human or large veterinary mammal (e.g. horses, cattle, deer, goats, pigs), even more preferably a human. The nucleic acids, RSV-F proteins, carriers, or pharmaceutical compositions of the present disclosure may be for use in the prevention, reduction or treatment of infection or disease. In addition, or alternatively, the nucleic acids, RSV-F proteins, carriers, or pharmaceutical compositions of the Docket No.: 70280WO01 present disclosure may be for use in the prevention, reduction or treatment of symptoms associated with infection or disease. The infection is generally one by, and said disease is generally one associated with, a Pneumoviridae virus. In preferred embodiments, the Pneumoviridae virus is an Orthopneumovirus, which is more preferably RSV, and even more preferable human RSV (including both the A and B subtypes thereof). Accordingly, the present disclosure also provides a nucleic acid, RSV-F protein, carrier or pharmaceutical composition of the present disclosure; for use in treating or preventing RSV (preferably a method of vaccination against RSV). The present disclosure also provides the use of a nucleic acid, RSV-F protein, carrier or pharmaceutical composition of the present disclosure, in the manufacture of a medicament for treating or preventing RSV (preferably wherein the medicament is a vaccine). The present disclosure also provides a method of inducing an immune response against RSV in a subject (preferably a method of vaccinating a subject against RSV), comprising administering to the subject an immunologically effective amount of the nucleic acid, RSV-F protein, carrier or pharmaceutical composition of the present disclosure to the subject. Vaccination according to the present disclosure may either be prophylactic (i.e. to prevent infection) or therapeutic (i.e. to treat infection), but will typically be prophylactic. Such methods of vaccination may comprise administration of a single dose. Alternatively, such methods of vaccination may comprise a vaccination regimen (i.e. administration of multiple doses). Such regimens may involve the repeated administration of an immunologically identical protein antigen (in the form of, or delivered via, a nucleic acid, RSV-F protein, carrier, or pharmaceutical composition of the present disclosure), in particular in a prime-boost regimen. In a prime-boost regimen, the first administration (“prime”) may induce proliferation and maturation of B and/or T cell precursors specific to one or more immunogenic epitopes present on the delivered antigen (induction phase). The second (and in some cases subsequent) administration (“boost”), may further stimulate and potentially select an anamnestic response of cells elicited by the prior administration(s). The different administrations may be given by the same or different routes e.g. a parenteral prime and mucosal boost, a mucosal prime and parenteral boost, etc. The prime administration(s) and boost administration(s) will be temporally separated, e.g. by at least: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or more months. In some embodiments, two prime administrations may be administered 3-9 weeks apart (e.g.4-9, 5-9, 6-9, 7-9 or 7-8 weeks apart, or about two months apart), followed by one or more boost administrations 4-14 months after the second prime administration (e.g.5-13, 6-13, 7-13, 8-13, 9-13, 10-13 or 11-13 months, or about one year). In some embodiments, prime administration is to a naïve subject. In some embodiments, the protein antigen may be delivered in the prime and boost administrations as, or via, different formats. For example, the protein antigen may be delivered as a protein for the prime administration(s), and via a nucleic acid (in particular RNA, in particular via a carrier comprising RNA) for the boost administration(s), or vice versa. Alternatively, different nucleic acid formats may be used, e.g. the protein antigen may be delivered via RNA (in particular via a carrier comprising RNA) Docket No.: 70280WO01 for the prime administration(s), and a via a viral vector (e.g. an adenoviral vector) for the boost administration(s), or vice versa. The nucleic acids, RSV-F proteins, carriers, or pharmaceutical compositions of the present disclosure will generally be administered directly to the subject. Direct delivery may be accomplished by parenteral injection (e.g. subcutaneously, intraperitoneally, intravenously, intramuscularly, intradermally, or to the interstitial space of a tissue). Alternative delivery routes include rectal, oral (e.g. tablet, spray), buccal, sublingual, vaginal, topical, transdermal or transcutaneous, intranasal, ocular, aural, pulmonary or other mucosal administration. Preferably, the nucleic acids, RSV-F proteins, carriers, or pharmaceutical composition of the present disclosure will be administered intramuscularly or intradermally (in particular via a needle such as a hypodermic needle), more preferably intramuscularly. The nucleic acids, RSV-F proteins, lipid carriers, or pharmaceutical compositions of the present disclosure may be used to elicit systemic and/or mucosal immunity. The subject of a method of vaccination according to the present disclosure may be a child (preferably an infant) or adult (preferably an older adult or pregnant female). Immunocompromised individuals may also be the subject of such vaccination (whether children or adults). Infant vaccination In a preferred embodiment, the nucleic acids, RSV-F proteins, carriers, or pharmaceutical compositions of the present disclosure are administered to infants (preferably human infants), as the subject of vaccination. The immune systems of infants are immature (see, e.g. [26]), hence this population is susceptible to RSV infection and resulting disease. Infant vaccination may prevent lower respiratory tract infection (in particular, bronchiolitis and (broncho-)pneumonia). The infant may be 0-12 months old. The infant may be less than one year old, such as less than: 11, 10, 9, 8, 7, 6, 5, 4 or less than 3 months old. The infant may be ≥one month old, such as ≥: 2, 3, 4, 5 or ≥6 months old. Preferably the infant is 2-6 months old (i.e. within and including the ages of 2 and 6 months), more preferably 2-4 months old. In a preferred embodiment, the infant was born from a female to whom an RSV vaccine (such as a nucleic acid, RSV-F protein, carrier, or pharmaceutical composition of the present disclosure) was administered, preferably while pregnant with said infant. The combination of maternal and infant vaccination may advantageously provide passive transfer of maternal antibodies (i.e. via the placenta and/or breast milk) to, in addition to active immunity generated by, the infant. Older adult vaccination In another preferred embodiment, the nucleic acids, RSV-F proteins, carriers, or pharmaceutical compositions of the present disclosure are administered to older adults (preferably human older adults), as the subject of vaccination. Older adults may suffer from age-related immunosenescence (reviewed Docket No.: 70280WO01 in, e.g. [27]), hence this population is also susceptible to RSV infection and resulting disease. Older adult vaccination may prevent lower respiratory tract infection (in particular, pneumonia). The older adult may be ≥50 years old, such as ≥: 55, 60, 65, 70, 75, 80, 85, 90, 95 or ≥100 years old. Preferably, the older adult is ≥60 or ≥65 years old (such as 60-120 or 65-120 years old). Pregnant female vaccination In another preferred embodiment, the nucleic acids, RSV-F proteins, carriers, or pharmaceutical compositions of the present disclosure are administered to pregnant females (preferably pregnant human females), as the subject of vaccination. The primary object of maternal vaccination is to protect the infant from RSV infection when born, e.g. through passive transfer of antibodies via the placenta and/or breast milk. The pregnant female may be in her first, second or third trimester of pregnancy, preferably third trimester. The pregnant female may be ≥20 weeks pregnant, such as ≥: 22, 24, 26, 28, 30, 32, 34, 36 or ≥38 weeks pregnant. Preferably, the pregnant female is ≥28 , ≥29 or ≥30 weeks pregnant (such as 28-43, 29-43 or 30-43 weeks pregnant). Preparing RSV-F proteins RSV-F proteins of the present disclosure can be prepared by routine methods, such as by expression in a recombinant host system using a nucleic acid expression vector (e.g. an expression vector as detailed in the section entitled Nucleic acid formats, above). Suitable recombinant host cells include, for example, insect cells (e.g. Sf9 cells, Sf21 cells, Tn5 cells, Schneider S2 cells, and High Five cells); mammalian cells (e.g. Chinese hamster ovary (CHO) cells, human embryonic kidney cells (e.g. HEK293, in particular Expi 293 cells), NIH-3T3 cells, 293-T cells, Vero cells, and HeLa cells); avian cells (e.g. chicken embryonic fibroblasts and chicken embryonic germ cells); bacteria; and yeast cells. HEK293 cells are preferred, more preferably Expi 293 cells (as were used in the examples). Accordingly, the present disclosure also provides, in one independent aspect, a host cell (in particular, those detailed above) comprising a nucleic acid of the present disclosure (in particular, an expression vector as detailed above) encoding an RSV-F protein of the present disclosure. The present disclosure also provides, in a further independent aspect, a host cell (in particular, those detailed above) comprising and/or expressing an RSV-F protein of the present disclosure. The present disclosure also provides, in a further independent aspect, a composition comprising a host cell (in particular, those detailed above) and (i) a nucleic acid of the present disclosure (in particular, an expression vector as detailed above) encoding an RSV-F protein of the present disclosure, and/or (ii) an RSV-F protein of the present disclosure. The present disclosure also provides, in a further independent aspect, an in vitro method for the production of an RSV-F protein of the present disclosure, comprising expressing a nucleic acid of the present disclosure (in particular, an expression vector as detailed above) encoding the RSV-F protein in a host cell (in particular, those detailed above). In an embodiment, the RSV-F protein is then purified. Docket No.: 70280WO01 RSV-F proteins of the present disclosure can be purified, following expression from a host cell, by routine methods, such as precipitation and chromatographic methods (e.g. hydrophobic interaction, ion exchange, affinity, chelating or size exclusion chromatography). The RSV-F proteins of the present disclosure can include a tag that facilitates purification, such as an epitope tag or a histidine (HIS) tag, to facilitate purification e.g. by affinity chromatography. General The practice of the present disclosure will employ, unless otherwise indicated, conventional methods of chemistry, biochemistry, molecular biology, immunology and pharmacology. The singular terms "a," "an," and "the" include plural referents unless context clearly indicates otherwise. Similarly, the word "or" is intended to include "and" unless the context clearly indicates otherwise. The term "plurality" refers to two or more. The term “at least one” refers to one or more. Unless specified otherwise, where a numerical range is provided, it is inclusive, i.e., the endpoints are included. The terms “at least”, “no more than” and other such terms preceding a list of values are applicable to all members of said list (not merely the first member thereof), unless otherwise stated. The term “comprising” encompasses “including” as well as “consisting” e.g. a composition “comprising” X may consist exclusively of X or may include something additional e.g. X + Y. The term “about” in relation to a numerical value x is optional and means, for example, x+10%. The word “substantially” does not exclude “completely” e.g. a composition which is “substantially free” from Y may be completely free from Y. Where necessary, the word “substantially” may be omitted from the definition of the present disclosure. References to charge, to cations, to anions, etc., are taken at pH 7. Embodiments The present disclosure also provides the following numbered embodiments. Combinations of features of the present disclosure presented below are exemplary, and not to be construed as exhaustive. 1. A recombinant nucleic acid encoding an RSV-F protein comprising a cytoplasmic tail; wherein the cytoplasmic tail is 5-23 residues in length. 2. The nucleic acid of embodiment 1, wherein the cytoplasmic tail is 5-8, such as 5-7, 5-6 or 4-5 residues in length. 3. The nucleic acid of embodiment 2, wherein the cytoplasmic tail is 5 residues in length. Docket No.: 70280WO01 4. The nucleic acid of claim 1, wherein the cytoplasmic tail is 8-12, such as 9-12, 10-12, 9-11, 9- 10, 10-11 or 10 residues in length. 5. The nucleic acid of embodiment 1, wherein the cytoplasmic tail is 10-18, such as 11-17, 12- 16, 13-16, 14-15 or 15 residues in length. 6. The nucleic acid of embodiment 1, wherein the cytoplasmic tail is 18-23, 19-23, 20-23, 21-23, 21-22, 22-23 or 22 residues in length. 7. The nucleic acid of any of embodiments 1-6, wherein cell-surface expression, optionally in human fibroblasts, optionally in human foreskin fibroblasts, optionally in human primary BJ cells, optionally the ATCC CRL-2522 cell line, of the RSV-F protein in trimeric, pre-fusion form from the nucleic acid is increased, relative to expression in such form of an RSV-F protein having the same amino acid sequence but comprising a wild-type cytoplasmic tail, such as according to SEQ ID NO: 3 or 4. 8. The nucleic acid of embodiment 7, wherein the increased cell surface expression is for a period of at least 24, 48, 72 or 96 hours. 9. A recombinant nucleic acid encoding an RSV-F protein comprising a cytoplasmic tail; wherein, relative to a cytoplasmic tail according to SEQ ID NO: 3 or 4, 2-20 residues are deleted from the cytoplasmic tail of the RSV-F protein. 10. The nucleic acid of embodiment 9, wherein 3-20 residues are deleted. 11. The nucleic acid of embodiment 9 or 10, wherein the residues are deleted from the C-terminal end of the cytoplasmic tail of the RSV-F protein. 12. The nucleic acid of embodiment 11, wherein 2-5, such as 2-4, 2-3, 3-4 or 3 residues are deleted from the C-terminal end of the cytoplasmic tail of the RSV-F protein. 13. The nucleic acid of any of embodiments 1 or 6-12, wherein the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-31 of SEQ ID NO: 69, or (ii) an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% identical to said positions and optionally the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). 14. The nucleic acid of any of embodiments 1 or 6-12, wherein the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-29 of SEQ ID NO: 70, or (ii) an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% identical to said positions and optionally the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). Docket No.: 70280WO01 15. The nucleic acid of embodiment 11, wherein 6-13, such as 7-13, 8-12, 9-11, 9-10, 10-11 or 10 residues are deleted from the C-terminal end of the cytoplasmic tail of the RSV-F protein. 16. The nucleic acid of any of embodiments 1, 5, 7-11 or 15 wherein the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-24 of SEQ ID NO: 71, or (ii) an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% identical to said positions and optionally the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). 17. The nucleic acid of embodiment 11, wherein 14-16, such as 14-15 or 15-16, or 15 residues are deleted from the C-terminal end of the cytoplasmic tail of the RSV-F protein. 18. The nucleic acid of any of embodiments 1, 4, 7-11 or 17, wherein the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-19 of SEQ ID NO: 72, or (ii) an amino acid sequence at least 60%, 70%, 80% or 90% identical to said positions and optionally the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). 19. The nucleic acid of embodiment 11, wherein 16-20, such as 17-20, 18-20 or 19-20 residues are deleted from the C-terminal end of the cytoplasmic tail of the RSV-F protein. 20. The nucleic acid of embodiment 19, wherein 20 residues are deleted from the C-terminal end of the cytoplasmic tail of the RSV-F protein. 21. The nucleic acid of any of embodiments 1, 2, 3, 7-11, 19 or 20, wherein the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-14 of SEQ ID NO: 73, or (ii) an amino acid sequence at least 60% or 80% identical to said positions and optionally the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). 22. The nucleic acid of any of embodiments 11-21, wherein the deletions increase the cell-surface expression, optionally in human fibroblasts, optionally in human foreskin fibroblasts, optionally in human primary BJ cells, optionally the ATCC CRL-2522 cell line, of the RSV-F protein in trimeric, pre-fusion form from the nucleic acid, relative to expression in such form of an RSV-F protein having the same amino acid but absent such deletions, such as an RSV-F protein comprising a cytoplasmic tail according to SEQ ID NO: 3 or 4. 23. The nucleic acid of embodiment 22, wherein the increased cell surface expression is for a period of at least 24, 48, 72 or 96 hours. 24. The nucleic acid of any preceding embodiment, wherein the cytoplasmic tail of the RSV-F protein comprises at least 5 residues that are C-terminal to position 549 of the RSV-F protein. Docket No.: 70280WO01 25. The nucleic acid of any preceding embodiment, wherein the RSV-F protein comprises an ectodomain comprising an F2 and an F1 domain, and a substitution relative to a wild-type RSV-F ectodomain, such as positions 26-109 and 137-523 of SEQ ID NO: 1 or 2, of a residue for a C residue in both of the F2 and F1 domains, introducing a disulphide bond between said C residues when the RSV-F protein is expressed. 26. The nucleic acid of embodiment 25, wherein the RSV-F protein comprises an ectodomain comprising substitutions as defined in preferred class (1). 27. The nucleic acid of embodiment 25 or 26, wherein the ectodomain comprises the substitutions 103C, 148C, 190I, and 486S. 28. The nucleic acid of any of embodiments 1-24, wherein the RSV-F protein comprises an ectodomain which comprises the substitution of at least two residues relative to a wild-type RSV-F ectodomain, such as positions 26-109 and 137-523 of SEQ ID NO: 1 or 2, at position 67 and/or 215. 29. The nucleic acid of embodiment 28, wherein the RSV-F protein comprises an ectodomain comprising substitutions as defined in preferred class (2). 30. The nucleic of embodiment 28 or 29, wherein the ectodomain comprises the substitutions 67I and 215P. 31. The nucleic acid of embodiment 28 or 29, wherein the ectodomain comprises the substitutions 66E, 67I, 76V, 215P and 486N. 32. The nucleic acid of any of embodiments 1-24, wherein the RSV-F protein comprises an ectodomain which comprises the substitution of at least two residues relative to a wild-type RSV-F ectodomain, such as positions 26-109 and 137-523 of SEQ ID NO: 1 or 2, for C residues, introducing a disulphide bond between said C residues when the RSV-F protein is expressed. 33. The nucleic acid of embodiment 32, wherein the RSV-F protein comprises an ectodomain comprising substitutions as defined in preferred class (3). 34. The nucleic acid of embodiment 32 or 33, wherein the ectodomain comprises the substitutions 149C, 155C, 190F, 207L, 290C and 458C; optionally with a linker joining the F2 and F1 domains, optionally replacing positions 104-144, optionally wherein the linker comprises or consists of an amino acid sequence according to SEQ ID NO: 13. 35. The nucleic acid of embodiment 34, wherein the ectodomain comprises the substitutions 102A, 149C, 155C, 190F, 207L, 290C, 373R, 379V, 447V and 458C; optionally with a linker joining Docket No.: 70280WO01 the F2 and F1 domains, optionally replacing positions 104-144, optionally wherein the linker comprises or consists of an amino acid sequence according to SEQ ID NO: 13. 36. The nucleic acid of embodiment 31 or 32, wherein ectodomain comprises the substitutions 155C, 190F, 207L and 290C. 37. The nucleic acid of any of embodiments 1-24, wherein the RSV-F protein comprises an ectodomain with substitutions as defined in preferred class (4). 38. The nucleic acid of embodiment 1-24 or 37, comprising (a): substitution at position 55 for T, C, V, I; optionally T, C or V; optionally T or V; optionally T; (b): substitution at position 215 for A, P, V, I, or F; optionally A, V, I, or F; optionally A or P; optionally A; and/or, optionally and, (c): substitution at position 228 for K, R, N, W, D, E, Q, H, S, T or Y; optionally K, R, W, N, Q, H, S, T or Y; optionally K, R, Q and N; optionally K, R or Q; optionally K or R, optionally K. 39. The nucleic acid of embodiment 1-24, 37 or 38, comprising the substitutions: (i) 55T, 152R, 215A, 228K, 315I, 346Q, 445D, 455V, 459M, 486C and 490C; (ii) 55T, 152R, 211N, 215A, 228K, 315I, 346Q, 348N, 445D, 455V, 459M, 486C and 490C; (iii) 55T, 152R, 215A, 228K, 315I, 346Q, 445D, 455V and 459M; (iv) 55T, 152R, 211N, 215A, 228K, 315I, 346Q, 348N, 445D, 455V and 459M; (v) 55T, 152R, 210H, 211N, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 445D, 455V and 459M; (vi) 55T, 215A, 228K, 241N, 315I, 348N, 455V and 459M; (vii) 55T, 215A, 228K, 315I, 348N, 455V and 459M; (viii) 55T, 215A, 228K, 315I, 348N, 455V and 459M; (ix) 55T, 152R, 210H, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 445D, 455V and 459M; (x) 55T, 152R, 210H, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 455V and 459M; (xi) 55T, 152R, 211N, 215A, 228K, 315I, 346Q, 348N, 455V and 459M; (xii) 55T, 152R, 215A, 228K, 315I, 346Q, 348N, 445D, 455V and 459M; or (xiii) 55T, 152R, 215A, 228K, 315I, 346Q, 348N, 455V and 459M. 40. The RNA of any preceding embodiment, wherein, when expressed, the RSV-F protein is in the pre-fusion conformation. Docket No.: 70280WO01 41. The nucleic acid of any preceding embodiment, wherein the RSV-F protein comprises an amino acid sequence having at least 70%, 75%, 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to positions 1-549 of SEQ ID NO: 1. 42. The nucleic acid of any preceding embodiment, wherein the RSV-F protein comprises an F2 domain comprising or consisting of an amino acid sequence having at least 70%, 75%, 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to positions 1-109 of SEQ ID NO: 1; and an F1 domain comprising or consisting of an amino acid sequence having at least 70%, 75%, 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99.5%, sequence identity to positions 137-523 of SEQ ID NO: 1. 43. The nucleic acid of any preceding embodiment, wherein the RSV-F protein comprises an F2 domain comprising or consisting of an amino acid sequence having at least 70%, 75%, 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to positions 26-109 of SEQ ID NO: 1; and an F1 domain comprising or consisting of an amino acid sequence having at least 70%, 75%, 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99.5%, sequence identity to positions 137-523 of SEQ ID NO: 1. 44. The nucleic acid of any preceding embodiment, wherein the RSV-F protein is of the A subtype. 45. The nucleic acid of any of embodiments 1-40, wherein the RSV-F protein comprises an amino acid sequence having at least 70%, 75%, 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to positions 1-549 of SEQ ID NO: 2. 46. The nucleic acid of any of embodiments 1-40 or 45, wherein the RSV-F protein comprises an F2 domain comprising or consisting of an amino acid sequence having at least 70%, 75%, 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to positions 1-109 of SEQ ID NO: 2; and an F1 domain comprising or consisting of an amino acid sequence having at least 70%, 75%, 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99.5%, sequence identity to positions 137-523 of SEQ ID NO: 2. 47. The nucleic acid of any of embodiments 1-40, 45 or 46, wherein the RSV-F protein comprises an F2 domain comprising or consisting of an amino acid sequence having at least 70%, 75%, 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to positions 26-109 of SEQ ID NO: 2; and an F1 domain comprising or consisting of an amino acid sequence having at least 70%, 75%, 80%, Docket No.: 70280WO01 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 99.5%, sequence identity to positions 137-523 of SEQ ID NO: 2. 48. The nucleic acid of any of embodiments 1-40 or 45-47, wherein the RSV-F protein is of the B subtype. 