WO2009130479A2 - Virus - Google Patents

Abstract

The invention provides an attenuated virus.

Description

VIRUS

Field of the Invention

The present invention relates to attenuated viruses for use in vaccination.

Background to the Invention

The different tissues within an organism regularly exhibit varied gene expression and this variation is crucial to tissue and cell identity. The level of protein produced in a tissue from any given gene can be controlled at multiple points prior to translation in both the nucleus and cytoplasm. The recent discovery that an entire network of small non-coding RNA molecules (typically 21 -23 nucleotides in length) called microRNAs exists within cells added another level of control to gene regulation. MicroRNAs have been shown to negatively regulate gene expression post-transcription through a number of mechanisms which all involve binding of the microRNA to complementary regions within a messenger RNA (mRNA). Such binding sites usually reside within the 3' un-translated region (UTR) of a transcript; however, they have also been discovered within exons and the 5' UTR. Following microRNA binding, translation is inhibited either by direct interactions between microRNA machinery and translation machinery, mRNA sequestration to P bodies or by an increase in mRNA turnover due to increased degradation. Efficient repression is probably a consequence of more than one of these mechanisms.

Some microRNA genes show distinct tissue or cell type expression and their transcripts cannot be found in other tissue lineages. This allows efficient down- regulation in specific cell types and can be integral to their function and identity. This property has previously been exploited to efficiently regulate the expression of a factor IX transgene cassette.

Summary of the Invention

The invention concerns the use of microRNA binding sites to prevent virus infection and/or replication in vulnerable cells and tissues, thereby improving safety and efficacy of vaccination. By incorporating binding sites to microRNAs that are expressed in disease-associated tissues, viral replication can be decreased, restricted, or entirely ablated, to allow safer vaccination. The invention is of particular utility where viral infections compromise or kill cells that are normally involved in producing an immune response, since protection of these cells while allowing infection to proceed in less important cells should enable effective vaccination against viral pathogens that previously could not be subject to prophylactic vaccination.

Accordingly, the present invention provides a virus for use in a method of vaccination of a host, which virus is attenuated by means of a microRNA binding sequence which is present within the genome of the virus, wherein attenuation is achieved by the microRNA binding sequence causing a reduction in the level of virus replication in host cells which express a microRNA that binds to the microRNA binding sequence of the virus. hi one embodiment the virus is one which when present in a cell in which it is able to replicate, expresses at least one (for example at least 2, 3, 4 or more) mRNA molecule that comprises a microRNA binding site.

Detailed