49. The nucleic acid of any preceding embodiment, wherein the nucleic acid is able to elicit a pre- fusion RSV-F-specific antibody response in vivo. 50. The nucleic acid of embodiment 49, wherein the antibody response is an IgG response. 51. The nucleic acid of any preceding embodiment, wherein the nucleic acid is able to elicit a neutralising antibody response against RSV in vivo 52. The nucleic acid of embodiment 51, wherein the RSV is of the A subtype. 53. The RSV-F protein encoded by the nucleic acid of any preceding embodiment. 54. The RSV-F protein of embodiment 53, in the form of a homotrimer. 55. The nucleic acid of any of embodiments 1-52, wherein the nucleic acid is RNA or DNA. 56. The nucleic acid of embodiment 55, wherein the nucleic acid is, or is comprised within, a viral vector; optionally wherein the viral vector is an adenovirus vector. 57. The nucleic acid of embodiment 55, wherein the nucleic acid is DNA; optionally wherein the DNA is a DNA plasmid. 58. The nucleic acid of embodiment 55, wherein the nucleic acid is RNA. 59. The RNA of embodiment 58, which is non-self-replicating RNA. 60. The RNA of embodiment 58, which is self-replicating RNA. 61. The RNA of any of embodiments 58-60, comprising, in the 5’ to 3’ direction: a 5’ Cap, a 5’ UTR, an open reading frame encoding the RSV-F protein, a 3’UTR, and a 3’ poly-A tail. 62. The RNA of embodiment 61, wherein the 5’ cap comprises a 7-methylguanosine linked 5’-to- 5’ to the 5’ first ribonucleoside by a triphosphate bridge, and wherein the first 5’ ribonucleoside comprises a 2’-methylated ribose (2’-O-Me). 63. The RNA of embodiment 61 or 62, wherein the 3’ poly-A tail comprises a contiguous stretch of 100-500 A ribonucleotides. 64. The RNA of embodiment 61 or 62, wherein the 3’ poly-A tail comprises at least two non- contiguous stretches of A ribonucleotides; optionally: (a) 25-35 and 65-90 ribonucleotides in Docket No.: 70280WO01 length respectively which are optionally orientated in the 5’ to 3’ direction, or (b) 25-35 and 25-45 ribonucleotides in length respectively which are optionally orientated in the 5’ to 3’ direction. 65. The RNA of any of embodiments 58-64, comprising a modified ribonucleotide. 66. The RNA of embodiment 65, wherein the modified ribonucleotide is 1mΨ 67. The RNA of embodiment 66, wherein the RNA comprises 1mΨ and neither standard U ribonucleotides nor other modified U ribonucleotides; optionally wherein the RNA comprises 1mΨ and neither standard U ribonucleotides nor other modified ribonucleotides. 68. The RNA of any of embodiments 58-67, having a GC content of 30-70%, 40-70%, 45-70%, 50-70%, or 55-70%. 69. The RNA of any of embodiments 58-67, having a GC content of 30-70%, 40-60%, 45-55%, 46-53%, 47-51%, or 48-50%. 70. A carrier comprising nucleic acid of any of embodiments 1-52 or 58-69. 71. The carrier of embodiment 70, which is a lipid nanoparticle. 72. The lipid nanoparticle of embodiment 71, comprising a mixture of cationic lipids, neutral lipids, sterols and polymer-conjugated lipids. 73. The lipid nanoparticle of embodiment 72, wherein the cationic lipid has a pKa of 5.0-8.0; optionally 5.0-7.6. 74. The lipid nanoparticle of embodiment 72 or 73, wherein the cationic lipid comprises a tertiary amine group. 75. The lipid nanoparticle of any of embodiments 72-74, wherein the polymer-conjugated lipid is a PEGylated lipid; optionally wherein the PEG has a weight average molecular weight of 1-3 kDa. 76. The lipid nanoparticle of any of embodiments 72-75, wherein the sterol is cholesterol or a cholesterol-based lipid. 77. The lipid nanoparticle of any of embodiments 72-76 comprising (in mole %) 30-60% cationic lipid, 35-70% sterol, 0.8-4.0% polymer-conjugated lipid, and 0-15% neutral lipid; optionally 40-50% cationic lipid, 41-49% sterol, 1.0-3.0% polymer-conjugated lipid and 8.0-11.0% neutral lipid. Docket No.: 70280WO01 78. The lipid nanoparticle of any of embodiments 72-77, wherein the molar ratio of protonatable nitrogen atoms in the cationic lipid to phosphates in the RNA (“N:P ratio”) is 5.0-8.0, 5.5-7.0, 5.5-6.5 or 5.0-6.0. 79. A pharmaceutical composition comprising the nucleic acid of any of embodiments 1-52 or 55- 57, RSV-F protein of embodiment 53 or 54, RNA of any of embodiments 58-69 or carrier of any of embodiments 70-78; optionally comprising a pharmaceutically acceptable excipient; optionally further comprising an adjuvant. 80. A vaccine composition comprising the nucleic acid of any of embodiments 1-52, 55 or 56, RSV-F protein of embodiment 53 or 54, RNA of any of embodiments 58-69, or carrier of any of embodiments 70-78; optionally comprising a pharmaceutically acceptable excipient; optionally further comprising an adjuvant. 81. The composition of embodiment 79 or 80, for use in medicine. 82. The composition for use of embodiment 81, for use in a method of raising an immune response in a subject; optionally a protective immune response in a subject. 83. The composition for use of embodiment 82, for use in the treatment or prevention of RSV. 84. The composition for use of embodiment 83, for use in a method of vaccinating a subject against RSV; optionally wherein the vaccination is prophylactic. 85. The composition for use of any of embodiments 82-84, wherein the subject is a human infant; optionally 2-6 months old. 86. The composition for use of any of embodiments 82-84, wherein the subject is a human older adult; optionally ≥50 years old, optionally ≥60 years old. 87. The composition for use of any of embodiments 82-84, wherein the subject is a pregnant human female; optionally ≥28 weeks pregnant. 88. A method of inducing an immune response against RSV in a subject, comprising administering to the subject an immunologically effective amount of the nucleic acid of any of embodiments 1-52 or 55-57, RSV-F protein of embodiment 53 or 54, RNA of any of embodiments 58-69, or carrier of any of embodiments 70-78. 89. A method of enhancing the cell surface expression of RSV-F antigen in a subject, comprising administering to the subject an immunologically effective amount of the nucleic acid of any of embodiments 1-52 or 55-57, RSV-F protein of embodiment 53 or 54, RNA of any of embodiments 58-69, or carrier of any of embodiments 70-78. Docket No.: 70280WO01 90. Use of the nucleic acid of any of embodiments 1-52 or 55-57, RSV-F protein of embodiment 53 or 54, RNA of any of embodiments 58-69, or carrier of any of embodiments 70-78, in the manufacture of a medicament. 91. Use according to embodiment 90, wherein the medicament is for treating or preventing RSV. 92. Use according to embodiment 91, wherein the medicament is a vaccine; optionally a prophylactic vaccine. 93. A kit comprising the nucleic acid of any of embodiments 1-52 or 55-57, RSV-F protein of embodiment 53 or 54, RNA of any of embodiments 58--69, or carrier of any of embodiments 70-78, and instructions for use. EXAMPLES Many modifications and variations of the present disclosure are possible in light of the above teachings. It is therefore to be understood that, within the scope of the appended claims, a skilled person in the art would recognise that the invention may be practiced otherwise than as specifically described. The illustrative embodiments and examples should not be construed as limiting the invention. Materials & Methods Cloning and expression of RSV-F monoclonal antibodies (Example 1-5, 8, 11 and 12) Plasmids encoding RSV-F antibodies, AM14, D25 and Motavizumab were transiently transfected in Expi293F cells (THERMO FISHER SCIENTIFIC) according to manufacturer’s instructions and media was harvested 6-7 days post transfection. The cell harvest media was passed over a MABSELECT SURE COLUMN (CYTIVA) and eluted with 0.1 M citrate pH 3 into 1 M Tris pH 9; buffer exchanged into 20 mM HEPES pH 7, 150 mM NaCl; followed by a final size exclusion chromatography step on a HILOAD 16/600 Superdex 30 pg column (CYTIVA) in 20 mM Hepes pH 7, 150 mM NaCl. Cloning of specific RSV-F mutants from mRNA (Example 1-5, 8, 11 and 12) RSV F wildtype (SEQ ID NO: 1) protein sequence was back-translated to a nucleic acid sequence using specific metrics for codon optimality. The DNA gBLOCKS (INTEGRATED DNA TECHNOLOGIES) were amplified by PCR, and ligation into a vector with a polyA tail. Amino acid substitutions N67I and S215P (also known as design F(ii)) were incorporated DNA constructs and encoded in the eventual mRNA and protein. The additional variations (also known as DS-Cav1, F(iii), F(i), F318 and F319) and their amino acid substitutions are shown in the Table 1. Table 1 – substitutions in parent mRNAs designs tested in cell-based assay Docket No.: 70280WO01 Design Substitutions relative to wild-type mRNA construct designation protein sequence (SEQ ID NO: 1) DS-Cav1 S115C, S190F, V207L, S290C KM03 (SEQ ID NO: 67); XW02 (SEQ ID NO: 76) used in Example 4 only F(ii) N67I, S215P KM135 (SEQ ID NO: 60) F(i) T103C, I148C, S190I, D486S KM173 (SEQ ID NO: 56) F(iii) (control), ^104-144; A149C, S155C, S190F, KM126 (SEQ ID NO: 75) which has full CT V207L, S290C, L373R, Y458C; deletion ^ ^ ^ ^-574* F318 S55T, V152R, S215A, N228K, K315I, KM119 (SEQ ID NO: 48) A346Q, S348N, K445D, T455V, V459M; F319 S55T, V152R, Q210H, S215A, KM120 (SEQ ID NO: 52) N228K, A241N, K315I, A346Q, S348N, K419D, T455V, V459M *F(iii) mutations made against a different background (wild-type) sequence to SEQ ID NO: 1 For CT truncating experiments, the CT was selectively removed in part or in whole from these constructs to create deletion (ΔCT) mutants. For this, NEB Q5 Site-Directed Mutagenesis Kit (NEB # E0554) was used to generate 7 CT deletion constructs: FL (“full length”, or “reference CT”), ΔCT3, ΔCT5, ΔCT10, ΔCT15, ΔCT20 and ΔCT25 Table 2 – C-terminal, cytoplasmic tail (CT) variations CT description CT AA sequence 1 Reference RSV F CT, including AA₅₄₁ LIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN additional transmembrane (TM) domain (SEQ ID NO: 68) residues N-terminal to CT start 2 _ΔCT3, including additional TM domain AA541 LIAVGLLLYCKARSTPVTLSKDQLSGINNIA (SEQ residues N-terminal to CT start ID NO: 69) 3 ΔCT5, including additional TM domain AA₅₄₁ LIAVGLLLYCKARSTPVTLSKDQLSGINN (SEQ ID residues N-terminal to CT start NO: 70) Docket No.: 70280WO01 4 _ΔCT10, including additional TM AA541 LIAVGLLLYCKARSTPVTLSKDQL (SEQ ID NO: domain residues N-terminal to CT start 71) 5 ΔCT15, including additional TM AA₅₄₁ LIAVGLLLYCKARSTPVTL (SEQ ID NO: 72) domain residues N-terminal to CT start 6 ΔCT20, including additional TM AA₅₄₁ LIAVGLLLYCKARS (SEQ ID NO: 73) domain residues N-terminal to CT start 7 ΔCT25 (TM domain residues only) AA₅₄₁ LIAVGLLLY (SEQ ID NO: 74) Briefly, the full-length constructs were combined with a forward primer combined with a unique reverse primer to create each ΔCT construct. The reverse primers were designed in which the 3’ end PCR annealing starting points are at 7 different positions: position d0, end of coding region; position d3, 3 amino acid residues upstream of the end of coding region; position ^5, 5 residues to the end; position ^10, 10 residues to the end; position ^15, 15 residues to the end; position ^20, 20 residues to the end; position ^25, 25 residues to the end, which is the entire CT region. The PCR reaction was heated to 98 °C for 30 seconds, followed by 16 cycles at 98 °C for 10 seconds, 69 °C for 30 seconds, 72 °C for 30 seconds. and a final extension of 72 °C for 2 min. The 7 PCR products were treated with KLD enzyme (NEB E0554) at room temperature for 5 minutes. Transformation with competent cells (NEB C3040H) was carried out by following manufacture instructions.24 hours after, colonies were screened to identify correct sequences. In the DNA sequences of CT deletion constructs, the T7 promotor region and the UTRs were appended to 5’ and 3’ of the coding regions (5’ and 3’ “UTR4”) and a polyA tail is after 3’ UTR region. The final plasmids were validated by Sanger sequencing and purified for mRNA production. In Example 8, the following mRNA constructs were tested: Table 5 – substitutions in mRNA-encoded protein designs tested in cell-based assay Designation mRNA construct Substitutions relative to wild-type RSV-F design in Figures designation 8-10 (x axis) and Ex 8 n/a All mRNAs encode RSV-F proteins n/a having these mutations relative to WT (SEQ ID NO: 1). Further mutations in each RSV-F design are listed below. Docket No.: 70280WO01 S55T, V152R, S215A, N228K, K315I, A346Q, K445D, T455V, V459M 1) KM112 (SEQ ID NO: S211N, S348N F217 (SEQ ID 78) NO: 129) 2) KM112d20 (SEQ ID S211N, S348N, Δ555-574 F217d20 (SEQ NO: 79) ID NO: 80) 3) KM211 (SEQ ID NO: S211N, S348N, D486C, A490C F528 (SEQ ID 81) NO: 82) 4) KM212 (SEQ ID NO: S211P, N216P, S348N, D486C, A490C R701 (SEQ ID 83) NO: 84) 5) KM213 (SEQ ID NO: S211N, S348N, D486C, A490C, 103- R702 (SEQ ID 85) 145SubsGS NO: 86) 6) KM214 (SEQ ID NO: S211N, S348N, D486C, A490C, 104- R703 (SEQ ID 85) 144SubsGS NO: 88) 7) KM215 (SEQ ID NO: S348N, D486C, A490C R704 (SEQ ID 89) NO: 90) 8) KM223 (SEQ ID NO: S211N, S348N, D486C, A490C, Δ555- F528d20 (SEQ 91) 574 ID NO: 92) 9) KM224 (SEQ ID NO: S211P, N216P, S348N, D486C, A490C, R701d20 (SEQ 93) Δ555-574 ID NO: 94) 10) KM225 (SEQ ID NO: S211N, S348N, D486C, A490C, Δ555- R702d20 (SEQ 95) 574, 103-145SubsGS ID NO: 96) 11) KM226 (SEQ ID NO: S211N, S348N, D486C, A490C, Δ555- R703d20 (SEQ 97) 574, 104-144SubsGS ID NO: 98) 12) KM227 (SEQ ID NO: S348N, D486C, A490C, Δ555-574 R704d20 (SEQ 99) ID NO: 100) 13) KM235 (SEQ ID NO: R712 (SEQ ID 101) NO: 102) Docket No.: 70280WO01 14) KM236 (SEQ ID NO: D486C, A490C R713 a.k.a 103) F647 (SEQ ID NO: 104) 15) KM237 (SEQ ID NO: S211P, N216P, D486C, A490C R714 (SEQ ID 105) NO: 106) 16) KM238 (SEQ ID NO: D486C, A490C, 103-145SubsGS R715 a.k.a. 107) F651 (SEQ ID NO: 108) 17) KM239 (SEQ ID NO: D486C, A490C, 104-144SubsGS R716 (SEQ ID 109) NO: 110) 18) KM240 (SEQ ID NO: S211P, N216P, D486C, A490C, 103- R717 (SEQ ID 111) 145SubsGS NO: 112) 19) KM241 (SEQ ID NO: S211P, N216P, D486C, A490C, 104- R718 (SEQ ID 113) 144SubsGS NO: 114) 20) KM242 (SEQ ID NO: Δ555-574 R712d20 (SEQ 115) ID NO: 116) 21) KM243 (SEQ ID NO: D486C, A490C, Δ555-574 R713d20 a.k.a 117) F647d20 (SEQ ID NO: 118) 22) KM244 (SEQ ID S211P, N216P, D486C, A490C, Δ555- R714d20 (SEQ NO: 119) 574 ID NO: 120) 23) KM245 (SEQ ID NO: D486C, A490C, Δ555-574, 103- R715d20 a.k.a. 121) 145SubsGS F651d20 (SEQ ID NO: 122) 24) KM246 (SEQ ID NO: D486C, A490C, Δ555-574, 104- R716d20 (SEQ 123) 144SubsGS ID NO: 124) 25) KM247 (SEQ ID NO: S211P, N216P, D486C, A490C, Δ555- R717d20 (SEQ 125) 574, 103-145SubsGS ID NO: 126) 26) KM248 (SEQ ID NO: S211P, N216P, D486C, A490C, Δ555- R718d20 (SEQ 127) 574, 104-144SubsGS ID NO: 128) Docket No.: 70280WO01 In Example 11, mRNA and protein construct details tested are set out in Table 8, below. In Example 12, CT lengths tested using design F(ii) are set out in Table 9, below. In vitro transcription to generate mRNA for RSV-F variations (Example 1-5, 8, 11 and 12) The plasmids were linearized with the BspQI restriction enzyme (NEW ENGLAND BIOLABS) to produce the DNA templates for in vitro transcription. mRNAs were produced by in vitro transcription with capping analogue (TRILINK CLEANCAP A/G) and 100% uridine replacement (with 1mΨ), followed with DNase I, phosphatase treatments (NEW ENGLAND BIOLABS) and silica column purification (QIAGEN). Newly synthesized mRNAs were validated by Tapestation (Agilent) and denaturing RNA gels. Cell culture conditions (Example 1-5, 8, 11 and 12) Primary BJ cells (ATCC, CRL-2522) were maintained by routine passaging in growth media (DMEM (LONZA 12-614F) supplemented with 10% FBS (CORNING 35-016-CV), antibiotic (GIBCO 15140- 122) and glutamine (GIBCO 25030-081)) and grown at 37°C, 5% CO₂. Forward transfection of candidate mRNAs (Example 1-5, 8, 11 and 12) BJ cells were seeded in growth media at 1.5x105 cells/mL onto 96-well, clear-bottom, black-walled imaging microwell plates (PERKIN ELMER 6055302). The following day, target mRNAs were complexed with TRANSIT mRNA transfection reagent (MIRUS mir2250) in OPTIMEM (GIBCO 31985-070). Each target mRNA was forward transfected into BJ cell monolayers using 0.35% transfection reagent (final concentration) with mRNAs diluted to 0.454ng/uL (final concentration), or water-only negative control. The transfected BJ cells were incubated according to the time-course assay. Indirect immunofluorescent labelling and detection of surface-expressed RSV F (Example 1-5, 8, 11 and 12) At the appropriate hours post-transfection (hpt), (1, 8, 24, 48, 72, 96 hpt), the cell media was removed from cells in 96-well format and cell monolayers were rinsed once with PBS with calcium and magnesium (THERMOFISHER 14080055). The cell monolayers were fixed in 4% paraformaldehyde (THERMOFISHERSCIENTIFIC J19943-K2) for 15min. Fixed cells were stored in PBS at 4C until cells can be immunolabeled as a batch. The fixed cell monolayers were rinsed twice with PBS (VWR 02-0119-1000). Nonspecific antibody- binding for fixed cells was blocked using 1% Normal Horse Serum (GIBCO 16050-130) in PBS (1%NHS-PBS). RSV F protein was labelled by incubating cell monolayers with the respective human anti-RSV F monoclonal antibodies: AM14, D25, motavizumab. Each well was incubated with 331ng of the respective antibody in blocking media overnight at 4C. Cell monolayers are rinsed 3 times with 1%NHS-PBS. Indirect immunofluorescent detection of RSV F expression was completed by incubating cell monolayers with goat anti-human antibody with ALEXA647 (THERMOFISHER A- 21445) diluted 1:2000 in 1%NHS-PBS. Additionally, cell nuclei were co-labelled with DYECYCLE Docket No.: 70280WO01 Violet (THERMOFISHER V35003) following manufacturer’s recommendations. Cell monolayers are rinsed 3 times with 1% NHS-PBS then cells are stored in PBS for imaging. 9 fields per well were imaged in the DYECYCLE Violet and Alexa647 fluorescent channels using the 10x objective on the THERMOSCIENTIFIC Cell Insight CX7 automated imaging system. Image analysis is completed using the Target Activation protocol associated with the CELLOMICS (HCS NAVIGATOR Ver 6.6.2 Build 8533) image analysis system. Data analysis was completed using MICROSOFT EXCEL and PRISM GRAPHPAD. In vivo RNA immunisation (Example 6) All recombinant RNA molecules were produced by in vitro transcription using N1-methyl pseudouridine to replace all uridines. All recombinant RNA molecules comprised a cap-1 5’ cap (TRILINK CLEANCAP) and a 3’ poly(A) tail. The mRNAs were purified and evaluated for mRNA integrity (by capillary and glyoxal denaturing gel electrophoresis). The RV39 LNP mRNA constructs were then formulated in LNPs comprising 40 mol% cationic lipid RV39; 2 mol% PEG-conjugated lipid; 48 mol% cholesterol; and 10 mol% 1,2-diastearoyl-sn-glycero- 3-phosphocholine (DSPC). Female BALB/c mice were 7 - 8 weeks old at day 0 of the study. An insulin syringe with a permanently attached needle was used to administer 50 µL (25 µL in each hindleg thigh muscle) of either saline or a high (2 µg) or low (0.2 µg) dose of F(iii) which includes a full cytoplasmic tail deletion (dCT), F(i), F(i) ΔCT20, F(ii), F(ii) ΔCT20 (low dose only ), DS-Cav1 (high dose only), F318, F318 ΔCT20, F319, or F319 ΔCT20 into each mouse on day 0 and day 21 (see Table 4 for mRNA construct designations). The groups of animals, formulation lot numbers, stock concentrations, number of vials, and storage temperatures were as follows (Table 3): Table 3 –in vivo RNA immunisation study design Immunoge Lot Stock Dose Number Number Storage n N Concentratio of vials of Temperature Group umber n supplied Animals (°C) As Supplied 1 Saline NA from NA NA 5 RT Manufacturer 2 vials for 2 2µg 2 ug dose 8 F(iii) 59 µg/mL (1.1 mL LNPs 32886a -80°C (RV39) material 3 0.2µg per vial) 8 Docket No.: 70280WO01 4 2µg 8 s 52 2 vials for F(i) LNP µg/mL (RV39) 32886b 0.2 ug ⁵ 0.2µg dose (0.3 8 mL material 6 per vial) F(i) 2µg ⁸ ΔCT20 66 µg/mL LNPs 32886c ⁷ (RV39) 0.2µg ⁸ 8 2µg ⁸ F(ii) LNPs 48 µg/mL (RV39) 32886d ⁹ 0.2µg ⁸ F(ii) 55 µg/mL 10 ΔCT20 LNPs 32886e 0.2µg ⁸ (RV39) 65 µg/mL DS-Cav1 11 LNPs 32886f 2µg ⁸ (RV39) 12 2µg ⁸ F318 49 µg/mL LNPs 32886g (RV39) ¹³ _0.2µg ⁸ 14 F318 2µg ⁸ ΔCT20 43 µg/mL LNPs 32886h ¹⁵ (RV39) _0.2µg ⁸ F319 52 µg/mL 16 LNPs 32886i 2µg 8 (RV39) Docket No.: 70280WO01 1⁷ _0.2µg ⁸ 18 F319 2µg ⁸ ΔCT20 52 µg/mL LNPs 32886j 1⁹ (RV39) _0.2µg ⁸ Table 4 –in vivo RNA immunisation study – construct details RSV-F construct mRNA construct designation F(iii) KM126 (SEQ ID NO: 75) F(i) KM173 (SEQ ID NO: 56) F(i) ΔCT20 KM173d20 (SEQ ID NO: 58) F(ii) KM135 (SEQ ID NO: 60) F(ii) ΔCT20 KM140 (SEQ ID NO: 65) DS-Cav1 XW02 (SEQ ID NO: 76) F318 KM119 (SEQ ID NO: 48) F318 ΔCT20 KM119d20 (SEQ ID NO: 50) F319 KM120 (SEQ ID NO: 52) F319 ΔCT20 KM120d20 (SEQ ID NO: 54) On day 21, mice were anesthetized under isoflurane to collect 100 μL of whole blood (40 μL of serum) by submandibular collection method. On day 35, mice were anesthetized under isoflurane and terminally exsanguinated by cardiac stick to obtain an estimated 200 μL to 500 μL of whole blood, (100 μL of serum). RSV pre-F IgG binding antibody titres and RSV A neutralising antibody titres were measured on day 21 and day 35 using the following methods. Docket No.: 70280WO01 IgG Binding Assay: The LUMINEX assay was designed to measure the levels of RSV Pre-Fusion protein specific IgG binding antibodies from immunized mice. LUMINEX microspheres (MAGPLEX microspheres, LUMINEX CORP from Austin, TX) were coupled with RSV preF antigen using sulfo- NHS and EDC, according to manufacturer’s instructions. In a 96-well plate, 2,000 microspheres/well are added in a volume of 50 µl PBS with 1% BSA + 0.05% Na Azide (assay buffer) to 100 µl of mouse serum serial diluted. After incubation of the microspheres and serum on an orbital shaker, covered, at RT for 60 minutes, the microspheres are washed 2 times with 200 µl/well of PBS, 0.05% Tween-20 (wash buffer) on a plate washer using a magnet to allow settling of beads between washes. Following the wash, 50 µL/well of r-Phycoerythrin (r-PE) conjugated anti-mouse IgG (JACKSON IMMUNORESEARCH) was added, and plates are incubated, covered, on an orbital shaker at RT for 60 minutes. After a final plate wash (same as described above), the samples were resuspended in PBS, covered, and incubated at RT on an orbital shaker for 20 minutes. Fluorescent intensity is measured using a LUMINEX FLEXMAP 3D. The raw data was analyzed using a SOFTMAX PRO template, where the serum sample binding potency was interpolated based on a four-parameter logistic fit of the standard curve. Serum anti-RSV preF IgG binding was calculated in terms of Assay Units (AU) using a reference standard assigned to a concentration of 100 AU. RSV A neutralising antibody titre assay: Heat-inactivated sera (incubated for 30 min at 56°C) were diluted 3-fold starting at 1/8 (for a final dilution of 1/16). A control serum (WYETH Human Reference Sera from WHO/NIBSC) was included at a starting dilution of 1/64 (1/128 final). For the serial dilutions, 30μL of diluted serum was added on top of 60μL of RSV media (BIORICH DMEM supplemented with 3%-fetal bovine serum (FBS; MOREGATE, FBSAE1000), 2 mM L-Glutamine, and 50 μg/mL Gentamicin). RSV lab-adapted A-Long virus was diluted to approximately 50-150 foci- forming units per 25μL. 60μL of virus was added into the wells with the same volume of serum dilutions and incubated for 2 hours at 35°C 5% CO2. After incubation, 50μL of the serum-virus mixture was added on top of the vero cells (seeded the day before the test at a density of 15000 cells/well, to reach a minimum of 80% confluency) and incubated for 2 hours at 35°C 5% CO2. After incubation, serum-virus supernatant was removed and 200μL of 0.5% carboxymethyl cellulose + RSV media was added on top of the cells. Plates were incubated for 2 days (max of 42 hours) at 35°C 5% CO₂. Plates were then washed 2 times with 100μL of PBS and 50μL of 1% paraformaldehyde was added per well. Plates were covered in aluminium and incubated overnight at 4°C. The next day, plates were rinsed 3 times with 150μL of PBS.100μL of blocking solution (2% milk + PBS) was added on top of the wells and incubated for 1 hour at 37°C. After incubation, plates were rinsed 3 times with 200μL of PBS. 50μL of primary goat anti-RSV polyclonal Ab (BIODESIGN, B65860G) diluted 1:400 in blocking solution was added per well and plates were incubated for 1 hour at 37°C.50μL of secondary Ab rabbit anti-goat HRP (AGRISERA, AS10659) diluted 1:1500 in blocking solution was added per well and plates were incubated for 1 hour at 37°C. After 1 hour, plates were rinsed 3 times with 200μL of PBS and 50μL of TRUEBLUE Peroxidase substrate (KPL, 5510-0049) was added on top. After an Docket No.: 70280WO01 incubation for 5-15 minutes, plaques were then washed extensively with DI water and let to dry. Imaging of the plaques was done using an AXIOVISION microscope. Effective dilution 60 (ED60) values, corresponding to the reciprocal serum dilution associated with 60% reduction in FFU counts, were determined using a linear model. Expression and Purification of RSV-F mutants, DS-Cav1 and RSV-F mAbs (Example 9) RSV-F mutants were synthesized (GENEWIZ/AZENTA) and cloned into a CMV-based vector with a C-terminal thrombin-cleavable double Strep tag II tag followed by a 6x His-tag. DS-Cav1 and RSV-F mutants were transiently expressed in Expi293 F cells (THERMO FISHER SCIENTIFIC). Media was harvested after 4 days, and purified using affinity chromatography, either nickel affinity or strep-tag affinity. Briefly, for nickel affinity chromatography, cell harvest medium was passed over a HisTrap Excel column (CYTIVA) and eluted with a step gradient of imidazole. For strep-tag affinity, the harvest medium was buffer exchanged into 50 mM Tris pH 8, 300 mM NaCl, passed over a StrepTrap HP column (CYTIVA) and eluted with elution buffer (100 mM Tris pH 8, 150 mM NaCl, 1 mM EDTA and 2.5 mM desthiobiotin). This was followed by a final size exclusion chromatography polishing step. The oligomeric state and protein integrity of DS-Cav1 and RSV-F mutants were confirmed by High Performance Liquid Chromatography (HPLC) on a WATERS ALLIANCE HPLC system. 20 µg of purified DS-Cav1 or RSV-F mutant were loaded onto a SUPEROSE 6 Increase 3.2/300 column (CYTIVA) and an isocratic gradient of a mobile phase composed of 20 mM Tris pH 7.5, 150 mM NaCl at a flow rate of 0.05 mL/min for a total run time of 60 min was used. RSV antibodies, AM14, D25, Motavizumab, and RSB1, were transiently transfected in EXPI93F cells (THERMO FISHER SCIENTIFIC) according to manufacturer’s instructions and media was harvested 6-7 days post transfection. The cell harvest media was passed over a MABSELECT SURE COLUMN (CYTIVA) and eluted with 0.1 M citrate pH 3 into 1 M Tris pH 9; buffer exchanged into 20 mM HEPES pH 7, 150 mM NaCl; followed by a final size exclusion chromatography step on a HILOAD 16/600 Superdex 30 pg column (CYTIVA) in 20 mM Hepes pH 7, 150 mM NaCl. Initial Quantitation and Antigenicity using Biolayer Interferometry (Example 9) Quantitation experiments were performed on the unpurified cell harvest media of 6x His-tagged DS- Cav1 and RSV-F mutants using the Octet Red 384 instrument (SARTORIUS). Purified DS-Cav1 diluted in EXPI293 expression media with 0.1% BSA, 0.05% Tween-20 was used to make a standard curve. BSA and Tween-20 were added to DS-Cav1 and RSV-F mutants unpurified cell harvest media to a final concentration of 0.1% and 0.05%, respectively.6x His-tagged purified DS-Cav1 and RSV-F mutant unpurified cell harvest media was captured on HIS2 biosensors for 2 min and the capture level was recorded. The concentrations were determined using unweighted 4 parameter logistics curve fitting in the manufacturer’s analysis software (Data Analysis HT 12.0.1.55). Docket No.: 70280WO01 Initial antigenicity experiment was performed on the unpurified cell harvest media of DS-Cav1 and RSV-F mutants to determine binding to AM14, D25, Motavizumab, and RSB1 mAbs using the OCTET Red 384 (SARTORIUS). mAbs were diluted to 10 µg/mL in 1xPBS with 0.1% BSA and 0.05% Tween-20. BSA and Tween-20 was added to DS-Cav1 and RSV-F mutant unpurified cell harvest media to a final concentration of 0.1% and 0.05%, respectively. AHC biosensors were regenerated in 10 mM Glycine pH 1.5 before and between experiments. AHC biosensors were washed in 1x PBS with 0.1% BSA and 0.05% Tween-20 for 30 sec, mAbs were loaded for 60 sec, and washed for 30 sec before capturing DS-Cav1 or RSV-F mutants from the unpurified cell harvest media. Binding and dissociation of DS-Cav1 and RSV-F mutants was measured for 180 sec each. The response of DS-Cav1 binding to each mAb was compared to the RSV-F mutants’ response to each mAb to determine yes or no binding. Expression in human skeletal muscle cells and dendritic cells (Example 10) Human skeletal muscle cells were maintained in media (RPMI1640, GIBCO) supplemented with IL4 (MILTENYI 130-093-922) and GM-CFS (MILTENYI 130-093-865) for 5 days. RPMI was supplemented with 10% FBS (CORNING 35-016-CV), antibiotic (GIBCO 15140-122) and glutamine (GIBCO 25030-081)) and grown at 37°C, 5% CO2. Monocyte-derived dendritic cells were maintained and differentiated in media (RPMI1640, GIBCO) supplemented with IL4 (MILTENYI 130-093-922) and GM-CFS (MILTENYI 130-093-865) for 5 days. RPMI was supplemented with 10% FBS (CORNING 35-016-CV), antibiotic (GIBCO 15140- 122) and glutamine (GIBCO 25030-081)) and grown at 37°C, 5% CO². RNA transfection and high content imaging was performed as per Examples 1-5, 8, 11 and 12 (using D25 antibody). In vivo RNA immunisation (Example 13) All mRNA molecules were produced and formulated into LNPs as per Example 6. Female BALB/c mice were 7 - 8 weeks old at day 0 of the study. An insulin syringe with a permanently attached needle was used to administer 50 µL (25 µL in each hindleg thigh muscle) of either saline or 0.5 µg dose of F528, F647, F647 ΔCT20, F651 ΔCT20, F(iii) which includes a full cytoplasmic tail deletion (dCT), F(i), F(ii), or DS-Cav1 into each mouse on day 0 and day 21. The groups of animals, formulation lot numbers, stock concentrations, number of vials, and storage temperatures were as follows: Table 10 – further in vivo RNA immunisation study design p Immunogen Lot Stoc Number Number Storage Grou k Dose Number Concentration of vials of Temperature supplied Animals (°C) Docket No.: 70280WO01 As Supplied ¹ Saline NA from NA NA 3 RT Manufacturer 2 F528 LNPs (RV39) 39371a 54 µg/mL 17 3 F647 LNPs (RV39) 39371b 51 µg/mL 17 4 F647 ΔCT20 LNPs (RV39) 39371c 53 µg/mL 17 5 F651 ΔCT20 LNPs (RV39) 39371d 58 µg/mL 2 vials 17 0.5µ (1.2 mL g material -80 6 F(iii) 39371f 57 µg per vial) LNPs (RV39) /mL 17 7 F(i) LNPs (RV39) 39371g 56 µg/mL 17 8 F(ii) LNPs (RV39) 39371h 53 µg/mL 17 9 DS-Cav1 LNPs (RV39) 39371i 57 µg/mL 17 Table 12 – further in vivo RNA immunisation study – construct details RSV-F construct mRNA construct designation F(iii) KM126 (SEQ ID NO: 75) F(i) KM173 (SEQ ID NO: 56) F(ii) KM135 (SEQ ID NO: 60) DS-Cav1 XW02 (SEQ ID NO: 76) F528 KM211 (SEQ ID NO: 81) Docket No.: 70280WO01 F647 KM236 (SEQ ID NO: 103) F647 ΔCT20 KM243 (SEQ ID NO: 117) F651 ΔCT20 KM245 (SEQ ID NO: 121) On day 21, mice were anesthetized under isoflurane to collect 100 μL of whole blood (40 μL of serum) by submandibular collection method. On day 35, mice were anesthetized under isoflurane and terminally exsanguinated by cardiac stick to obtain an estimated 200 μL to 500 μL of whole blood, (minimum 100 μL of serum). RSV pre-F and post-F IgG binding antibody titres and RSV A neutralising antibody titres were measured on day 21 and day 35 using the following method. RSV F IgG Binding: A multiplex assay was performed to evaluate titres of RSV pre-F- and post-F- specific antibodies in the serum of the mice immunized with new non replicating RSV mRNA vaccines. LUMINEX microspheres (MAGPLEX microspheres, LUMINEX from Austin, TX) were coupled with RSV post-F and pre-F antigen by chemical coupling according to manufacturer instructions. In 96 well plates, 2000 microspheres/ well were added in a volume of 50 µL 1X PBS with 1% BSA + 0.05% Na Azide (assay buffer) to five-fold serial dilutions of mouse serum down each column. After incubation of the microspheres and serum on an orbital shaker, covered, at RT for 60 minutes, the microspheres were washed two times with 200 µL/well of PBS with 0.05% Tween-20 (wash buffer) on a plate washer using a magnet to allow settling of beads between washes. Following the wash, 50 µL/well of r-Phycoerythrin (r-PE) conjugated anti-mouse IgG (JACKSON IMMUNORESEARCH) was added at a 1:50 dilution, and plates were incubated (covered) on an orbital shaker at room temperature (RT) for 60 minutes. After a final plate wash (same as described above) and incubation (covered, RT) with PBS on an orbital shaker for 20 minutes, fluorescent intensity was measured using a LUMINEX FLEXMAP 3D (LIFE TECHNOLOGIES model FM3D000). The raw data was analyzed using a SOFTMAX PRO template, where the serum sample binding potency was interpolated based on a five-parameter logistic fit of the standard curve. Serum anti-RSV F binding was calculated in terms of ASSAY Units (AU) using a reference standard assigned to a concentration of 100 AU. Neutralising antibody titres (against RSV A and B strains) were measured on day 21 and day 35 as per Example 6. Overview RSV-F protein (Table 1) is the primary target for a high quality vaccine to prevent severe illness and adverse outcomes from RSV infection.. Potential mRNA-based vaccine designs encode a glycoprotein that is processed, folded and exported to the cell surface, resulting in a trimeric RSV F protein with Docket No.: 70280WO01 three distinct domains: the extracellular domain, transmembrane domain and CT residing on the cytoplasmic face of the cell surface. Furthermore, select truncation of the RSV F CT was used to produce a mRNA vaccine design with further unique features, as discussed in detail below. Example 1 Human primary BJ cells are permissive for the cell-surface expression of RSV F protein encoded by exogenous mRNAs. The steady-state, total cell-surface RSV F protein expression of the design, F318 CT ^20, is observed to increase from 8 hours post transfection (Figure 1A”) to 24 hours post transfection (Figure 1B”) in BJ cells and decay in the subsequent 3 days (Figure 1, C”-E”). Quantification of RSV F levels using High Content imaging and image analysis in individual BJ cells in the transfected cell monolayer is shown (Figure 1, F-J) and exhibits a corresponding shift in the population distribution indicates increasing RSV F levels over the first day and decay in the subsequent days. Example 2 The RSV-F variant design F(ii) (Figure 2A) expresses AM14-(+) RSV F protein, as does designs, F318 and F319 (Figure 2B and 2C, respectively), and design F(i) (Figure 2D). As shown by area under the curve (AUC), the four constructs perform similarly (Figure 2E). Design F(ii), with CT deletions (in whole or in part), expresses AM14(+) RSV F to a greater degree than F(ii) parental molecule (i.e. absent CT deletions) (Figure 2A). Using F318, F319 or F(i), (Figures 2B, C and D, respectively), deletions within the CT improves RSV F AM14+ signal by at least 2x, at 24 hours post transfection. The maximal effect from CT deletion is consistently observed with 20AA deletion while 3AA deletion supersedes complete deletion of the CT (Figure 2E). Example 3 The surface expression of immunogenic RSV F may include, but is not limited to, monomeric to multimeric F states and any abundant RSV F conformations. Total expression of RSV F protein at the cell surface can be captured using the monoclonal antibody motavizumab. As shown, Motavizumab(+) RSV F variant F(ii) is readily detected 24 hours post transfection, while 3 amino acid, 20 amino acid and complete CT deletion, respectively, engineered into F protein unambiguously increases expression (Figure 3A). Similarly, the RSV F variants F318, F319 and F(i), each demonstrate substantial increases for RSV F expression when carrying CT deletions (Figure 3B, 4C & 4D, respectively). Deletions in the CT universally increase RSV F expression (Figure 3E) Example 4 The RSV F protein variants F(ii) and DS-Cav1 (Table 1), were each modelled as their respective mRNA doppelgangers for an in vivo study (Example 6). Designs F(i) and F(iii) (control) were additionally synthesized (Table 1). mRNA-based models of F(ii), F(i), F318 and F319 were created to include the CT deletion of 20 amino acids (ΔCT20) (Table 2). The total RSV F expression (Figure 4A Docket No.: 70280WO01 & C) is improved by ΔCT20. As a measure of the total, pre-fusion state, RSV F expression is increased by the ΔCT20 (Figure 4E and G). In congruence, the ΔCT20 universally improves cell surface expression of the trimeric, pre-fusion RSV F conformation (Figure 4I & K). While the level of RSV F measured varied across a broad range (Figures 4A, C, E, G, I & K), transfection of diverse mRNAs and the expressed cognate proteins did not meaningfully impact the integrity of the cell monolayers at either 24 (Figure 4B, F & J) or 67 hours post transfection (Figure 4D, H & L) and were not acutely toxic in primary cells. Example 5 Protein expression at the cell surface varied as a function of RSV F CT amino acid length. BJ cells were transfected with mRNAs encoding F(ii) RSV F protein that varied in the CT length across a range from no CT to the full length, 25AA CT (See Table 2). BJ cell monolayers were fixed at time points either 20 or 47 hours post transfection. Surface exposed, trimeric RSV F (Figure 5A) or whole-cell, prefusion RSV F (Figure 5B) was quantified by High Content imaging following immunolabeling of the fixed, BJ cells. Expression level varied according to the length of CT. For example, when assessed by AM14 binding (Figure 5A), trimeric, prefusion RSV-F expression was highest with the ΔCT20 variant (CT length of 5 residues). Example 6 – In vivo immunisation RNA encoding F(iii), F(i), F(i) ΔCT20, F(ii), F(ii) ΔCT20, DS-Cav1, F318, F318 ΔCT20, F319 or F319 ΔCT20 was administered to mice as set out in the Materials and Methods section. Figure 6 displays the RSV pre-F IgG binding antibody geometric mean titres on day 21 (3wp1) and day 35 (2wp2) in animals immunized with either 2 μg (Figure 6A) or 0.2 μg (Figure 6B) of RNA encoding F(iii), F(i), F(i) ΔCT20, F(ii), F(ii) ΔCT20, DS-Cav1, F318, F318 ΔCT20, F319, or F319 ΔCT20 (where each point represents an individual animal). There were no binding antibody responses in the saline control group (data not shown). On day 21, all constructs elicited measurable pre-F- specific IgG binding antibodies with a 2μg dose. A single dose of DS-Cav1 elicited the lowest pre-F- specific IgG binding antibodies compared to the other constructs. By day 35, all pre-F-specific IgG antibodies were boosted, and elicited similar antibody titres. The two immunizations with a 2μg dose of F318, F318 ΔCT20, F319, and F319 ΔCT20 boosted pre-F specific IgG antibodies to levels that were noninferior to the benchmark controls F(i), F(ii), F(iii) and DS-Cav1 (Figures 6 A and C-F). At the low dose, F318 ΔCT20 achieved noninferiority when compared to F(ii) and F(iii) at day 35 (2wp2) (Figures 6B, D and F). One 0.2μg dose of F318 ΔCT20 or F319 ΔCT20 elicited significantly higher pre-F IgG titres compared to the non- ΔCT20 counterparts (Figure 6B and G). Figure 7 displays the RSV A neutralising antibody titres (ED60) on day 21 (3wp1) and day 35 (2wp2) in animals immunized with either (Figure 7A) 2 μg or (Figure 7B) 0.2 μg of RNA encoding F(iii), F(i), F(i) ΔCT20, F(ii), F(ii) ΔCT20, DS-Cav1, F318, F318 ΔCT20, F319, or F319 ΔCT20 (where each point represents an individual animal). The saline group did not generate a measurable neutralisation Docket No.: 70280WO01 response to RSV A (data not shown). All neutralisation titres were boosted with a second vaccination At the high (2μg) dose, one vaccination generated measurable neutralisation to RSV A (Figure 7A). At the high (2μg dose), F318 ΔCT20, F319, and F319 ΔCT20 reached noninferiority compared to F(iii) at day 35 (2wp2) (Figure 7A and C). At the high (2μg) dose, F318 ΔCT20, F319, and F319 ΔCT20 generated significantly higher neutralisation titres compared to DS-Cav1 on day 21 (3wp1). By day 35, F318 ΔCT20, F319, and F319 ΔCT20 were noninferior to DS-Cav1 (Figure 7A and E). DS-Cav1 vaccination generated the lowest neutralisation titres with one 0.2 μg dose (Figure 7B). The effect of ΔCT20 was most prominent in the low dose (Figure 7B). neutralisAt the low (0.2μg) dose, F(ii) and F318 and F319 containing the ΔCT20 elicited higher neutralisation titres to RSV A compared to their non - ΔCT20 counterparts (Figure 7B), which was statistically significant for F318 and F319 (Figure 7E). . At the high (2μg) dose (Figure 7A, E), the impact of the ΔCT20 may have been masked due to possible saturation effects. Example 7 – Toluene nitrosulphonic acid (TNS) fluorescence assay for determining pKa Steps (1) – (14): (1) admixing 400 μL of 2 mM of the cationic lipid that is in 100 volume % ethanol and 800 μL of 0.3 mM of fluorescent probe TNS, which is in 90 volume % ethanol and 10 volume % methanol, thereby obtaining a lipid/TNS mixture; (2) admixing 7.5 μL of the lipid/TNS mixture and 242.5 μL of a first buffer comprising a sodium salt buffer comprising 20 mM sodium phosphate, 25 mM sodium citrate, 20 mM sodium acetate, and 150 mM sodium chloride, wherein the first buffer has a first pH from 4.44 to 4.52, thereby obtaining a first mixture, and dispensing 100 μL of the first mixture in a first well of a 96-well plate, which has a clear bottom; (3) admixing 7.5 μL of the lipid/TNS mixture and 242.5 μL of a second buffer comprising the sodium salt buffer, wherein the second buffer has a second pH of 5.27, thereby obtaining a second mixture, and dispensing 100 μL of the second mixture in a second well of the 96-well plate; (4) admixing 7.5 μL of the lipid/TNS mixture and 242.5 μL of a third buffer comprising the sodium salt buffer, wherein the third buffer has a third pH of from 6.15 to 6.21, thereby obtaining a third mixture, and dispensing 100 μL of the third mixture in a third well of the 96-well plate; (5) admixing 7.5 μL of the lipid/TNS mixture and 242.5 μL of a fourth buffer comprising the sodium salt buffer, wherein the fourth buffer has a fourth pH of 6.57, thereby obtaining a fourth mixture, and dispensing 100 μL of the fourth mixture in a fourth well of the 96-well plate; (6) admixing 7.5 μL of the lipid/TNS mixture and 242.5 μL of a fifth buffer comprising the sodium salt buffer, wherein the fifth buffer has a fifth pH of from 7.10 to 7.20, thereby obtaining a fifth mixture, and dispensing 100 μL of the fifth mixture in a fifth well of the 96-well plate; Docket No.: 70280WO01 (7) admixing 7.5 μL of the lipid/TNS mixture and 242.5 μL of a sixth comprising the sodium salt buffer, wherein the sixth buffer has a sixth pH of from 7.72 to 7.80, thereby obtaining a sixth mixture, and dispensing 100 μL of the sixth mixture in a sixth well of the 96-well plate; (8) admixing 7.5 μL of the lipid/TNS mixture and 242.5 μL of a seventh buffer comprising the sodium salt buffer, wherein the seventh buffer has a seventh pH of from 8.27 to 8.33, thereby obtaining a seventh mixture, and dispensing 100 μL of the seventh mixture in a seventh well of the 96-well plate; (9) admixing 7.5 μL of the lipid/TNS mixture and 242.5 μL of an eighth buffer comprising the sodium salt buffer, wherein the eighth buffer has an eighth pH of from 10.47 to 11.12, thereby obtaining an eighth mixture, and dispensing 100 μL of the eighth mixture in an eighth well of the 96-well plate; (10) measuring the absolute fluorescence at a wavelength of 431 nm with an excitation wavelength of 322 nm and a cut-off below 420 nm of each of the first through eighth wells and an empty well of the 96-well plate; (11) subtracting the absolute fluorescence of the empty well from each of the absolute fluorescence values of the first through the eighth wells, thereby obtaining a blank-subtracted fluorescence for each of the first through eighth mixtures; (12) normalising each of the blank-subtracted fluorescence values of the first through eighth mixtures to the blank-subtracted fluorescence of the first mixture, thereby obtaining a relative fluorescence for each of the first through eighth mixtures, the relative fluorescence of the first mixture being 1; (13) regressing by the Henderson-Hasselbalch equation, the first through eighth pH values versus the respective relative fluorescence values of the first through eighth mixtures thereby obtaining a line of best fit; and (14) determining the pKa as the pH at which a relative fluorescence of 0.5 is obtained on the line of best fit. Example 8 - RNA expression (further RSV-F designs) Constructs discussed in the following Example are presented below in Table 6 (a subset of Table 5 for ease of reference). Table 6 – substitutions in mRNA-encoded protein designs tested in cell-based assay (subset of Table 5) Designation mRNA construct Protein substitutions relative to wild- RSV-F design in Figures 8- designation type 10 (x axis) and Ex 8 Docket No.: 70280WO01 n/a All mRNAs encode RSV-F proteins n/a having these mutations relative to WT (SEQ ID NO: 1). Further mutations in each RSV-F design are listed below. S55T, V152R, S215A, N228K, K315I, A346Q, K445D, T455V, V459M 1) KM112 (SEQ ID S211N, S348N F217 (SEQ ID NO: 78) NO: 129) 2) KM112d20 (SEQ S211N, S348N, Δ555-574 F217d20 (SEQ ID NO: 79) ID NO: 80) 3) KM211 (SEQ ID S211N, S348N, D486C, A490C F528 (SEQ ID NO: 81) NO: 82) 8) KM223 (SEQ ID S211N, S348N, D486C, A490C, Δ555- F528d20 (SEQ NO: 91) 574 ID NO: 92) 13) KM235 (SEQ ID R712 (SEQ ID NO: 101) NO: 102) 14) KM236 (SEQ ID D486C, A490C R713 a.k.a. NO: 103) F647 (SEQ ID NO: 104) 20) KM242 (SEQ ID Δ555-574 R712d20 (SEQ NO: 115) ID NO: 116) 21) KM243 (SEQ ID D486C, A490C, Δ555-574 R713d20 a.k.a NO: 117) F647d20 (SEQ ID NO: 118) 8A RSV F immunogenicity of mRNA vaccines may be improved by optimizing post-translational features of the RSV F antigen. The parent construct, (13, Table 5), includes a full-length C-terminal domain (CTD) and was compared to the F antigen with a cytoplasmic tail (CT) truncation of 20 amino acids from the C-terminus (see 20, Table 5). Next, the F antigens (13 & 20) were evaluated in the context of two additional classes of post translational modifications. First, the addition of N-linked glycosylations was tested by mutating serine (S) 211 and 348 to asparagine (N) (see 1 & 2, Table 5). Second, the Docket No.: 70280WO01 addition of a disulphide bond was considered by mutating aspartic acid (D) 486 and alanine (A) 490 to cysteines (C) (see 14 & 21, Table 5). Finally, the F antigen designs features were also considered in combination (see 3 & 8, Table 5). All F antigens were encoded by in vitro transcribed mRNAs that include common 5’ & 3’ UTR sequences (“UTR4”), common mRNA cap structure (Cap 1), 3’ polyA tail (see sequence listing for sequence) and nucleotide chemistry (100% replacement of uridine with 1mΨ). These eight F antigen designs were evaluated in parallel using cell-based, High Content imaging assays (see materials and methods). The F antigen expression encoded by the eight candidate mRNAs was evaluated at the cell surface of primary human fibroblast (BJ) cells and readily quantified using High Content imaging. The total expression of RSV F protein (measured by motavizumab binding) was assessed 24 (Figure 10A) & 72 (Figure 10B) hours post-transfection (hpt). As expected, F antigens with a full-length CT were generally reduced in level at both time points, compared to corresponding F antigens with a truncated CTD, demonstrating the strong impact of the CT truncation on RSV F surface expression. At 24hpt (Figure 10A), the F antigen expression of the parent (13) marginally improved by addition of the glycosylations (1), and improved approximately 20% by addition of the disulphide bond (14). Two- days later, F antigen expression is mostly similar between (13), (1), (14) and (3) (Figure 10B). However, F antigen comprising the truncated CT (20) was expressed generally equivalent with (21) containing the disulphide bond, and (8) including both disulphide bond and glycosylation mutations, or modestly reduced when mutated to include additional glycosylations (2) for data at both 24hpt and 72hpt (Figure 10A and B respectively). 8B The prefusion conformation levels of RSV F protein (measured by D25 binding) were assessed 24 (Figure 9A) & 72 (Figure 9B) hours post transfection (hpt) using a cell-surface specific staining protocol. Consistent with prior results, F antigens with a full length CT were generally reduced in level at both time points, compared to corresponding F antigens with a truncated CT. At 24hpt (Figure 9A), the F antigen expression of the parent (13) improves about 30% by addition of the glycosylations (1), and improves approximately 50% by addition of the disulphide bond (14). Two- days later, F antigen expression retains the overall trends observed at 24hpt for (13), (1) and (14) (Figure 9B). 24 hpt (Figure 9A), the F antigen supported by the truncated CT (20) was expressed equivalent with (21) containing the disulphide bond, and (8) including both disulphide bond and glycosylation mutations, or modestly reduced when mutated to include additional glycosylations (2).72hpt, antigen design (21) exceeds all others, indicating the best stability for the pre-fusion conformation of the F antigen (Figure 9B). Docket No.: 70280WO01 8C The RSV F-encoding mRNAs were characterized using conformation-specific antibody AM14 that recognizes the trimeric, prefusion quaternary F antigen structure. The quaternary levels of RSV F protein (measured by AM14 binding) were assessed 24 (Figure 8A) & 72 (Figure 8B) hours post transfection (hpt) using a cell-surface specific staining protocol. Consistent with prior results, F antigens with a full length CT were generally reduced in level at both time points, compared to any F antigen models with a truncated CT. At 24hpt (Figure 8A), the F antigen expression of the parent (13) improves about 20% by addition of the glycosylations (1), and improves approximately 2x by addition of the disulphide bond (14). Two- days later, F antigen expression retains the overall trends observed at 24hpt for (13), (1), (14) and (3) (Figure 8B). 24 hpt (Figure 8A), the F antigen supported by the truncated CT (21), containing the disulphide bond, is expressed to a higher level than (20), (8), or (2). 72hpt (Figure 8B), antigen design (21) maintains superior expression of the trimeric, pre-fusion state of the F antigen. 8D When recombinant proteins were analysed by cryo-electron microscopy, the 486:490 disulphide bond in designs F528, F647 and F651 was found to form an intra-protomer disulphide bond (data not shown). Example 9 – Minimal substitution screen (recombinant protein) Constructs F301 – F307 were generated as recombinant proteins with 6 substitutions each against the RSV A2 WT background sequence (positions 1-513 of SEQ ID NO: 1). Substitutions were also individually added to RSV A2 WT background sequence to generate sequences F308 – F313 and F226 with one substitution each (see Table 7A). C-terminal sequences (positions 514 onwards) of all recombinant protein constructs were according to SEQ ID NO: 130. Table 7A – substitutions tested in minimal substitution screen Design Substitutions relative to wild-type F301 S55T, S215A, N228K, K315I, S348N, T455V F302 S55T, S215A, N228K, K315I, S348N, V459M F303 S55T, S215A, N228K, K315I, T455V, V459M F304 S55T, S215A, N228K, S348N, T455V, V459M F305 S55T, S215A, K315I, S348N, T455V, V459M F306 S55T, N228K, K315I, S348N, T455V, V459M Docket No.: 70280WO01 F307 S215A, N228K, K315I, S348N, T455V, V459M F308 S55T F309 S215A F310 N228K F311 S348N F312 T455V F313 V459M F226 K315I Mutants were produced and screened as described under Materials & Methods. All mutants in the group F301 – F307 expressed and had binding to mAbs AM14, D25, and RSB1 equivalent to DS-Cav1 (Figure 14), confirming a pre-fusion confirmation. This means a pre-fusion confirmation can be obtained with different combinations of these substitutions. Sequences F308, F309, and F311 which contained only the S55T, S215A, or S348N substitutions respectively, resulted in protein production and had some binding to mAbs AM14, D25, and RSB1 (Figures 14 & 15 respectively), though less binding than DS-Cav1. Thus, these substitutions are likely important in the stabilisation of the pre- fusion confirmation. Finally, sequence F310, containing substitution N228K had both protein expression and binding to AM14, D25, and RSB1 that was equivalent to DS-Cav1 (Figures 14 & 15 respectively), indicating that this substitution has a significant contribution to the stabilisation of pre- fusion RSV F, and is able to stabilise the pre-fusion conformation independently. F301-F307 were further characterized and showed optimal biophysical properties including thermostability similar to F225 by nano-DSF (See Table 7B, below). Long term stability of F310 was tested and is shown in Figure 23. Table 7B – Thermostability measured by nano-DSF Sample Onset Tm1 Tm2 Tm3 DS-Cav1 49.5°C 56.3°C 67.9°C 80.9°C F225 46.8°C 53.4°C 81.3°C F301 47.2°C 52.6°C 81.2°C F302 45.7°C 53.2°C 81.4°C Docket No.: 70280WO01 F303 51.4°C 57.2°C 81.7°C F304 49.9°C 54.7°C 80.8°C F305 46.5°C 52.6°C 81.2°C F306 45.9°C 53.0°C 81.6°C F307 46.3°C 52.9°C 81.4°C F310 44.0°C 56.0°C 84.2°C Example 10 – Expression in human skeletal muscle cells and dendritic cells The antigenicity of RSV-F, when delivered via nucleic acids such as RNA, may be improved and optimised for muscle cells and dendritic cells (which are particularly relevant to vaccination). Increasing total expression, and specially cell surface expression, of the protein may be used to increase antigenicity. RSV-F expression using the F(ii) construct was first assessed using human skeletal muscle cells. At 24 hours post-transfection (hpt), expression of pre-fusion RSV-F improved more than 3-fold through deletion of the C-terminal 20 amino acids (Figure 16). RSV-F expression using the F(ii) and F647 constructs was also assessed in monocyte-derived dendritic cells. At 24 hpt, expression of pre-fusion RSV-F (both constructs) improved more than 5-fold through deletion of the C-terminal 20 amino acids (Figure 17A and B). Also, expression was further improved through codon optimisation of F647-coding RNA (“F647code”; Figure 17B). Example 11 – RNA expression in vitro (further designs – minimal substitutions) Seven RSV F-encoding mRNAs with different numbers of subsitutions were screened in primary human BJ cells for their ability to express AM14-positive RSV F antigen (see Table 8, below, for mRNA and protein construct details). Measurements were taken at 24hpt. Table 8 – substitutions in mRNA-encoded protein designs tested in further cell-based assay mRNA construct designation Protein substitutions relative RSV-F design to wild-type (SEQ ID NO: 1) KM291 (SEQ ID NO: 131) S55T, S215A, N228K, D486C, F663 (SEQ ID NO: 132) A490C KM292 (SEQ ID NO: 133) S55T, S215A, N228K, D486C, F663d20 (SEQ ID NO: 134) A490C, Δ555-574 KM293 (SEQ ID NO: 135) D486C, A490C “2C” (SEQ ID NO: 136) Docket No.: 70280WO01 KM294 (SEQ ID NO: 137) D486C, A490C, Δ555-574 “2Cd20” (SEQ ID NO: 138) KM295 (SEQ ID NO: 139) WT (SEQ ID NO: 1) KM211 (SEQ ID NO: 81) S55T, V152R, S211N, S215A, F528 (SEQ ID NO: 82) N228K, K315I, A346Q, S348N, K445D, T455V, V459M, D486C, A490C KM223 (SEQ ID NO: 91) S55T, V152R, S211N, S215A, F528d20 (SEQ ID NO: 92) N228K, K315I, A346Q, S348N, K445D, T455V, V459M, D486C, A490C, Δ555-574 Results are shown in Figure 18. Highest expression was observed for F663d20 design, and lowest expression was observed for RSVF WT. Surprisingly, the “2C” RSV-F design (substitutions D486C and A490C only) exhibited higher expression than F528, when comparing like-for-like (parental and ΔCT20 versions). Example 12 – RNA expression in vitro (further designs – incremental deletions) The RSV F protein expression of F(ii) with varying CT lengths was characterized in primary human fibroblasts for the cell-surface trimeric, pre-fusion (Figure 19A, B, C) or cell-surface pre-fusion (Figure 20A, B, C) RSV F protein. See Table 9, below, for CT lengths tested. Table 9 – CT variations (incremental deletions) CT description CT AA sequence 1 Reference RSV F CT, including AA541 LIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN additional transmembrane (TM) domain (SEQ ID NO: 68) residues N-terminal to CT start 2 ΔCT3, including additional TM domain AA541 LIAVGLLLYCKARSTPVTLSKDQLSGINNIA (SEQ residues N-terminal to CT start ID NO: 69) 3 ΔCT5, including additional TM domain AA541 LIAVGLLLYCKARSTPVTLSKDQLSGINN (SEQ ID residues N-terminal to CT start NO: 70) 4 ΔCT10, including additional TM AA541 LIAVGLLLYCKARSTPVTLSKDQL (SEQ ID NO: domain residues N-terminal to CT start 71) Docket No.: 70280WO01 5 _ΔCT15, including additional TM AA541 LIAVGLLLYCKARSTPVTL (SEQ ID NO: 72) domain residues N-terminal to CT start 6 ΔCT16, including additional TM AA₅₄₁ LIAVGLLLYCKARSTPVT (positions 1-18 of SEQ ID domain residues N-terminal to CT start NO: 68) 7 ΔCT17, including additional TM AA₅₄₁ LIAVGLLLYCKARSTPV (positions 1-17 of SEQ ID domain residues N-terminal to CT start NO: 68) 8 ΔCT18, including additional TM AA₅₄₁ LIAVGLLLYCKARSTP (positions 1-16 of SEQ ID domain residues N-terminal to CT start NO: 68) 9 ΔCT19, including additional TM AA₅₄₁ LIAVGLLLYCKARST (positions 1-15 of SEQ ID NO: domain residues N-terminal to CT start 68) 1⁰ ΔCT20, including additional TM AA₅₄₁ LIAVGLLLYCKARS (positions 1-14 of SEQ ID NO: domain residues N-terminal to CT start 68) 1¹ ΔCT21, including additional TM AA541 LIAVGLLLYCKAR (positions 1-13 of SEQ ID NO: domain residues N-terminal to CT start 68) 1² ΔCT22, including additional TM AA541 LIAVGLLLYCKA (positions 1-12 of SEQ ID NO: 68) domain residues N-terminal to CT start 1³ ΔCT23, including additional TM AA541 LIAVGLLLYCK (positions 1-11 of SEQ ID NO: 68) domain residues N-terminal to CT start 1⁴ _ΔCT24, including additional TM AA541 LIAVGLLLYC (positions 1-10 of SEQ ID NO: 68) domain residues N-terminal to CT start 15 ΔCT25 (TM domain residues only) AA₅₄₁ LIAVGLLLY (positions 1-9 of SEQ ID NO: 68) In agreement with prior results (see Figure 2A), the deletion of the full-length CT (Figure 19A & 20A, see F(ii) ΔCTD) increases expression of RSV F at the cell surface compared to the parent (absent any deletions from the CT) (Figure 19A & 20A, F(ii)). The mRNA encoding CT deletion variants (Figure 19A, see F(ii) CTD Δ15, F(ii) CTD Δ15 F(ii) CTD Δ17, and F(ii) CTD Δ20) offered the best cell- surface, trimeric pre-fusion RSV F protein expression, while F(ii) CTD Δ16 offered a substantial improvement out to at least 72 hours post transfection. In contrast, both F(ii) CTD Δ21 and F(ii) ΔCTD each exhibit weaker expression (Figure 19A) for the duration of the assay. The data is summarized using area under the curve (AUC) and shown in Figures 19B & C and 20B & C. Consistent with the time-course shown in Figure 19A, the peak cell-surface, trimeric, prefusion RSV F expression is specific to variants using the CTD length at least 5 amino acids long, and in contrast, CTD lengths less than 5 amino acids are associated with reduced F protein expression (Figure 19B). Docket No.: 70280WO01 Example 13 – In vivo immunisation (further designs) RNA encoding F528, F647, F647 ΔCT20, F651 ΔCT20, F(iii), F(i), F(ii), or DS-Cav1 was administered to mice as set out in the Materials and Methods section. Figure 21 (A) presents the RSV A neutralising antibody titres (ED60) on day 21 (3wp1) and day 35 (2wp2) in animals immunized with 0.5 μg of F528, F647, F647 ΔCT20, F651 ΔCT20, F(iii), F(i), F(ii), or DS-Cav1 (where each point represents an individual animal). The saline group did not generate a measurable neutralisation response to RSV A (data not shown). On day 21, F647 ΔCT20 elicited the highest RSV A-long neutralisation antibody titres with minimal variability within the group. The neutralisation titres elicited from F647 ΔCT20 was higher than F(iii), F(i), F(iii), and DS-Cav1. Addition of a GS-linker (F651) did not substantially improve neutralisation titres. On day 35, RSV A neutralisation antibody titres from F647 d20 vaccination remained higher than F(iii), F(iii) , and DS- Cav1, and were comparable to the neutralisation titres elicited from vaccination with the F(i) antigen. Figure 21 (B) presents the RSV A and B day 35 (2wp2) cross-neutralisation titres to lab-adapted (RSV A-long and RSV B-18537) and clinical RSV strains (RSV A-Clinical 2015, RSV B-Clinical 2015 and 2017). Cross-neutralisation was improved with the F647 antigen compared to F528 and was substantially higher compared to DS-Cav1. Similar to the RSV A neutralisation results, the addition of GS-linker (F651) did not improve neutralisation titres. Overall, F647 ΔCT20 elicited consistent cross-neutralisation to all RSV A and B strains tested. Cross-neutralising antibody titres elicited from F647 ΔCT20 were higher than F(iii) and F(ii), and comparable to F(i). Finally, F647 ΔCT20 generated robust cross-neutralising titres to RSV B-Clinical 2017 strain, which contained the most mutations on the pre-F surface, indicating that the vaccine antigen can elicit neutralising antibodies to more antigenically diverse strains. Figure 22A presents the pre-F IgG binding antibody titres on day 21 and day 35. On day 21, F647 ΔCT20 generated the highest pre-F IgG antibody titres compared to F528, F647, F651 ΔCT20, F(iii), F(ii) and DS-Cav1, and the magnitude of F647 d20-elicited pre-F IgG binding antibodies were comparable to F(i) construct. By day 35, all constructs generated comparable pre-F IgG binding antibody titres. Figure 22B represents the post-F IgG binding antibody titres on day 21 and day 35. The post-F IgG binding titres were mostly comparable between all constructs tested on day 21 and day 35. The discrepancy in day 21 binding between pre-F IgG and post-F IgG antibody titres suggested that while the magnitude of antibodies that recognize the shared epitopes were comparable (as measured by post-F IgG antibodies), F647 ΔCT20 elicited a higher magnitude of antibodies that were only measurable by pre-F IgG binding and therefore this population of antibodies may be more relevant in the immunoprotective signature (including neutralising antibodies). Example 14 – Computational prediction of intra-protomer disulphide bonds in the HRB domain Structures including pdb code 5ea4 and 5c69 as well as cryo-EM structures obtained for designs F21 (mutations vs SEQ ID NO: 1 in Table 11B, below) and F216 (SEQ ID NO: 141) were prepared by Docket No.: 70280WO01 either cartesian refinement using ROSETTA Scripts and/or Quick Prep using the Molecular Operating Environment software (MOE; MOLSIS Inc., Japan). Once structures were optimised, residues within a Cβ-Cβ distance of 5Å were identified as having an optimal distance to form a disulphide bond. Residues that are within the same protomer (intra-protomer) Rwere identified. Table 11A shows residue pairs in the HRB domain (residues 474-523) that have an optimal distance in at least one of the prepared structures and were predicted to form an intra-protomer disulphide bond, based on the 5Å distance criterion. Additionally, energy calculations were then performed using MOE and the Amber15 forcefield to predict the energy stabilization resulting from each of the disulphide substitutions. Table 11A (bolded entries) shows amino acids pairs in the HRB domain identified within a Cβ-Cβ distance of 5Å, and that were predicted to be stabilising of the pre-fusion conformation in at least one of the structures analysed. These include predicted disulphide pairs that would be expected to have similar stabilising effect as the C486:C490 disulphide. Table 11A – residue pairs in the HRB domain predicted to form an intra-protomer disulphide bond, based on a 5Å distance criterion (bold = predicted to be stabilising) Y478: F483 D486: F488 D479: V482 Q/E487: A490 P480: E497 A490: Q494 L481: K501 A490: D486 V482: S502 S491: Q494 V482: I499 Q494: S485 P484: K498 E497: P480 S485: Q494 Q501: A504 D486: D489 Table 11B –substitutions relative to wild-type in “Round 1” design F21 Wildtype Position Mutant Substitution S 55 T S55T V 152 R V152R S 169 E S169E S 180 E S180E S 190 I S190I Docket No.: 70280WO01 Wildtype Position Mutant Substitution Q 210 H Q210H S 211 N S211N S 215 A S215A E 218 T E218T K 226 L K226L N 228 K N228K A 241 N A241N M 251 L M251L S 275 L S275L M 289 L M289L V 296 I V296I L 305 I L305I K 315 I K315I T 326 D T326D A 346 Q A346Q S 348 N S348N S 350 I S350I K 359 I K359I V 384 K V384K K 419 D K419D K 445 D K445D T 455 V T455V V 459 M V459M F 477 R F477R E 487 Q E487Q Docket No.: 70280WO01 Wildtype Position Mutant Substitution Q 501 K Q501K SEQUENCES SEQ ID NO: 1: Amino acid (AA) sequence of wild-type RSV-F (A2 strain) containing substitutions K66E and Q101P relative to GenBank Accession number KT992094 with full cytoplasmic tail. SEQ ID NO:1 is herein referred to as wild-type. MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 2: AA sequence of wild-type RSV-F B subtype strain 18537 (Uniprot ID: P13843) with full cytoplasmic tail. SEQ ID NO:2 is herein referred to as wild-type. MELLIHRSSAIFLTLAVNALYLTSSQNITEEFYQSTCSAVSRGYFSALRTGWYTSVITIELSNIKET KCNGTDTKVKLIKQELDKYKNAVTELQLLMQNTPAANNRARREAPQYMNYTINTTKNLNVSISKKRK RRFLGFLLGVGSAIASGIAVSKVLHLEGEVNKIKNALLSTNKAVVSLSNGVSVLTSKVLDLKNYINN RLLPIVNQQSCRISNIETVIEFQQMNSRLLEITREFSVNAGVTTPLSTYMLTNSELLSLINDMPITN DQKKLMSSNVQIVRQQSYSIMSIIKEEVLAYVVQLPIYGVIDTPCWKLHTSPLCTTNIKEGSNICLT RTDRGWYCDNAGSVSFFPQADTCKVQSNRVFCDTMNSLTLPSEVSLCNTDIFNSKYDCKIMTSKTDI SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKLEGKNLYV KGEPIINYYDPLVFPSDEFDASISQVNEKINQSLAFIRRSDELLHNVNTGKSTTNIMITTIIIVIIV VLLSLIAIGLLLYCKAKNTPVTLSKDQLSGINNIAFSK SEQ ID NO: 3: Cytoplasmic tail of SEQ ID NO: 1 (AA sequence) CKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 4: Cytoplasmic tail of SEQ ID NO: 2 (AA sequence) CKAKNTPVTLSKDQLSGINNIAFSK SEQ ID NO: 5: AM14 light chain AA sequence METPAELLFLLLLWLPDTTGDIQMTQSPSSLSASVGDRVTITCQASQDIKKYLNWYHQKPGKVPELL MHDASNLETGVPSRFSGRGSGTDFTLTISSLQPEDIGTYYCQQYDNLPPLTFGGGTKVEIKRTVAAP SVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC SEQ ID NO: 6: AM14 heavy chain AA sequence Docket No.: 70280WO01 MEFGLSWVFLVAILEGVHCEVQLVESGGGVVQPGRSLRLSCAASGFSFSHYAMHWVRQAPGKGLEWV AVISYDGENTYYADSVKGRFSISRDNSKNTVSLQMNSLRPEDTALYYCARDRIVDDYYYYGMDVWGQ GATVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLF PPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLH QDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDI AVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLS PGK SEQ ID NO: 7: D25 light chain AA sequence METPAELLFLLLLWLPDTTGDIQMTQSPSSLSAAVGDRVTITCQASQDIVNYLNWYQQKPGKAPKLL IYVASNLETGVPSRFSGSGSGTDFSLTISSLQPEDVATYYCQQYDNLPLTFGGGTKVEIKRTVAAPS VFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC SEQ ID NO: 8: D25 heavy chain AA sequence MEFGLSWVFLVAILEGVHCQVQLVQSGAEVKKPGSSVMVSCQASGGPLRNYIINWLRQAPGQGPEWM GGIIPVLGTVHYAPKFQGRVTITADESTDTAYIHLISLRSEDTAMYYCATETALVVSTTYLPHYFDN WGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV LQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSV FLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLT VLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSL SLSPGK SEQ ID NO: 9: Motavizumab light chain AA sequence METPAELLFLLLLWLPDTTGDIQMTQSPSTLSASVGDRVTITCSASSRVGYMHWYQQKPGKAPKLLI YDTSKLASGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCFQGSGYPFTFGGGTKVEIKRTVAAPSV FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKSFNRGEC SEQ ID NO: 10: Motavizumab heavy chain AA sequence MEFGLSWVFLVAILEGVHCQVTLRESGPALVKPTQTLTLTCTFSGFSLSTAGMSVGWIRQPPGKALE WLADIWWDDKKHYNPSLKDRLTISKDTSKNQVVLKVTNMDPADTATYYCARDMIFNFYFDVWGQGTT VTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPK PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDW LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVE WESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK SEQ ID NO: 11: AA sequence of exemplary F2-F1 linker sequence GSGSG SEQ ID NO: 12: AA sequence of exemplary F2-F1 linker sequence GSGSGRS SEQ ID NO: 13: AA sequence of exemplary F2-F1 linker sequence Docket No.: 70280WO01 GS SEQ ID NO: 14: AA sequence of exemplary F2-F1 linker sequence GSGSGR SEQ ID NO: 15: AA sequence of DS-CAV1 (without CT deletions) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGVAVCKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTFKVLDLKNYIDK QLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 16: AA sequence of F(ii) construct (without CT deletions) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKEI KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIPNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 17: AA sequence of F(i) construct (without CT deletions) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPACNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSACASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTIKVLDLKNYIDK QLLPIVNKQSCSISNIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYV KGEPIINFYDPLVFPSSEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 18: AA sequence of F(iii) construct (including full deletion of CT) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATGSGSAICSGVAVCKVLHLEGEVNKIKSALLS TNKAVVSLSNGVSVLTFKVLDLKNYIDKQLLPILNKQSCSISNIETVIEFQQKNNRLLEITREFSVN AGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMCIIKEEVLAYVVQLPLYG VIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSRT LPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDY VSNKGVDTVSVGNTLYCVNKQEGKSLYVKGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRK SDELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLY Docket No.: 70280WO01 SEQ ID NO: 19: AA sequence of F319 construct (without cytoplasmic tail deletions) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKHSCSIANIETVIEFQQKNKRLLEITREFSVNNGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGDTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 20: AA sequence of F318 construct (without cytoplasmic tail deletions) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO 21: AA sequence of design F216 (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKHNCSIANIETVIEFQQKNKRLLEITREFSVNNGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGDTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO 22: AA sequence of design F217 (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQNCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO: 23: AA sequence of design F224 (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNNGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV Docket No.: 70280WO01 SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO: 24: AA sequence of design F225 (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO: 25: AA sequence of design F315 (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKHNCSIANIETVIEFQQKNKRLLEITREFSVNNGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGDTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO: 26: AA sequence of design F317 (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKHSCSIANIETVIEFQQKNKRLLEITREFSVNNGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGDTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO: 27: AA sequence of design F319 (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKHSCSIANIETVIEFQQKNKRLLEITREFSVNNGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGDTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELL SEQ ID NO: 28: AA sequence of design F316 (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQNCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN Docket No.: 70280WO01 DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO: 29: AA sequence of design F318 (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO: 30: AA sequence of design F320 (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO: 31: AA sequence of design F301 (F225 substitutions minus V459M) (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNVLYYVNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO: 32: AA sequence of design F302 (F225 substitutions minus T455V) (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO: 33: AA sequence of design F303 (F225 substitutions minus S348N) (no transmembrane domain or cytoplasmic tail) Docket No.: 70280WO01 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO: 34: AA sequence of design F304 (F225 substitutions minus K315I) (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO: 35: AA sequence of design F305 (F225 substitutions minus N228K) (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO: 36: AA sequence of design F306 (F225 substitutions minus S215A) (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSISNIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO: 37: AA sequence of design F307 (F225 substitutions minus S55T) (no transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN Docket No.: 70280WO01 DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTT SEQ ID NO: 38: RNA sequence of 5’ UTR of “UTR4” (HIST2H4A 5’ UTR) – n.b., spacing to be ignored (sequence to be read as one continuous sequence) AGGAGAAGCU GUCUAUCGGG CUCCAGCGGU C SEQ ID NO: 39: RNA sequence of 3’ UTR of “UTR4” (HIST2H4A 3’ UTR) – n.b., spacing to be ignored (sequence to be read as one continuous sequence) GCCGCCGCUC CAGCUUUGCA CGUUUCGAUC CCAAAGGCCC UUUUUAGGGC CGACCA SEQ ID NO: 40: RNA sequence of 5’ UTR of “UTR3” (FAP 5’ UTR) – n.b., spacing to be ignored (sequence to be read as one continuous sequence) AGAACGCCCC CAAAAUCUGU UUCUAAUUUU ACAGAAAUCU UUUGAAACUU GGCACGGUAU UCAAAAGUCC GUGGAAAGAA AAAAACCUUG UCCUGGCUUC AGCUUCCAAC UACAAAGACA GACUUGGUCC UUUUCAACGG UUUUCACAGA UCCAGUGACC CACGCUCUGA AGACAGAAUU AGCUAACUUU CAAAAACAUC UGGAAAA SEQ ID NO: 41: RNA sequence of 3’ UTR of “UTR3” (FAP 3’ UTR) – n.b., spacing to be ignored (sequence to be read as one continuous sequence) AAACGAUGCA GAUGCAAGCC UGUAUCAGAA UCUGAAAACC UUAUAUAAAC CCCUCAGACA GUUUGCUUAU UUUAUUUUUU AUGUUGUAAA AUGCUAGUAU AAACAAACAA AUUAAUGUUG UUCUAAAGGC UGUUAAAAAA AAGAUGAGGA CUCAGAAGUU CAAGCUAAAU AUUGUUUACA UUUUCUGGUA CUCUGUGAAA GAAGAGAAAA GGGAGUCAUG CAUUUUGCUU UGGACACAGU GUUUUAUCAC CUGUUCAUUU GAAGAAAAAU AAUAAAGUCA GAAG SEQ ID NO: 42: RNA sequence of 5’ UTR of “UTR7” (IL-25’ UTR) – n.b., spacing to be ignored (sequence to be read as one continuous sequence) GUUCCCUAUC ACUCUCUUUA AUCACUACUC ACAGUAACCU CAACUCCUGC CACA SEQ ID NO: 43: RNA sequence of 3’ UTR of “UTR7” (IL-23’ UTR) – n.b., spacing to be ignored (sequence to be read as one continuous sequence) UUAAGUGCUU CCCACUUAAA ACAUAUCAGG CCUUCUAUUU AUUUAAAUAU UUAAAUUUUA UAUUUAUUGU UGAAUGUAUG GUUUGCUACC UAUUGUAACU AUUAUUCUUA AUCUUAAAAC UAUAAAUAUG GAUCUUUUAU GAUUCUUUUU GUAAGCCCUA GGGGCUCUAA AAUGGUUUCA CUUAUUUAUC CCAAAAU SEQ ID NO: 44: RNA sequence of possible 5’ UTR AGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGAGCCACC SEQ ID NO: 45: RNA sequence of possible 3’ UTR Docket No.: 70280WO01 GCUGGAGCCUCGGUGGCCAAGCUUCUUGCCCCUUGGGCCUCCCCCCAGCCCCUCCUCCCCUUCCUGC ACCCGUACCCCCGUGGUCUUUGAAUAAAGUCUGAGUGGGCGGC SEQ ID NO: 46: RNA sequence of possible 5’ UTR GAGAAUAAACUAGUAUUCUUCUGGUCCCCACAGACUCAGAGAGAACCCGCCACC SEQ ID NO: 47: RNA sequence of possible 3’ UTR CUCGAGCUGGUACUGCAUGCACGCAAUGCUAGCUGCCCCUUUCCCGUCCUGGGUACCCCGAGUCUCC CCCGACCUCGGGUCCCAGGUAUGCUCCCACCUCCACCUGCCCCACUCACCACCUCUGCUAGUUCCAG ACACCUCCCAAGCACGCAGCAAUGCAGCUCAAAACGCUUAGCCUAGCCACACCCCCACGGGAAACAG CAGUGAUUAACCUUUAGCAAUAAACGAAAGUUUAACUAAGCUAUACUAACCCCAGGGUUGGUCAAUU UCGUGCCAGCCACACCCUGGAGCUAGC SEQ ID NO: 48: RNA sequence of construct KM119 (encoding F318) – all U ribonucleotides are 1mΨ – GC content 49.70% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAUCACCAUUGAACUGUCCAACAU CAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUCAAGCAGGAGCUGGAUAAGUAUAAGAACG CCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAGCCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGG UUUAUGAACUAUACCCUGAAUAACGCCAAAAAGACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCU GGGGUUUCUGCUGGGAGUGGGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGGAACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACA UGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUGGUGUUC CCCUCUGACGAAUUCGACGCCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGGCCUUCAUUAGGAA AUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAUGAUUACCACAAUUAUCAUUG UGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGUAAGGCCAGGUCCACCCCCGUG ACCCUGUCUAAGGACCAGCUGUCUGGGAUUAAUAACAUCGCCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUU GCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 49: RNA sequence of construct KM119d3 (encoding F318d3) – all U ribonucleotides are 1mΨ – GC content 49.80% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAUCACCAUUGAACUGUCCAACAU CAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUCAAGCAGGAGCUGGAUAAGUAUAAGAACG CCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAGCCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGG UUUAUGAACUAUACCCUGAAUAACGCCAAAAAGACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCU GGGGUUUCUGCUGGGAGUGGGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAGAGU Docket No.: 70280WO01 UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGGAACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACA UGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUGGUGUUC CCCUCUGACGAAUUCGACGCCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGGCCUUCAUUAGGAA AUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAUGAUUACCACAAUUAUCAUUG UGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGUAAGGCCAGGUCCACCCCCGUG ACCCUGUCUAAGGACCAGCUGUCUGGGAUUAAUAACAUCGCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUC GAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAU GACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 50: RNA sequence of construct KM119d20 (encoding F318d20) – all U ribonucleotides are 1mΨ – GC content 49.70% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAUCACCAUUGAACUGUCCAACAU CAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUCAAGCAGGAGCUGGAUAAGUAUAAGAACG CCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAGCCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGG UUUAUGAACUAUACCCUGAAUAACGCCAAAAAGACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCU GGGGUUUCUGCUGGGAGUGGGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGGAACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACA UGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUGGUGUUC CCCUCUGACGAAUUCGACGCCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGGCCUUCAUUAGGAA AUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAUGAUUACCACAAUUAUCAUUG UGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGUAAGGCCAGGUCCUGAUAAGCC GCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAA

SEQ ID NO: 51: RNA sequence of construct KM119dCT (encoding F318dCT) – all U ribonucleotides are 1mΨ – GC content 49.60% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAUCACCAUUGAACUGUCCAACAU CAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUCAAGCAGGAGCUGGAUAAGUAUAAGAACG CCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAGCCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGG UUUAUGAACUAUACCCUGAAUAACGCCAAAAAGACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCU GGGGUUUCUGCUGGGAGUGGGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA Docket No.: 70280WO01 CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGGAACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACA UGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUGGUGUUC CCCUCUGACGAAUUCGACGCCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGGCCUUCAUUAGGAA AUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAUGAUUACCACAAUUAUCAUUG UGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGAUAAGCCGCCGCUCCAGCUUUG CACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 52: RNA sequence of construct KM120 (encoding F319) – all U ribonucleotides are 1mΨ – GC content 49.60% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAUCACCAUUGAACUGUCCAACAU CAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUCAAGCAGGAGCUGGAUAAGUAUAAGAACG CCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAGCCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGG UUUAUGAACUAUACCCUGAAUAACGCCAAAAAGACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCU GGGGUUUCUGCUGGGAGUGGGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCACAGCUG CAGCAUCGCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAAACGGCUGCUGGAGAUUACACGGGAAU UCUCCGUGAAUAACGGGGUGACAACCCCUGUGAGCACAUAUAUGCUGACAAACUCUGAACUGCUGUCUCUGAUC AACGACAUGCCAAUCACCAAUGAUCAGAAGAAACUGAUGAGCAAUAACGUGCAGAUUGUGCGGCAGCAGAGCUA CAGCAUCAUGUCCAUCAUUAAGGAAGAGGUGCUGGCCUAUGUGGUGCAGCUGCCUCUGUAUGGAGUGAUCGACA CCCCCUGUUGGAUCCUGCACACCAGCCCACUGUGCACAACCAAUACCAAAGAAGGAUCCAACAUUUGCCUGACA CGCACAGACCGCGGCUGGUACUGCGAUAAUCAGGGCAACGUGAGCUUUUUCCCUCAGGCCGAGACAUGUAAGGU GCAGAGCAACCGCGUGUUCUGUGACACCAUGAACUCCCUGACACUGCCCUCCGAAGUGAAUCUGUGUAAUGUGG ACAUCUUCAACCCCAAGUAUGACUGCAAAAUUAUGACAUCUAAGACAGACGUGUCUAGCUCUGUGAUCACCUCC CUGGGGGCCAUCGUGUCUUGUUACGGGGACACCAAGUGUACCGCCAGCAACAAGAACCGCGGCAUUAUCAAGAC AUUCAGCAACGGCUGCGAUUACGUGUCCAACAAAGGAGUGGACACCGUGUCCGUGGGUAAUGUGCUGUACUAUA UGAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUU CCUUCCGACGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAA GAGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCG UGAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGCAAAGCCAGGUCCACACCUGUG ACCCUGUCUAAGGAUCAGCUGUCUGGGAUUAACAAUAUCGCCUUUUCCAACUGAUAAGCCGCCGCUCCAGCUUU GCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 53: RNA sequence of construct KM120d3 (encoding F319d3) – all U ribonucleotides are 1mΨ – GC content 49.70% – 5’ and 3’ UTRs are “UTR4” (reference to d3, d20 and so forth, when referencing an encoded protein in the sequences, means ΔCT3, ΔCT20, and so forth). AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAUCACCAUUGAACUGUCCAACAU CAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUCAAGCAGGAGCUGGAUAAGUAUAAGAACG CCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAGCCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGG UUUAUGAACUAUACCCUGAAUAACGCCAAAAAGACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCU GGGGUUUCUGCUGGGAGUGGGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCACAGCUG CAGCAUCGCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAAACGGCUGCUGGAGAUUACACGGGAAU UCUCCGUGAAUAACGGGGUGACAACCCCUGUGAGCACAUAUAUGCUGACAAACUCUGAACUGCUGUCUCUGAUC AACGACAUGCCAAUCACCAAUGAUCAGAAGAAACUGAUGAGCAAUAACGUGCAGAUUGUGCGGCAGCAGAGCUA CAGCAUCAUGUCCAUCAUUAAGGAAGAGGUGCUGGCCUAUGUGGUGCAGCUGCCUCUGUAUGGAGUGAUCGACA Docket No.: 70280WO01 CCCCCUGUUGGAUCCUGCACACCAGCCCACUGUGCACAACCAAUACCAAAGAAGGAUCCAACAUUUGCCUGACA CGCACAGACCGCGGCUGGUACUGCGAUAAUCAGGGCAACGUGAGCUUUUUCCCUCAGGCCGAGACAUGUAAGGU GCAGAGCAACCGCGUGUUCUGUGACACCAUGAACUCCCUGACACUGCCCUCCGAAGUGAAUCUGUGUAAUGUGG ACAUCUUCAACCCCAAGUAUGACUGCAAAAUUAUGACAUCUAAGACAGACGUGUCUAGCUCUGUGAUCACCUCC CUGGGGGCCAUCGUGUCUUGUUACGGGGACACCAAGUGUACCGCCAGCAACAAGAACCGCGGCAUUAUCAAGAC AUUCAGCAACGGCUGCGAUUACGUGUCCAACAAAGGAGUGGACACCGUGUCCGUGGGUAAUGUGCUGUACUAUA UGAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUU CCUUCCGACGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAA GAGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCG UGAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGCAAAGCCAGGUCCACACCUGUG ACCCUGUCUAAGGAUCAGCUGUCUGGGAUUAACAAUAUCGCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUC GAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAU GACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 54: RNA sequence of construct KM120d20 (encoding F319d20) – all U ribonucleotides are 1mΨ – GC content 49.60% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAUCACCAUUGAACUGUCCAACAU CAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUCAAGCAGGAGCUGGAUAAGUAUAAGAACG CCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAGCCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGG UUUAUGAACUAUACCCUGAAUAACGCCAAAAAGACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCU GGGGUUUCUGCUGGGAGUGGGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCACAGCUG CAGCAUCGCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAAACGGCUGCUGGAGAUUACACGGGAAU UCUCCGUGAAUAACGGGGUGACAACCCCUGUGAGCACAUAUAUGCUGACAAACUCUGAACUGCUGUCUCUGAUC AACGACAUGCCAAUCACCAAUGAUCAGAAGAAACUGAUGAGCAAUAACGUGCAGAUUGUGCGGCAGCAGAGCUA CAGCAUCAUGUCCAUCAUUAAGGAAGAGGUGCUGGCCUAUGUGGUGCAGCUGCCUCUGUAUGGAGUGAUCGACA CCCCCUGUUGGAUCCUGCACACCAGCCCACUGUGCACAACCAAUACCAAAGAAGGAUCCAACAUUUGCCUGACA CGCACAGACCGCGGCUGGUACUGCGAUAAUCAGGGCAACGUGAGCUUUUUCCCUCAGGCCGAGACAUGUAAGGU GCAGAGCAACCGCGUGUUCUGUGACACCAUGAACUCCCUGACACUGCCCUCCGAAGUGAAUCUGUGUAAUGUGG ACAUCUUCAACCCCAAGUAUGACUGCAAAAUUAUGACAUCUAAGACAGACGUGUCUAGCUCUGUGAUCACCUCC CUGGGGGCCAUCGUGUCUUGUUACGGGGACACCAAGUGUACCGCCAGCAACAAGAACCGCGGCAUUAUCAAGAC AUUCAGCAACGGCUGCGAUUACGUGUCCAACAAAGGAGUGGACACCGUGUCCGUGGGUAAUGUGCUGACUAUAU GAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUUC CUUCCGACGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAAG AGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCGU GAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGCAAAGCCAGGUCCUGAUAAGCCG CCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAA

SEQ ID NO: 55: RNA sequence of construct KM120dCT (encoding F319dCT) – all U ribonucleotides are 1mΨ – GC content 49.60% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAUCACCAUUGAACUGUCCAACAU CAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUCAAGCAGGAGCUGGAUAAGUAUAAGAACG CCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAGCCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGG UUUAUGAACUAUACCCUGAAUAACGCCAAAAAGACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCU GGGGUUUCUGCUGGGAGUGGGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCACAGCUG CAGCAUCGCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAAACGGCUGCUGGAGAUUACACGGGAAU UCUCCGUGAAUAACGGGGUGACAACCCCUGUGAGCACAUAUAUGCUGACAAACUCUGAACUGCUGUCUCUGAUC AACGACAUGCCAAUCACCAAUGAUCAGAAGAAACUGAUGAGCAAUAACGUGCAGAUUGUGCGGCAGCAGAGCUA CAGCAUCAUGUCCAUCAUUAAGGAAGAGGUGCUGGCCUAUGUGGUGCAGCUGCCUCUGUAUGGAGUGAUCGACA CCCCCUGUUGGAUCCUGCACACCAGCCCACUGUGCACAACCAAUACCAAAGAAGGAUCCAACAUUUGCCUGACA CGCACAGACCGCGGCUGGUACUGCGAUAAUCAGGGCAACGUGAGCUUUUUCCCUCAGGCCGAGACAUGUAAGGU Docket No.: 70280WO01 GCAGAGCAACCGCGUGUUCUGUGACACCAUGAACUCCCUGACACUGCCCUCCGAAGUGAAUCUGUGUAAUGUGG ACAUCUUCAACCCCAAGUAUGACUGCAAAAUUAUGACAUCUAAGACAGACGUGUCUAGCUCUGUGAUCACCUCC CUGGGGGCCAUCGUGUCUUGUUACGGGGACACCAAGUGUACCGCCAGCAACAAGAACCGCGGCAUUAUCAAGAC AUUCAGCAACGGCUGCGAUUACGUGUCCAACAAAGGAGUGGACACCGUGUCCGUGGGUAAUGUGCUGUACUAUA UGAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUU CCUUCCGACGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAA GAGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCG UGAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGAUAAGCCGCCGCUCCAGCUUUG CACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 56: RNA sequence of construct KM173 (encoding F(i)) – all U ribonucleotides are 1mΨ – GC content 48.00% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUCGAACUGAGCAACAU CAAGGAAAAUAAGUGCAACGGGACAGACGCCAAGGUGAAACUGAUCAAGCAGGAGCUGGAUAAGUACAAGAACG CCGUGACAGAGCUGCAGCUGCUGAUGCAGUCUACACCAGCCUGCAAUAACCGCGCCCGGCGCGAACUGCCACGG UUCAUGAAUUAUACCCUGAACAAUGCCAAGAAAACAAAUGUGACACUGUCUAAGAAACGCAAGCGGAGAUUUCU GGGGUUCCUGCUGGGCGUGGGCAGCGCCUGCGCCAGCGGCGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAAUUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCUCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAAUAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUACUAUG UGAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUU CCUUCCAGCGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAA GAGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCG UGAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGCAAAGCCAGGUCCACACCUGUG ACCCUGUCUAAGGAUCAGCUGUCUGGGAUUAACAAUAUCGCCUUUUCCAACUGAUAAGCCGCCGCUCCAGCUUU GCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 57: RNA sequence of construct KM173d3 (encoding F(i) d3) – all U ribonucleotides are 1mΨ – GC content 49.30% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUCGAACUGAGCAACAU CAAGGAAAAUAAGUGCAACGGGACAGACGCCAAGGUGAAACUGAUCAAGCAGGAGCUGGAUAAGUACAAGAACG CCGUGACAGAGCUGCAGCUGCUGAUGCAGUCUACACCAGCCUGCAAUAACCGCGCCCGGCGCGAACUGCCACGG UUCAUGAAUUAUACCCUGAACAAUGCCAAGAAAACAAAUGUGACACUGUCUAAGAAACGCAAGCGGAGAUUUCU GGGGUUCCUGCUGGGCGUGGGCAGCGCCUGCGCCAGCGGCGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAAUUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCUCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAAUAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG Docket No.: 70280WO01 AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUACUAUG UGAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUU CCUUCCAGCGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAA GAGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCG UGAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGCAAAGCCAGGUCCACACCUGUG ACCCUGUCUAAGGAUCAGCUGUCUGGGAUUAACAAUAUCGCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUC GAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAU GACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 58: RNA sequence of construct KM173d20 (encoding F(i) d20) – all U ribonucleotides are 1mΨ – GC content 49.40% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUCGAACUGAGCAACAU CAAGGAAAAUAAGUGCAACGGGACAGACGCCAAGGUGAAACUGAUCAAGCAGGAGCUGGAUAAGUACAAGAACG CCGUGACAGAGCUGCAGCUGCUGAUGCAGUCUACACCAGCCUGCAAUAACCGCGCCCGGCGCGAACUGCCACGG UUCAUGAAUUAUACCCUGAACAAUGCCAAGAAAACAAAUGUGACACUGUCUAAGAAACGCAAGCGGAGAUUUCU GGGGUUCCUGCUGGGCGUGGGCAGCGCCUGCGCCAGCGGCGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAAUUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCUCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAAUAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUACUAUG UGAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUU CCUUCCAGCGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAA GAGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCG UGAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGCAAAGCCAGGUCCUGAUAAGCC GCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAA

SEQ ID NO: 59: RNA sequence of construct KM173dCT (encoding F(i) dCT) – all U ribonucleotides are 1mΨ – GC content 49.20% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUCGAACUGAGCAACAU CAAGGAAAAUAAGUGCAACGGGACAGACGCCAAGGUGAAACUGAUCAAGCAGGAGCUGGAUAAGUACAAGAACG CCGUGACAGAGCUGCAGCUGCUGAUGCAGUCUACACCAGCCUGCAAUAACCGCGCCCGGCGCGAACUGCCACGG UUCAUGAAUUAUACCCUGAACAAUGCCAAGAAAACAAAUGUGACACUGUCUAAGAAACGCAAGCGGAGAUUUCU GGGGUUCCUGCUGGGCGUGGGCAGCGCCUGCGCCAGCGGCGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAAUUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCUCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAAUAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC Docket No.: 70280WO01 CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUACUAUG UGAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUU CCUUCCAGCGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAA GAGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCG UGAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGAUAAGCCGCCGCUCCAGCUUUG CACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 60: RNA sequence of construct KM135 (encoding F(ii)) – all U ribonucleotides are 1mΨ – GC content 48.90% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUCGAACUGAGCAACAU CAAGGAAAUUAAGUGCAAUGGGACAGACGCCAAGGUGAAACUGAUCAAGCAGGAGCUGGAUAAGUACAAGAACG CCGUGACAGAGCUGCAGCUGCUGAUGCAGUCUACACCAGCCACCAAUAACCGCGCCCGGCGCGAACUGCCACGG UUCAUGAAUUAUACCCUGAACAAUGCCAAGAAAACAAAUGUGACACUGUCUAAGAAACGCAAGCGGAGAUUUCU GGGGUUCCUGCUGGGCGUGGGCAGCGCCAUUGCCAGCGGCGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCCCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAACAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUACUAUG UGAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUU CCUUCCGACGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAA GAGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCG UGAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGCAAAGCCAGGUCCACACCUGUG ACCCUGUCUAAGGAUCAGCUGUCUGGGAUUAACAAUAUCGCCUUUUCCAACUAAUAGCCGCCGCUCCAGCUUUG CACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUUUCAUUGCGCGCGCAGGCAUUGCAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAA SEQ ID NO: 61: RNA sequence of construct KM136 (encoding F(ii) d3) – all U ribonucleotides are 1mΨ – GC content 48.90% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUCGAACUGAGCAACAU CAAGGAAAUUAAGUGCAAUGGGACAGACGCCAAGGUGAAACUGAUCAAGCAGGAGCUGGAUAAGUACAAGAACG CCGUGACAGAGCUGCAGCUGCUGAUGCAGUCUACACCAGCCACCAAUAACCGCGCCCGGCGCGAACUGCCACGG UUCAUGAAUUAUACCCUGAACAAUGCCAAGAAAACAAAUGUGACACUGUCUAAGAAACGCAAGCGGAGAUUUCU GGGGUUCCUGCUGGGCGUGGGCAGCGCCAUUGCCAGCGGCGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCCCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAACAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUACUAUG Docket No.: 70280WO01 UGAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUU CCUUCCGACGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAA GAGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCG UGAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGCAAAGCCAGGUCCACACCUGUG ACCCUGUCUAAGGAUCAGCUGUCUGGGAUUAACAAUAUCGCCUAAUAGCCGCCGCUCCAGCUUUGCACGUUUCG AUCCCAAAGGCCCUUUUUAGGGCCGACCAUUUUCAUUGCGCGCGCAGGCAUUGCAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAA SEQ ID NO: 62: RNA sequence of construct KM137 (encoding F(ii) d5) – all U ribonucleotides are 1mΨ – GC content 48.90% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUCGAACUGAGCAACAU CAAGGAAAUUAAGUGCAAUGGGACAGACGCCAAGGUGAAACUGAUCAAGCAGGAGCUGGAUAAGUACAAGAACG CCGUGACAGAGCUGCAGCUGCUGAUGCAGUCUACACCAGCCACCAAUAACCGCGCCCGGCGCGAACUGCCACGG UUCAUGAAUUAUACCCUGAACAAUGCCAAGAAAACAAAUGUGACACUGUCUAAGAAACGCAAGCGGAGAUUUCU GGGGUUCCUGCUGGGCGUGGGCAGCGCCAUUGCCAGCGGCGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCCCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAACAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUACUAUG UGAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUU CCUUCCGACGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAA GAGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCG UGAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGCAAAGCCAGGUCCACACCUGUG ACCCUGUCUAAGGAUCAGCUGUCUGGGAUUAACAAUUAAUAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCA AAGGCCCUUUUUAGGGCCGACCAUUUUCAUUGCGCGCGCAGGCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 63: RNA sequence of construct KM138 (encoding F(ii) d10) – all U ribonucleotides are 1mΨ – GC content 49.00% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUCGAACUGAGCAACAU CAAGGAAAUUAAGUGCAAUGGGACAGACGCCAAGGUGAAACUGAUCAAGCAGGAGCUGGAUAAGUACAAGAACG CCGUGACAGAGCUGCAGCUGCUGAUGCAGUCUACACCAGCCACCAAUAACCGCGCCCGGCGCGAACUGCCACGG UUCAUGAAUUAUACCCUGAACAAUGCCAAGAAAACAAAUGUGACACUGUCUAAGAAACGCAAGCGGAGAUUUCU GGGGUUCCUGCUGGGCGUGGGCAGCGCCAUUGCCAGCGGCGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCCCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAACAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUAAUCUC UGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGACC UUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUACUAUGU Docket No.: 70280WO01 GAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUUC CUUCCGACGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAAG AGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCGU GAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGCAAAGCCAGGUCCACACCUGUGA CCCUGUCUAAGGAUCAGCUGUAAUAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGG CCGACCAUUUUCAUUGCGCGCGCAGGCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 64: RNA sequence of construct KM139 (encoding F(ii) d15) – all U ribonucleotides are 1mΨ – GC content 49.00% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUCGAACUGAGCAACAU CAAGGAAAUUAAGUGCAAUGGGACAGACGCCAAGGUGAAACUGAUCAAGCAGGAGCUGGAUAAGUACAAGAACG CCGUGACAGAGCUGCAGCUGCUGAUGCAGUCUACACCAGCCACCAAUAACCGCGCCCGGCGCGAACUGCCACGG UUCAUGAAUUAUACCCUGAACAAUGCCAAGAAAACAAAUGUGACACUGUCUAAGAAACGCAAGCGGAGAUUUCU GGGGUUCCUGCUGGGCGUGGGCAGCGCCAUUGCCAGCGGCGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCCCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAACAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUACUAUG UGAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUU CCUUCCGACGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAA GAGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCG UGAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGCAAAGCCAGGUCCACACCUGUG ACCCUGUAAUAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUUUCAU UGCGCGCGCAGGCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 65: RNA sequence of construct KM140 (encoding F(ii) d20) – all U ribonucleotides are 1mΨ – GC content 48.90% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUCGAACUGAGCAACAU CAAGGAAAUUAAGUGCAAUGGGACAGACGCCAAGGUGAAACUGAUCAAGCAGGAGCUGGAUAAGUACAAGAACG CCGUGACAGAGCUGCAGCUGCUGAUGCAGUCUACACCAGCCACCAAUAACCGCGCCCGGCGCGAACUGCCACGG UUCAUGAAUUAUACCCUGAACAAUGCCAAGAAAACAAAUGUGACACUGUCUAAGAAACGCAAGCGGAGAUUUCU GGGGUUCCUGCUGGGCGUGGGCAGCGCCAUUGCCAGCGGCGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCCCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAACAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUACUAUG UGAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUU Docket No.: 70280WO01 CCUUCCGACGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAA GAGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCG UGAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGCAAAGCCAGGUCCUAAUAGCCG CCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUUUCAUUGCGCGCGCAGGCAU UGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 66: RNA sequence of construct KM141 (encoding F(ii) dCT) – all U ribonucleotides are 1mΨ – GC content 48.80% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUCGAACUGAGCAACAU CAAGGAAAUUAAGUGCAAUGGGACAGACGCCAAGGUGAAACUGAUCAAGCAGGAGCUGGAUAAGUACAAGAACG CCGUGACAGAGCUGCAGCUGCUGAUGCAGUCUACACCAGCCACCAAUAACCGCGCCCGGCGCGAACUGCCACGG UUCAUGAAUUAUACCCUGAACAAUGCCAAGAAAACAAAUGUGACACUGUCUAAGAAACGCAAGCGGAGAUUUCU GGGGUUCCUGCUGGGCGUGGGCAGCGCCAUUGCCAGCGGCGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCCCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAACAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUACUAUG UGAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUU CCUUCCGACGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAA GAGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCG UGAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUAAUAGCCGCCGCUCCAGCUUUGC ACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUUUCAUUGCGCGCGCAGGCAUUGCAAAAAAAAAAAA

AAAAAAAAAAAAA SEQ ID NO: 67: RNA sequence of construct KM03 (encoding DS-Cav1) – all U ribonucleotides are 1mΨ – GC content 49.50% – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUCUGA CCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCCGUGUCU AAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUCGAACUGAGCAACAUCAAGGAAAA UAAGUGCAAUGGGACAGACGCCAAGGUGAAACUGAUCAAGCAGGAGCUGGAUAAGUACAAGAACGCCGUGACAGAGC UGCAGCUGCUGAUGCAGUCUACACCAGCCACCAAUAACCGCGCCCGGCGCGAACUGCCACGGUUCAUGAAUUAUACC CUGAACAAUGCCAAGAAAACAAAUGUGACACUGUCUAAGAAACGCAAGCGGAGAUUUCUGGGGUUCCUGCUGGGCGU GGGCAGCGCCAUUGCCAGCGGCGUGGCCGUGUGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAACAAGAUCAAGUCUG CCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUGCUGACAUUUAAGGUGCUGGAUCUG AAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUCUGAACAAGCAGAGCUGCUCCAUCUCCAACAUUGAGACCGUGAU UGAGUUUCAGCAGAAAAAUAACAGGCUGCUGGAGAUUACCAGAGAGUUCAGCGUGAACGCCGGGGUGACCACACCAG UGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAA CUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUACUCCAUCAUGUGCAUUAUCAAGGAGGAAGUGCUGGC CUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAA CCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUG AGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCU GCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCG ACGUGAGCUCUAGCGUGAUUACAUCUCUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAAC AAGAAUAGAGGCAUCAUUAAGACCUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGU GGGGAACACCCUGUACUAUGUGAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCU ACGAUCCCCUGGUGUUUCCUUCCGACGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUG Docket No.: 70280WO01 GCCUUUAUCAGAAAGAGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCAC AAUCAUUAUCGUGAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGCAAAGCCAGGUCCA CACCUGUGACCCUGUCUAAGGAUCAGCUGUCUGGGAUUAACAAUAUCGCCUUUUCCAACUAGGCCGCCGCUCCAGCU UUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 68: Reference construct C-terminus, including additional transmembrane (TM) domain residues N-terminal to CT start (AA sequence) LIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 69: CTΔ3 construct C-terminus, including additional transmembrane (TM) domain residues N-terminal to CT start (AA sequence) LIAVGLLLYCKARSTPVTLSKDQLSGINNIA SEQ ID NO: 70: CTΔ5 construct C-terminus, including additional transmembrane (TM) domain residues N-terminal to CT start (AA sequence) LIAVGLLLYCKARSTPVTLSKDQLSGINN SEQ ID NO: 71: CTΔ10 construct C-terminus, including additional transmembrane (TM) domain residues N-terminal to CT start (AA sequence) LIAVGLLLYCKARSTPVTLSKDQL SEQ ID NO: 72: CTΔ15 construct C-terminus, including additional transmembrane (TM) domain residues N-terminal to CT start (AA sequence) LIAVGLLLYCKARSTPVTL SEQ ID NO: 73: CTΔ20 construct C-terminus, including additional transmembrane (TM) domain residues N-terminal to CT start (AA sequence) LIAVGLLLYCKARS SEQ ID NO: 74: ΔCT25 construct: transmembrane (TM) domain residues only (AA sequence) LIAVGLLLY SEQ ID NO: 75: RNA sequence of construct KM126 (encoding F(iii) construct (including full deletion of CT)) – all U ribonucleotides are 1mΨ – GC content 56.40% AGGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGAGCCACCAUGGAGCUGCUGAUCCUGAAGGCCAACGC CAUCACGACCAUCCUGACCGCCGUGACCUUCUGCUUCGCCAGCGGGCAGAACAUCACCGAGGAGUUCUACCAGUCCA CCUGCUCCGCCGUGAGCAAGGGCUACCUGUCUGCCCUGAGAACCGGCUGGUACACCAGCGUGAUCACCAUCGAGCUG UCCAACAUCAAGGAGAACAAGUGCAACGGCACCGACGCCAAGGUGAAGCUGAUCAAGCAGGAGCUGGACAAGUACAA GAACGCAGUGACCGAGCUGCAGCUGCUGAUGCAGAGCACACCAGCCACCGGUAGCGGGUCCGCCAUUUGCUCCGGCG UGGCCGUGUGCAAGGUGCUGCACCUGGAGGGCGAGGUGAACAAGAUCAAGAGCGCCCUGCUCUCCACCAACAAGGCC GUGGUGAGCCUGAGCAACGGGGUGAGCGUGCUGACCUUCAAGGUGCUGGACCUGAAGAACUACAUCGACAAGCAGCU GCUGCCUAUCCUGAACAAGCAGAGCUGCAGCAUCAGCAACAUCGAGACCGUGAUCGAGUUCCAGCAGAAGAACAACC GGCUGCUGGAGAUCACCAGGGAGUUCAGCGUGAACGCAGGGGUGACCACACCCGUGUCCACCUACAUGCUGACCAAC UCCGAGCUGCUGAGCCUGAUCAACGAUAUGCCCAUCACCAACGACCAGAAGAAGCUGAUGAGCAACAACGUGCAGAU CGUGCGGCAGCAGUCCUACUCCAUCAUGUGCAUCAUCAAGGAGGAGGUGCUGGCCUACGUGGUGCAGCUGCCCCUGU ACGGCGUGAUCGACACCCCUUGCUGGAAGCUGCACACCAGCCCUCUGUGCACCACCAACACGAAGGAGGGCAGCAAU AUCUGCCUGACCCGGACCGACAGGGGCUGGUACUGCGACAACGCCGGCAGCGUGUCCUUCUUUCCCCAGGCCGAGAC CUGCAAGGUGCAGUCCAACAGGGUGUUCUGCGACACCAUGAACUCUCGCACCCUGCCCAGCGAGGUGAACCUGUGCA Docket No.: 70280WO01 ACGUGGACAUCUUCAACCCCAAGUACGACUGCAAGAUCAUGACCUCCAAGACCGACGUGUCCUCUAGCGUUAUCACC UCCCUGGGCGCCAUCGUGAGCUGCUACGGCAAGACCAAGUGCACCGCCAGCAACAAGAACAGGGGCAUCAUCAAGAC CUUCAGCAACGGGUGCGACUACGUGUCCAACAAGGGCGUGGACACCGUGUCCGUGGGCAACACCCUGUACUGCGUGA ACAAGCAGGAGGGCAAGAGCCUGUACGUGAAGGGCGAGCCCAUCAUCAACUUCUACGACCCUCUGGUGUUCCCCAGC GACGAGUUCGACGCCAGCAUCUCCCAGGUGAACGAGAAGAUCAACCAGAGCCUGGCCUUCAUCCGCAAGAGCGACGA GCUGCUGCACAACGUGAACGCCGGCAAGAGCACCACAAACAUCAUGAUCACCACCAUCAUCAUCGUGAUAAUCGUGA UCCUGCUGUCCCUGAUCGCUGUGGGCCUGCUGCUGUACUGAUAAUAGGCUGGAGCCUCGGUGGCCAUGCUUCUUGCC CCUUGGGCCUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUAAAGUCUGAGUGGGC GGCUUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 76: RNA sequence of construct XW02 (encoding DS-Cav1 construct used in in vivo study) – all U ribonucleotides are 1mΨ – GC content 49.40%% AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUCGAACUGAGCAACAU CAAGGAAAAUAAGUGCAAUGGGACAGACGCCAAGGUGAAACUGAUCAAGCAGGAGCUGGAUAAGUACAAGAACG CCGUGACAGAGCUGCAGCUGCUGAUGCAGUCUACACCAGCCACCAAUAACCGCGCCCGGCGCGAACUGCCACGG UUCAUGAAUUAUACCCUGAACAAUGCCAAGAAAACAAAUGUGACACUGUCUAAGAAACGCAAGCGGAGAUUUCU GGGGUUCCUGCUGGGCGUGGGCAGCGCCAUUGCCAGCGGCGUGGCCGUGUGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUUUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUCUGAACAAGCAGAGCUG CUCCAUCUCCAACAUUGAGACCGUGAUUGAGUUUCAGCAGAAAAAUAACAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGUGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUACUAUG UGAACAAGCAGGAAGGCAAGAGCCUGUACGUGAAGGGGGAGCCCAUCAUUAAUUUCUACGAUCCCCUGGUGUUU CCUUCCGACGAAUUCGAUGCCUCCAUCUCCCAGGUGAACGAAAAGAUCAAUCAGAGCCUGGCCUUUAUCAGAAA GAGCGAUGAACUGCUGCAUAAUGUGAAUGCCGGCAAAUCCACCACAAACAUUAUGAUUACCACAAUCAUUAUCG UGAUCAUUGUGAUUCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGCAAAGCCAGGUCCACACCUGUG ACCCUGUCUAAGGAUCAGCUGUCUGGGAUUAACAAUAUCGCCUUUUCCAACUAGCCGCCGCUCCAGCUUUGCAC GUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUUUCAUUGCGCGCGCAGGCAUUGCAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 77: AA sequence of design F225; linker sequences, T4 fibritin foldon trimerisation domain, thrombin cleavage site, strep tag and His-tag at C-terminus MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLSAIGGYIPEAPRDGQAYVRKDGE WVLLSTFLGGLVPRGGSAGSGWSHPQFEKGGGSGGGSGGGSWSHPQFEKGSKGGHHHHHH SEQ ID NO: 78: RNA sequence of construct KM112 (encoding F217) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) Docket No.: 70280WO01 AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGGUUUAUGAACUAUACCCUGAAUAACGCCAAAAA GACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCUGGGGUUUCUGCUGGGAGUGGGCUCC GCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAACAAGAUCAAGU CUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUGCUGACAUCUAA GGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAACUGCUCC AUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAG AGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCU GAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUU GUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGC UGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAA CACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGG AACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUUUUGCGAUACAA UGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAACCCAAAGUAUGA UUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGGGCGCCAUUGUG AGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGACCUUCAGCA ACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACAU GAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUG GUGUUCCCCUCUGACGAAUUCGACGCCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGG CCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAU GAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUG UAUUGUAAGGCCAGGUCCACCCCCGUGACCCUGUCUAAGGACCAGCUGUCUGGGAUUAAUAACAUCG CCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGC CGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 79: RNA sequence of construct KM112d20 (encoding F217d20) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGGUUUAUGAACUAUACCCUGAAUAACGCCAAAAA GACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCUGGGGUUUCUGCUGGGAGUGGGCUCC GCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAACAAGAUCAAGU CUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUGCUGACAUCUAA GGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAACUGCUCC AUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAG AGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCU GAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUU GUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGC UGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAA CACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGG AACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUUUUGCGAUACAA UGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAACCCAAAGUAUGA UUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGGGCGCCAUUGUG Docket No.: 70280WO01 AGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGACCUUCAGCA ACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACAU GAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUG GUGUUCCCCUCUGACGAAUUCGACGCCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGG CCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAU GAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUG UAUUGUAAGGCCAGGUCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUU UUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 80: Full length AA sequence of design F217d20 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQNCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARS SEQ ID NO: 81: RNA sequence of construct KM211 (encoding F528) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGGUUUAUGAACUAUACCCUGAAUAACGCCAAAAA GACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCUGGGGUUUCUGCUGGGAGUGGGCUCC GCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAACAAGAUCAAGU CUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUGCUGACAUCUAA GGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAACUGCUCC AUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAG AGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCU GAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUU GUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGC UGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAA CACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGG AACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUUUUGCGAUACAA UGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAACCCAAAGUAUGA UUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGGGCGCCAUUGUG AGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGACCUUCAGCA ACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACAU Docket No.: 70280WO01 GAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUG GUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGG CCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAU GAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUG UAUUGUAAGGCCAGGUCCACCCCCGUGACCCUGUCUAAGGACCAGCUGUCUGGGAUUAAUAACAUCG CCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGC CGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 82: Full length AA sequence of design F528 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQNCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 83: RNA sequence of construct KM212 (encoding R701) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGGUUUAUGAACUAUACCCUGAAUAACGCCAAAAA GACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCUGGGGUUUCUGCUGGGAGUGGGCUCC GCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAACAAGAUCAAGU CUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUGCUGACAUCUAA GGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGCCGUGCUCC AUCGCCCCGAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAG AGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCU GAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUU GUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGC UGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAA CACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGG AACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUUUUGCGAUACAA UGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAACCCAAAGUAUGA UUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGGGCGCCAUUGUG AGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGACCUUCAGCA ACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACAU GAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUG GUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGG CCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAU Docket No.: 70280WO01 GAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUG UAUUGUAAGGCCAGGUCCACCCCCGUGACCCUGUCUAAGGACCAGCUGUCUGGGAUUAAUAACAUCG CCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGC CGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 84: Full length AA sequence of design R701 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQPCSIAPIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 85: RNA sequence of construct KM213 (encoding R702) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCGGCAGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAA CAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGC AGAACUGCUCCAUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGA GAUUACCAGAGAGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAAC UCCGAGCUGCUGAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACA AUGUGCAGAUUGUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUA CGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUG UGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCG ACAAUCAGGGGAACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUU UUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAAC CCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGG GCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAA GACCUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUG CUGUAUUACAUGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUU ACGACCCCCUGGUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAA CCAGUCUCUGGCCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACC ACAAAUAUCAUGAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGG GGCUGCUGCUGUAUUGUAAGGCCAGGUCCACCCCCGUGACCCUGUCUAAGGACCAGCUGUCUGGGAU UAAUAACAUCGCCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCC CUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA Docket No.: 70280WO01 SEQ ID NO: 86: Full length AA sequence of design R702 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPAGSSAIASGRAVSKVLHLEGEVNKIKSALLSTN KAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQNCSIANIETVIEFQQKNKRLLEITREFSVNAG VTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVI DTPCWILHTSPLCTTNTKEGSNICLTRTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLP SEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVS NDGVDTVSVGNVLYYMNKQEGKSLYVKGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSD ELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 87: RNA sequence of construct KM214 (encoding R703) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAGGCAGCGGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGA GGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUG UCUGUGCUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGA ACAAGCAGAACUGCUCCAUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCU GCUGGAGAUUACCAGAGAGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUG ACCAACUCCGAGCUGCUGAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGU CUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCU GGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCU CCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGU ACUGCGACAAUCAGGGGAACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAG GGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUC UUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAU CUCUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAU CAUUAAGACCUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGG AACGUGCUGUAUUACAUGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUA ACUUUUACGACCCCCUGGUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAA AAUUAACCAGUCUCUGGCCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAG AGCACCACAAAUAUCAUGAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUG CCGUGGGGCUGCUGCUGUAUUGUAAGGCCAGGUCCACCCCCGUGACCCUGUCUAAGGACCAGCUGUC UGGGAUUAAUAACAUCGCCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCA AAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAU GACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 88: Full length AA sequence of design R703 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATGSGSAIASGRAVSKVLHLEGEVNKIKSALLS TNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQNCSIANIETVIEFQQKNKRLLEITREFSVN AGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYG Docket No.: 70280WO01 VIDTPCWILHTSPLCTTNTKEGSNICLTRTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLT LPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDY VSNDGVDTVSVGNVLYYMNKQEGKSLYVKGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRK SDELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 89: RNA sequence of construct KM215 (encoding R704) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGGUUUAUGAACUAUACCCUGAAUAACGCCAAAAA GACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCUGGGGUUUCUGCUGGGAGUGGGCUCC GCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAACAAGAUCAAGU CUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUGCUGACAUCUAA GGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUGCUCC AUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAG AGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCU GAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUU GUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGC UGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAA CACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGG AACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUUUUGCGAUACAA UGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAACCCAAAGUAUGA UUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGGGCGCCAUUGUG AGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGACCUUCAGCA ACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACAU GAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUG GUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGG CCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAU GAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUG UAUUGUAAGGCCAGGUCCACCCCCGUGACCCUGUCUAAGGACCAGCUGUCUGGGAUUAAUAACAUCG CCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGC CGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 90: Full length AA sequence of design R704 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV Docket No.: 70280WO01 SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 91: RNA sequence of construct KM223 (encoding F528d20) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGGUUUAUGAACUAUACCCUGAAUAACGCCAAAAA GACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCUGGGGUUUCUGCUGGGAGUGGGCUCC GCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAACAAGAUCAAGU CUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUGCUGACAUCUAA GGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAACUGCUCC AUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAG AGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCU GAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUU GUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGC UGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAA CACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGG AACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUUUUGCGAUACAA UGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAACCCAAAGUAUGA UUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGGGCGCCAUUGUG AGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGACCUUCAGCA ACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACAU GAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUG GUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGG CCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAU GAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUG UAUUGUAAGGCCAGGUCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUU UUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 92: Full length AA sequence of design F528d20 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQNCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARS Docket No.: 70280WO01 SEQ ID NO: 93: RNA sequence of construct KM224 (encoding R701d20) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGGUUUAUGAACUAUACCCUGAAUAACGCCAAAAA GACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCUGGGGUUUCUGCUGGGAGUGGGCUCC GCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAACAAGAUCAAGU CUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUGCUGACAUCUAA GGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGCCGUGCUCC AUCGCCCCGAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAG AGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCU GAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUU GUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGC UGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAA CACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGG AACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUUUUGCGAUACAA UGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAACCCAAAGUAUGA UUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGGGCGCCAUUGUG AGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGACCUUCAGCA ACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACAU GAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUG GUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGG CCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAU GAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUG UAUUGUAAGGCCAGGUCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUU UUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 94: Full length AA sequence of design R701d20 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQPCSIAPIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARS SEQ ID NO: 95: RNA sequence of construct KM225 (encoding R702d20) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) Docket No.: 70280WO01 AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCGGCAGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAA CAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGC AGAACUGCUCCAUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGA GAUUACCAGAGAGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAAC UCCGAGCUGCUGAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACA AUGUGCAGAUUGUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUA CGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUG UGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCG ACAAUCAGGGGAACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUU UUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAAC CCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGG GCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAA GACCUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUG CUGUAUUACAUGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUU ACGACCCCCUGGUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAA CCAGUCUCUGGCCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACC ACAAAUAUCAUGAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGG GGCUGCUGCUGUAUUGUAAGGCCAGGUCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCC AAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUA UGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 96: Full length AA sequence of design R702d20 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPAGSSAIASGRAVSKVLHLEGEVNKIKSALLSTN KAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQNCSIANIETVIEFQQKNKRLLEITREFSVNAG VTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVI DTPCWILHTSPLCTTNTKEGSNICLTRTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLP SEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVS NDGVDTVSVGNVLYYMNKQEGKSLYVKGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSD ELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARS SEQ ID NO: 97: RNA sequence of construct KM226 (encoding R703d20) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAGGCAGCGGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGA Docket No.: 70280WO01 GGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUG UCUGUGCUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGA ACAAGCAGAACUGCUCCAUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCU GCUGGAGAUUACCAGAGAGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUG ACCAACUCCGAGCUGCUGAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGU CUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCU GGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCU CCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGU ACUGCGACAAUCAGGGGAACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAG GGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUC UUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAU CUCUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAU CAUUAAGACCUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGG AACGUGCUGUAUUACAUGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUA ACUUUUACGACCCCCUGGUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAA AAUUAACCAGUCUCUGGCCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAG AGCACCACAAAUAUCAUGAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUG CCGUGGGGCUGCUGCUGUAUUGUAAGGCCAGGUCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUC GAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 98: Full length AA sequence of design R703d20 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATGSGSAIASGRAVSKVLHLEGEVNKIKSALLS TNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQNCSIANIETVIEFQQKNKRLLEITREFSVN AGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYG VIDTPCWILHTSPLCTTNTKEGSNICLTRTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLT LPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDY VSNDGVDTVSVGNVLYYMNKQEGKSLYVKGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRK SDELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARS SEQ ID NO: 99: RNA sequence of construct KM227 (encoding R704d20) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGGUUUAUGAACUAUACCCUGAAUAACGCCAAAAA GACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCUGGGGUUUCUGCUGGGAGUGGGCUCC GCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAACAAGAUCAAGU CUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUGCUGACAUCUAA GGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUGCUCC AUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAG AGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCU GAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUU Docket No.: 70280WO01 GUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGC UGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAA CACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGG AACGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUUUUGCGAUACAA UGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAACCCAAAGUAUGA UUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGGGCGCCAUUGUG AGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGACCUUCAGCA ACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACAU GAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUG GUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGG CCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAU GAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUG UAUUGUAAGGCCAGGUCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUU UUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 100: Full length AA sequence of design R704d20 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARS SEQ ID NO: 101: RNA sequence of construct KM235 (encoding R712) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGGUUUAUGAACUAUACCCUGAAUAACGCCAAAAA GACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCUGGGGUUUCUGCUGGGAGUGGGCUCC GCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAACAAGAUCAAGU CUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUGCUGACAUCUAA GGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUGCUCC AUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAG AGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCU GAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUU GUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGC UGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAA CACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGG AGCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUUUUGCGAUACAA Docket No.: 70280WO01 UGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAACCCAAAGUAUGA UUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGGGCGCCAUUGUG AGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGACCUUCAGCA ACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACAU GAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUG GUGUUCCCCUCUGACGAAUUCGACGCCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGG CCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAU GAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUG UAUUGUAAGGCCAGGUCCACCCCCGUGACCCUGUCUAAGGACCAGCUGUCUGGGAUUAAUAACAUCG CCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGC CGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 102: Full length AA sequence of design R712 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 103: RNA sequence of construct KM236 (encoding R713) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGGUUUAUGAACUAUACCCUGAAUAACGCCAAAAA GACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCUGGGGUUUCUGCUGGGAGUGGGCUCC GCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAACAAGAUCAAGU CUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUGCUGACAUCUAA GGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUGCUCC AUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAG AGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCU GAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUU GUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGC UGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAA CACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGG AGCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUUUUGCGAUACAA UGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAACCCAAAGUAUGA UUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGGGCGCCAUUGUG AGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGACCUUCAGCA ACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACAU GAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUG Docket No.: 70280WO01 GUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGG CCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAU GAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUG UAUUGUAAGGCCAGGUCCACCCCCGUGACCCUGUCUAAGGACCAGCUGUCUGGGAUUAAUAACAUCG CCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGC CGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 104: Full length AA sequence of design R713 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 105: RNA sequence of construct KM237 (encoding R714) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGGUUUAUGAACUAUACCCUGAAUAACGCCAAAAA GACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCUGGGGUUUCUGCUGGGAGUGGGCUCC GCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAACAAGAUCAAGU CUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUGCUGACAUCUAA GGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGCCGUGCUCC AUCGCCCCGAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAG AGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCU GAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUU GUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGC UGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAA CACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGG AGCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUUUUGCGAUACAA UGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAACCCAAAGUAUGA UUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGGGCGCCAUUGUG AGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGACCUUCAGCA ACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACAU GAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUG GUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGG Docket No.: 70280WO01 CCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAU GAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUG UAUUGUAAGGCCAGGUCCACCCCCGUGACCCUGUCUAAGGACCAGCUGUCUGGGAUUAAUAACAUCG CCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGC CGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 106: Full length AA sequence of design R714 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQPCSIAPIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 107: RNA sequence of construct KM238 (encoding R715) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCGGCAGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAA CAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGC AGAGCUGCUCCAUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGA GAUUACCAGAGAGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAAC UCCGAGCUGCUGAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACA AUGUGCAGAUUGUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUA CGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUG UGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCG ACAAUCAGGGGAGCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUU UUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAAC CCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGG GCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAA GACCUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUG CUGUAUUACAUGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUU ACGACCCCCUGGUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAA CCAGUCUCUGGCCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACC ACAAAUAUCAUGAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGG GGCUGCUGCUGUAUUGUAAGGCCAGGUCCACCCCCGUGACCCUGUCUAAGGACCAGCUGUCUGGGAU UAAUAACAUCGCCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCC Docket No.: 70280WO01 CUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 108: Full length AA sequence of design R715 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPAGSSAIASGRAVSKVLHLEGEVNKIKSALLSTN KAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAG VTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVI DTPCWILHTSPLCTTNTKEGSNICLTRTDRGWYCDNQGSVSFFPQAETCKVQSNRVFCDTMNSLTLP SEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVS NDGVDTVSVGNVLYYMNKQEGKSLYVKGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSD ELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 109: RNA sequence of construct KM239 (encoding R716) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAGGCAGCGGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGA GGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUG UCUGUGCUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGA ACAAGCAGAGCUGCUCCAUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCU GCUGGAGAUUACCAGAGAGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUG ACCAACUCCGAGCUGCUGAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGU CUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCU GGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCU CCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGU ACUGCGACAAUCAGGGGAGCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAG GGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUC UUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAU CUCUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAU CAUUAAGACCUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGG AACGUGCUGUAUUACAUGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUA ACUUUUACGACCCCCUGGUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAA AAUUAACCAGUCUCUGGCCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAG AGCACCACAAAUAUCAUGAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUG CCGUGGGGCUGCUGCUGUAUUGUAAGGCCAGGUCCACCCCCGUGACCCUGUCUAAGGACCAGCUGUC UGGGAUUAAUAACAUCGCCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCA AAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAU GACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 110: Full length AA sequence of design R716 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATGSGSAIASGRAVSKVLHLEGEVNKIKSALLS Docket No.: 70280WO01 TNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVN AGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYG VIDTPCWILHTSPLCTTNTKEGSNICLTRTDRGWYCDNQGSVSFFPQAETCKVQSNRVFCDTMNSLT LPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDY VSNDGVDTVSVGNVLYYMNKQEGKSLYVKGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRK SDELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 111: RNA sequence of construct KM240 (encoding R717) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCGGCAGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAA CAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGC AGCCGUGCUCCAUCGCCCCGAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGA GAUUACCAGAGAGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAAC UCCGAGCUGCUGAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACA AUGUGCAGAUUGUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUA CGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUG UGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCG ACAAUCAGGGGAGCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUU UUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAAC CCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGG GCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAA GACCUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUG CUGUAUUACAUGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUU ACGACCCCCUGGUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAA CCAGUCUCUGGCCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACC ACAAAUAUCAUGAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGG GGCUGCUGCUGUAUUGUAAGGCCAGGUCCACCCCCGUGACCCUGUCUAAGGACCAGCUGUCUGGGAU UAAUAACAUCGCCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCC CUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 112: Full length AA sequence of design R717 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPAGSSAIASGRAVSKVLHLEGEVNKIKSALLSTN KAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQPCSIAPIETVIEFQQKNKRLLEITREFSVNAG VTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVI DTPCWILHTSPLCTTNTKEGSNICLTRTDRGWYCDNQGSVSFFPQAETCKVQSNRVFCDTMNSLTLP SEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVS Docket No.: 70280WO01 NDGVDTVSVGNVLYYMNKQEGKSLYVKGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSD ELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 113: RNA sequence of construct KM241 (encoding R718) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAGGCAGCGGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGA GGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUG UCUGUGCUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGA ACAAGCAGCCGUGCUCCAUCGCCCCGAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCU GCUGGAGAUUACCAGAGAGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUG ACCAACUCCGAGCUGCUGAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGU CUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCU GGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCU CCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGU ACUGCGACAAUCAGGGGAGCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAG GGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUC UUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAU CUCUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAU CAUUAAGACCUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGG AACGUGCUGUAUUACAUGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUA ACUUUUACGACCCCCUGGUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAA AAUUAACCAGUCUCUGGCCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAG AGCACCACAAAUAUCAUGAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUG CCGUGGGGCUGCUGCUGUAUUGUAAGGCCAGGUCCACCCCCGUGACCCUGUCUAAGGACCAGCUGUC UGGGAUUAAUAACAUCGCCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCA AAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAU GACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 114: Full length AA sequence of design R718 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATGSGSAIASGRAVSKVLHLEGEVNKIKSALLS TNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQPCSIAPIETVIEFQQKNKRLLEITREFSVN AGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYG VIDTPCWILHTSPLCTTNTKEGSNICLTRTDRGWYCDNQGSVSFFPQAETCKVQSNRVFCDTMNSLT LPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDY VSNDGVDTVSVGNVLYYMNKQEGKSLYVKGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRK SDELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 115: RNA sequence of construct KM242 (encoding R712d20) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) Docket No.: 70280WO01 AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGGUUUAUGAACUAUACCCUGAAUAACGCCAAAAA GACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCUGGGGUUUCUGCUGGGAGUGGGCUCC GCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAACAAGAUCAAGU CUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUGCUGACAUCUAA GGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUGCUCC AUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAG AGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCU GAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUU GUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGC UGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAA CACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGG AGCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUUUUGCGAUACAA UGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAACCCAAAGUAUGA UUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGGGCGCCAUUGUG AGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGACCUUCAGCA ACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACAU GAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUG GUGUUCCCCUCUGACGAAUUCGACGCCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGG CCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAU GAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUG UAUUGUAAGGCCAGGUCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUU UUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 116: Full length AA sequence of design R712d20 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARS SEQ ID NO: 117: RNA sequence of construct KM243 (encoding R713d20) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC Docket No.: 70280WO01 AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGGUUUAUGAACUAUACCCUGAAUAACGCCAAAAA GACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCUGGGGUUUCUGCUGGGAGUGGGCUCC GCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAACAAGAUCAAGU CUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUGCUGACAUCUAA GGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUGCUCC AUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAG AGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCU GAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUU GUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGC UGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAA CACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGG AGCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUUUUGCGAUACAA UGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAACCCAAAGUAUGA UUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGGGCGCCAUUGUG AGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGACCUUCAGCA ACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACAU GAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUG GUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGG CCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAU GAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUG UAUUGUAAGGCCAGGUCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUU UUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 118: Full length AA sequence of design R713d20 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARS SEQ ID NO: 119: RNA sequence of construct KM244 (encoding R714d20) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGGUUUAUGAACUAUACCCUGAAUAACGCCAAAAA GACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCUGGGGUUUCUGCUGGGAGUGGGCUCC GCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAACAAGAUCAAGU Docket No.: 70280WO01 CUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUGCUGACAUCUAA GGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGCCGUGCUCC AUCGCCCCGAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAG AGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCU GAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUU GUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGC UGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUGUGCACAACCAA CACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCGACAAUCAGGGG AGCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUUUUGCGAUACAA UGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAACCCAAAGUAUGA UUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGGGCGCCAUUGUG AGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGACCUUCAGCA ACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUGCUGUAUUACAU GAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUG GUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGG CCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAU GAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUG UAUUGUAAGGCCAGGUCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUU UUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 120: Full length AA sequence of design R714d20 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQPCSIAPIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARS SEQ ID NO: 121: RNA sequence of construct KM245 (encoding R715d20) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCGGCAGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAA CAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGC AGAGCUGCUCCAUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGA GAUUACCAGAGAGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAAC UCCGAGCUGCUGAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACA AUGUGCAGAUUGUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUA Docket No.: 70280WO01 CGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUG UGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCG ACAAUCAGGGGAGCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUU UUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAAC CCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGG GCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAA GACCUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUG CUGUAUUACAUGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUU ACGACCCCCUGGUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAA CCAGUCUCUGGCCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACC ACAAAUAUCAUGAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGG GGCUGCUGCUGUAUUGUAAGGCCAGGUCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCC AAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUA UGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 122: Full length AA sequence of design R715d20 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPAGSSAIASGRAVSKVLHLEGEVNKIKSALLSTN KAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAG VTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVI DTPCWILHTSPLCTTNTKEGSNICLTRTDRGWYCDNQGSVSFFPQAETCKVQSNRVFCDTMNSLTLP SEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVS NDGVDTVSVGNVLYYMNKQEGKSLYVKGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSD ELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARS SEQ ID NO: 123: RNA sequence of construct KM245 (encoding R716d20) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAGGCAGCGGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGA GGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUG UCUGUGCUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGA ACAAGCAGAGCUGCUCCAUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCU GCUGGAGAUUACCAGAGAGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUG ACCAACUCCGAGCUGCUGAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGU CUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCU GGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCU CCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGU ACUGCGACAAUCAGGGGAGCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAG GGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUC UUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAU CUCUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAU CAUUAAGACCUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGG Docket No.: 70280WO01 AACGUGCUGUAUUACAUGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUA ACUUUUACGACCCCCUGGUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAA AAUUAACCAGUCUCUGGCCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAG AGCACCACAAAUAUCAUGAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUG CCGUGGGGCUGCUGCUGUAUUGUAAGGCCAGGUCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUC GAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 124: Full length AA sequence of design R716d20 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATGSGSAIASGRAVSKVLHLEGEVNKIKSALLS TNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVN AGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYG VIDTPCWILHTSPLCTTNTKEGSNICLTRTDRGWYCDNQGSVSFFPQAETCKVQSNRVFCDTMNSLT LPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDY VSNDGVDTVSVGNVLYYMNKQEGKSLYVKGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRK SDELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARS SEQ ID NO: 125: RNA sequence of construct KM247 (encoding R717d20) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCGGCAGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGAGGUGAA CAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGC AGCCGUGCUCCAUCGCCCCGAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGA GAUUACCAGAGAGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAAC UCCGAGCUGCUGAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACA AUGUGCAGAUUGUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUA CGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCUCCACUG UGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGUACUGCG ACAAUCAGGGGAGCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAGGGUGUU UUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUCUUCAAC CCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCUCUGG GCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAA GACCUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGGAACGUG CUGUAUUACAUGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUU ACGACCCCCUGGUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAA CCAGUCUCUGGCCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACC ACAAAUAUCAUGAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGG GGCUGCUGCUGUAUUGUAAGGCCAGGUCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUCGAUCCC AAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAGCAUA UGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA Docket No.: 70280WO01 SEQ ID NO: 126: Full length AA sequence of design R717d20 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPAGSSAIASGRAVSKVLHLEGEVNKIKSALLSTN KAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQPCSIAPIETVIEFQQKNKRLLEITREFSVNAG VTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVI DTPCWILHTSPLCTTNTKEGSNICLTRTDRGWYCDNQGSVSFFPQAETCKVQSNRVFCDTMNSLTLP SEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVS NDGVDTVSVGNVLYYMNKQEGKSLYVKGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSD ELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARS SEQ ID NO: 127: RNA sequence of construct KM248 (encoding R718d20) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” (underlined) AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACA ACCAUUCUGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGU CCACCUGCUCCGCCGUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAU CACCAUUGAACUGUCCAACAUCAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUC AAGCAGGAGCUGGAUAAGUAUAAGAACGCCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAG CCACAGGCAGCGGCUCCGCCAUCGCCUCCGGACGCGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCGA GGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUG UCUGUGCUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGA ACAAGCAGCCGUGCUCCAUCGCCCCGAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCU GCUGGAGAUUACCAGAGAGUUCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUG ACCAACUCCGAGCUGCUGAGCCUGAUUAACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGU CUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUACUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCU GGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACACCCCUUGUUGGAUUCUGCACACAUCU CCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACAAGAACCGACAGAGGCUGGU ACUGCGACAAUCAGGGGAGCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGUGCAGUCCAACAG GGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGGAUAUC UUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAU CUCUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAU CAUUAAGACCUUCAGCAACGGAUGUGACUAUGUGUCCAAUGACGGCGUGGACACAGUGUCUGUGGGG AACGUGCUGUAUUACAUGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUA ACUUUUACGACCCCCUGGUGUUCCCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAA AAUUAACCAGUCUCUGGCCUUCAUUAGGAAAUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAG AGCACCACAAAUAUCAUGAUUACCACAAUUAUCAUUGUGAUCAUUGUGAUCCUGCUGUCUCUGAUUG CCGUGGGGCUGCUGCUGUAUUGUAAGGCCAGGUCCUGAUAAGCCGCCGCUCCAGCUUUGCACGUUUC GAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 128: Full length AA sequence of design R718d20 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATGSGSAIASGRAVSKVLHLEGEVNKIKSALLS TNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQPCSIAPIETVIEFQQKNKRLLEITREFSVN Docket No.: 70280WO01 AGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYG VIDTPCWILHTSPLCTTNTKEGSNICLTRTDRGWYCDNQGSVSFFPQAETCKVQSNRVFCDTMNSLT LPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDY VSNDGVDTVSVGNVLYYMNKQEGKSLYVKGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRK SDELLHNVNAGKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARS SEQ ID NO: 129: Full length AA sequence of design F217 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQNCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 130: C-terminus (position 514 onwards) of recombinant protein constructs used in Example 9 (linker sequences, T4 fibritin foldon trimerisation domain, thrombin cleavage site, strep tag and His-tag) SAIGGYIPEAPRDGQAYVRKDGEWVLLSTFLGGLVPRGGSAGSGWSHPQFEKGGGSGGGSGGGSWSH PQFEKGSKGGHHHHHH SEQ ID NO: 131: RNA sequence of construct KM291 (encoding F663) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAUCACCAUUGAACUGUCCAACAU CAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUCAAGCAGGAGCUGGAUAAGUAUAAGAACG CCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAGCCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGG UUUAUGAACUAUACCCUGAAUAACGCCAAAAAGACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCU GGGGUUUCUGCUGGGAGUGGGCUCCGCCAUCGCCUCCGGAGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUAUUACG UGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUGGUGUUC CCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGGCCUUCAUUAGGAA AUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAUGAUUACCACAAUUAUCAUUG Docket No.: 70280WO01 UGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGUAAGGCCAGGUCCACCCCCGUG ACCCUGUCUAAGGACCAGCUGUCUGGGAUUAAUAACAUCGCCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUU GCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 132: Full length AA sequence of design F663 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKQSCSIANIETVIEFQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLT RTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSNKGVDTVSVGNTLYYVNKQEGKSLYV KGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSDELLHNVNAGKSTTNIMITTIIIVIIV ILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 133: RNA sequence of construct KM292 (encoding F663d20) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAACCGUGAUCACCAUUGAACUGUCCAACAU CAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUCAAGCAGGAGCUGGAUAAGUAUAAGAACG CCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAGCCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGG UUUAUGAACUAUACCCUGAAUAACGCCAAAAAGACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCU GGGGUUUCUGCUGGGAGUGGGCUCCGCCAUCGCCUCCGGAGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCGCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAGAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUAUUACG UGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUGGUGUUC CCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGGCCUUCAUUAGGAA AUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAUGAUUACCACAAUUAUCAUUG UGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGUAAGGCCAGGUCCUGAUAAGCC GCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAA

SEQ ID NO: 134: Full length AA sequence of design F663d20 Docket No.: 70280WO01 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKENKCNGTDA KVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAI ASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSIANIETVIE FQQKNKRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEV LAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTM NSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSN KGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSDELLHNVNA GKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARS SEQ ID NO: 135: RNA sequence of construct KM293 (encoding 2C) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUUGAACUGUCCAACAU CAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUCAAGCAGGAGCUGGAUAAGUAUAAGAACG CCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAGCCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGG UUUAUGAACUAUACCCUGAAUAACGCCAAAAAGACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCU GGGGUUUCUGCUGGGAGUGGGCUCCGCCAUCGCCUCCGGAGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCUCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAUAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUAUUACG UGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUGGUGUUC CCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGGCCUUCAUUAGGAA AUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAUGAUUACCACAAUUAUCAUUG UGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGUAAGGCCAGGUCCACCCCCGUG ACCCUGUCUAAGGACCAGCUGUCUGGGAUUAAUAACAUCGCCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUU GCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 136: Full length AA sequence of design 2C MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDA KVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAI ASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSISNIETVIE FQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEV LAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTM NSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSN KGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSDELLHNVNA GKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARSTPVTLSKDQLSGINNIAFSN SEQ ID NO: 137: RNA sequence of construct KM294 (encoding 2Cd20) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” Docket No.: 70280WO01 AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUUGAACUGUCCAACAU CAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUCAAGCAGGAGCUGGAUAAGUAUAAGAACG CCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAGCCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGG UUUAUGAACUAUACCCUGAAUAACGCCAAAAAGACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCU GGGGUUUCUGCUGGGAGUGGGCUCCGCCAUCGCCUCCGGAGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCUCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAUAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUAUUACG UGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUGGUGUUC CCCUCUUGCGAAUUCGACUGCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGGCCUUCAUUAGGAA AUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAUGAUUACCACAAUUAUCAUUG UGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGUAAGGCCAGGUCCUGAUAAGCC GCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAA

SEQ ID NO: 138: Full length AA sequence of design 2Cd20 MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTSVITIELSNIKENKCNGTDA KVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRKRRFLGFLLGVGSAI ASGVAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDKQLLPIVNKQSCSISNIETVIE FQQKNNRLLEITREFSVNAGVTTPVSTYMLTNSELLSLINDMPITNDQKKLMSNNVQIVRQQSYSIMSIIKEEV LAYVVQLPLYGVIDTPCWKLHTSPLCTTNTKEGSNICLTRTDRGWYCDNAGSVSFFPQAETCKVQSNRVFCDTM NSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDVSSSVITSLGAIVSCYGKTKCTASNKNRGIIKTFSNGCDYVSN KGVDTVSVGNTLYYVNKQEGKSLYVKGEPIINFYDPLVFPSCEFDCSISQVNEKINQSLAFIRKSDELLHNVNA GKSTTNIMITTIIIVIIVILLSLIAVGLLLYCKARS SEQ ID NO: 139: RNA sequence of construct KM294 (encoding WT) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAAGCCAACGCCAUUACAACCAUUC UGACCGCCGUGACCUUUUGCUUCGCCAGCGGCCAGAACAUUACCGAAGAGUUCUACCAGUCCACCUGCUCCGCC GUGUCUAAAGGCUACCUGUCCGCCCUGAGAACCGGAUGGUACACAAGCGUGAUCACCAUUGAACUGUCCAACAU CAAAGAGAACAAGUGUAACGGCACCGACGCCAAAGUGAAGCUGAUCAAGCAGGAGCUGGAUAAGUAUAAGAACG CCGUGACAGAACUGCAGCUGCUGAUGCAGUCUACCCCAGCCACAAAUAACCGCGCCCGCCGGGAGCUGCCAAGG UUUAUGAACUAUACCCUGAAUAACGCCAAAAAGACCAACGUGACCCUGAGCAAGAAACGCAAGCGCCGGUUCCU GGGGUUUCUGCUGGGAGUGGGCUCCGCCAUCGCCUCCGGAGUGGCCGUGAGCAAAGUGCUGCAUCUGGAAGGCG AGGUGAACAAGAUCAAGUCUGCCCUGCUGUCCACAAACAAGGCCGUGGUGUCUCUGAGCAACGGGGUGUCUGUG CUGACAUCUAAGGUGCUGGAUCUGAAAAAUUAUAUUGAUAAACAGCUGCUGCCAAUUGUGAACAAGCAGAGCUG CUCCAUCUCCAACAUCGAGACCGUGAUUGAGUUUCAGCAGAAGAACAAUAGGCUGCUGGAGAUUACCAGAGAGU UCAGCGUGAACGCCGGGGUGACCACACCAGUGUCUACAUACAUGCUGACCAACUCCGAGCUGCUGAGCCUGAUU AACGACAUGCCCAUCACAAACGAUCAGAAGAAACUGAUGUCUAACAAUGUGCAGAUUGUGCGGCAGCAGUCUUA CUCCAUCAUGAGCAUUAUCAAGGAGGAAGUGCUGGCCUACGUGGUGCAGCUGCCUCUGUAUGGGGUGAUCGACA CCCCUUGUUGGAAGCUGCACACAUCUCCACUGUGCACAACCAACACCAAGGAAGGAAGCAAUAUCUGUCUGACA AGAACCGACAGAGGCUGGUACUGCGACAAUGCCGGGUCCGUGAGCUUCUUUCCCCAGGCCGAGACCUGCAAGGU Docket No.: 70280WO01 GCAGUCCAACAGGGUGUUUUGCGAUACAAUGAAUAGCCUGACCCUGCCCUCCGAGGUGAACCUGUGUAACGUGG AUAUCUUCAACCCAAAGUAUGAUUGCAAAAUCAUGACCAGCAAGACCGACGUGAGCUCUAGCGUGAUUACAUCU CUGGGCGCCAUUGUGAGCUGUUAUGGAAAGACAAAGUGUACCGCCUCCAACAAGAAUAGAGGCAUCAUUAAGAC CUUCAGCAACGGAUGUGACUAUGUGUCCAAUAAAGGCGUGGACACAGUGUCUGUGGGGAACACCCUGUAUUACG UGAACAAGCAGGAGGGAAAGUCCCUGUACGUGAAAGGGGAGCCUAUCAUUAACUUUUACGACCCCCUGGUGUUC CCCUCUGACGAAUUCGACGCCUCUAUCUCCCAGGUGAAUGAAAAAAUUAACCAGUCUCUGGCCUUCAUUAGGAA AUCUGACGAGCUGCUGCACAAUGUGAAUGCCGGCAAGAGCACCACAAAUAUCAUGAUUACCACAAUUAUCAUUG UGAUCAUUGUGAUCCUGCUGUCUCUGAUUGCCGUGGGGCUGCUGCUGUAUUGUAAGGCCAGGUCCACCCCCGUG ACCCUGUCUAAGGACCAGCUGUCUGGGAUUAAUAACAUCGCCUUCUCUAAUUGAUAAGCCGCCGCUCCAGCUUU GCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO: 140: RNA sequence of construct KM289 (encoding R713d20; codon optimised) – all U ribonucleotides are 1mΨ – 5’ and 3’ UTRs are “UTR4” AGGAGAAGCUGUCUAUCGGGCUCCAGCGGUCAUGGAGCUGCUGAUCCUGAAGGCCAACGCCAUCACCACCAUCC UGACCGCCGUGACCUUCUGCUUCGCCUCCGGCCAGAACAUCACCGAGGAGUUCUACCAGUCCACCUGCAGCGCC GUGUCCAAGGGCUACCUGUCCGCCCUGCGGACCGGCUGGUACACCACCGUGAUCACCAUCGAGCUGUCCAACAU CAAGGAGAACAAGUGCAACGGCACCGACGCCAAGGUGAAGCUGAUCAAGCAGGAGCUGGACAAGUACAAGAACG CCGUGACCGAGCUGCAGCUGCUGAUGCAGUCCACCCCCGCCACCAACAACCGGGCCCGGCGGGAGCUGCCCCGG UUCAUGAACUACACCCUGAACAACGCCAAGAAGACCAACGUGACCCUGUCCAAGAAGCGGAAGCGGCGGUUCCU GGGCUUCCUGCUGGGCGUGGGCUCCGCCAUCGCCUCCGGCCGGGCCGUGUCCAAGGUGCUGCACCUGGAGGGCG AGGUGAACAAGAUCAAGUCCGCCCUGCUGUCCACCAACAAGGCCGUGGUGUCCCUGUCCAACGGCGUGUCCGUG CUGACCAGCAAGGUGCUGGACCUGAAGAACUACAUCGACAAGCAGCUGCUGCCCAUCGUGAACAAGCAGAGCUG CUCCAUCGCCAACAUCGAGACCGUGAUCGAGUUCCAGCAGAAGAACAAGCGGCUGCUGGAGAUCACCCGGGAGU UCUCCGUGAACGCCGGCGUGACCACCCCCGUGUCCACCUACAUGCUGACCAACUCCGAGCUGCUGUCCCUGAUC AACGACAUGCCCAUCACCAACGACCAGAAGAAGCUGAUGAGCAACAACGUGCAGAUCGUGCGGCAGCAGUCCUA CAGCAUCAUGUCCAUCAUCAAGGAGGAGGUGCUGGCCUACGUGGUGCAGCUGCCCCUGUACGGCGUGAUCGACA CCCCCUGCUGGAUCCUGCACACCUCCCCCCUGUGCACCACCAACACCAAGGAGGGCAGCAACAUCUGCCUGACC CGGACCGACCGGGGCUGGUACUGCGACAACCAGGGCUCCGUGUCCUUCUUCCCCCAGGCCGAGACCUGCAAGGU GCAGUCCAACCGGGUGUUCUGCGACACCAUGAACUCCCUGACCCUGCCCUCCGAGGUGAACCUGUGCAACGUGG ACAUCUUCAACCCCAAGUACGACUGCAAGAUCAUGACCUCCAAGACCGACGUGUCCUCCUCCGUGAUCACCUCC CUGGGCGCCAUCGUGUCCUGCUACGGCAAGACCAAGUGCACCGCCUCCAACAAGAACCGGGGCAUCAUCAAGAC CUUCUCCAACGGCUGCGACUACGUGUCCAACGACGGCGUGGACACCGUGUCCGUGGGCAACGUGCUGUACUACA UGAACAAGCAGGAGGGCAAGUCCCUGUACGUGAAGGGCGAGCCCAUCAUCAACUUCUACGACCCCCUGGUGUUC CCCUCCUGCGAGUUCGACUGCUCCAUCAGCCAGGUGAACGAGAAGAUCAACCAGAGCCUGGCCUUCAUCCGGAA GUCCGACGAGCUGCUGCACAACGUGAACGCCGGCAAGUCCACCACCAACAUCAUGAUCACCACCAUCAUCAUCG UGAUCAUCGUGAUCCUGCUGUCCCUGAUCGCCGUGGGCCUGCUGCUGUACUGCAAGGCCCGGUCCUGAUAAGCC GCCGCUCCAGCUUUGCACGUUUCGAUCCCAAAGGCCCUUUUUAGGGCCGACCAUUCAUUGCAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAGCAUAUGACUAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA SEQ ID NO 141: AA sequence of design F216 (no foldon, transmembrane domain or cytoplasmic tail) MELLILKANAITTILTAVTFCFASGQNITEEFYQSTCSAVSKGYLSALRTGWYTTVITIELSNIKEN KCNGTDAKVKLIKQELDKYKNAVTELQLLMQSTPATNNRARRELPRFMNYTLNNAKKTNVTLSKKRK RRFLGFLLGVGSAIASGRAVSKVLHLEGEVNKIKSALLSTNKAVVSLSNGVSVLTSKVLDLKNYIDK QLLPIVNKHNCSIANIETVIEFQQKNKRLLEITREFSVNNGVTTPVSTYMLTNSELLSLINDMPITN DQKKLMSNNVQIVRQQSYSIMSIIKEEVLAYVVQLPLYGVIDTPCWILHTSPLCTTNTKEGSNICLT RTDRGWYCDNQGNVSFFPQAETCKVQSNRVFCDTMNSLTLPSEVNLCNVDIFNPKYDCKIMTSKTDV SSSVITSLGAIVSCYGDTKCTASNKNRGIIKTFSNGCDYVSNDGVDTVSVGNVLYYMNKQEGKSLYV KGEPIINFYDPLVFPSDEFDASISQVNEKINQSLAFIRKSDELL SEQ ID NO: 142: Deletion of 20 residues from the C-terminal end of SEQ ID NO: 3 Docket No.: 70280WO01 TPVTLSKDQLSGINNIAFSN SEQ ID NO: 143: Deletion of 20 residues from the C-terminal end of SEQ ID NO: 4 TPVTLSKDQLSGINNIAFSK [1] Rha et al. Pediatrics.2020 Jul;146(1):e20193611 [2] Falsey et al. N Engl J Med.2005 Apr 28;352(17):1749-59. [3] Falsey and Walsh. Clin Microbiol Rev.2000;13:371–84. [4] Groothuis et al. Adv Ther 2011;28:110-25. [5] Feltes et al. Pediatr Res 2011; 70:186-91. [6] Carbonell-Estrany et al. Pediatrics 2010;125:e35–51. [7] O’Brien et al. Lancet Infect Dis 2015;15:1398-408. [8] The IMpact-RSV study group. Pediatrics 1998;102:531-537. [9] Krarup et al. Nat Commun.2015 Sep 3;6:8143. [10] https://www.gsk.com/en-gb/media/press-releases/gsk-s-older-adult-respiratory-syncytial-virus- rsv-vaccine-candidate/ [11] https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-top- line-data-phase-3-trial-older [12] Whitehead et al. Journal of Virology.1998;72(5) [13] Sievers et al. Methods Mol Biol.2014;1079:105-16. [14] Gilman et al. PLOSPathogens.2015; 11(7), e1005035 [15] McLellan et al. Science.2013.340, 6136.1113-7 [16] Lucas et al. 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Claims

Docket No.: 70280WO01 CLAIMS 1. A recombinant ribonucleic acid (RNA) encoding a respiratory syncytial virus fusion (RSV-F) protein comprising a cytoplasmic tail; wherein, relative to a cytoplasmic tail according to SEQ ID NO: 3 or 4, 2-20 residues are deleted from the C-terminal end of the cytoplasmic tail of the RSV- F protein; and wherein the RNA has a guanine-cytosine (GC) content of 30-70%. 2. The RNA of claim 1, wherein 2-5, 2-4, 2-3, 3-4 or 3 residues are deleted from the C-terminal end of the cytoplasmic tail of the RSV-F protein. 3. The RNA of claim 1 or 2, wherein the cytoplasmic tail comprises (i) an amino acid sequence according to positions 10-31 of SEQ ID NO: 69, or (ii) an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% identical to said positions and optionally the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). 4. The RNA of claim 1, wherein 6-13, 7-13, 8-12, 9-11, 9-10, 10-11 or 10 residues are deleted from the C-terminal end of the cytoplasmic tail of the RSV-F protein. 5. The RNA of claim 1 or 4, wherein the cytoplasmic tail comprises (i) an amino acid sequence according to positions 10-24 of SEQ ID NO: 71, or (ii) an amino acid sequence at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% identical to said positions and optionally the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). 6. The RNA of claim 1, wherein 14-16, 14-15 or 15-16, or 15 residues are deleted from the C-terminal end of the cytoplasmic tail of the RSV-F protein. 7. The RNA of claim 1 or 6, wherein the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-19 of SEQ ID NO: 72, or (ii) an amino acid sequence at least 60%, 70%, 80% or 90% identical to said positions and optionally the same length as said positions; and wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii) 8. The RNA of claim 1, wherein 16-20, 17-20, 18-20 or 19-20 residues are deleted from the C- terminal end of the cytoplasmic tail of the RSV-F protein. 9. The RNA of claim 8, wherein 20 residues are deleted from the C-terminal end of the cytoplasmic tail of the RSV-F protein. 10. The RNA of claim 1, 8 or 9, wherein the cytoplasmic tail comprises or consists of (i) an amino acid sequence according to positions 10-14 of SEQ ID NO: 73, or (ii) an amino acid sequence at least 60% or 80% identical to said positions and optionally the same length as said positions; and Docket No.: 70280WO01 wherein the cytoplasmic tail does not comprise any residues C-terminal to the amino acid sequence of (i) or (ii). 11. The RNA of any preceding claim, wherein the RSV-F protein comprises an ectodomain comprising an F2 and an F1 domain, and a substitution relative to a wild-type RSV-F ectodomain, such as positions 26-109 and 137-523 of SEQ ID NO: 1 or 2, of a residue for a C residue in both of the F2 and F1 domains, introducing a disulphide bond between said C residues when the RSV-F protein is expressed. 12. The RNA of claim 11, wherein the ectodomain comprises the substitutions 103C, 148C, 190I, and 486S. 13. The RNA of any of claims 1-10, wherein the RSV-F protein comprises an ectodomain comprising substitutions relative to a wild-type RSV-F ectodomain, such as positions 26-109 and 137-523 of SEQ ID NO: 1 or 2, and wherein the substitutions are selected from: (i) 55T, 152R, 215A, 228K, 315I, 346Q, 445D, 455V and 459M (ii) 55T, 152R, 211N, 215A, 228K, 315I, 346Q, 348N, 445D, 455V and 459M; (iii) 55T, 152R, 210H, 211N, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 445D, 455V and 459M; (iv) 55T, 215A, 228K, 241N, 315I, 348N, 455V and 459M; (v) 55T, 215A, 228K, 315I, 348N, 455V and 459M; (vi) 55T, 215A, 228K, 315I, 348N, 455V and 459M; (vii) 55T, 152R, 210H, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 445D, 455V and 459M; (viii) 55T, 152R, 210H, 215A, 228K, 241N, 315I, 346Q, 348N, 419D, 455V and 459M; (ix) 55T, 152R, 211N, 215A, 228K, 315I, 346Q, 348N, 455V and 459M; (x) 55T, 152R, 215A, 228K, 315I, 346Q, 348N, 445D, 455V and 459M; or (xi) 55T, 152R, 215A, 228K, 315I, 346Q, 348N, 455V and 459M. 14. The RNA of any preceding claim, wherein the RSV-F protein comprises an amino acid sequence having at least 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to positions 1-549 of SEQ ID NO: 1; optionally wherein the RSV-F protein is of the A subtype. 15. The RNA of any of claims 1-13, wherein the RSV-F protein comprises an amino acid sequence having at least 80%, 81% 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity to positions 1-549 of SEQ ID NO: 2; optionally wherein the RSV-F protein is of the B subtype. 16. The RNA of any of preceding claim, having a GC content of 40-70% or 45-70%. Docket No.: 70280WO01 17. The RNA of any of preceding claim, comprising, in the 5’ to 3’ direction: a 5’ Cap, a 5’ UTR, an open reading frame encoding the RSV-F protein, a 3’UTR, and a 3’ poly-A tail. 18. The RNA of any of preceding claim, comprising a modified ribonucleotide, optionally wherein the modified ribonucleotide is 1mΨ. 19. The RNA of claim 18, wherein the RNA comprises 1mΨ and neither standard U ribonucleotides nor other modified U ribonucleotides; optionally wherein the RNA comprises 1mΨ and neither standard U ribonucleotides nor other modified ribonucleotides. 20. A lipid nanoparticle comprising the RNA of any of preceding claim. 21. A pharmaceutical composition comprising the RNA of any of claims 1-19, or lipid nanoparticle of claim 20; optionally for use in medicine. 22. The pharmaceutical composition for use of claim 21, for use in a method of vaccinating a subject against RSV; optionally wherein the subject is: a human infant, optionally 2-6 months old; a human older adult, optionally ≥50 or ≥60 years old; or a pregnant human female, optionally ≥28 weeks pregnant. 23. A method of inducing an immune response against RSV in a subject, comprising administering to the subject an immunologically effective amount of the RNA of any of claims 1-19, lipid nanoparticle of claim 20 or pharmaceutical composition of claim 21.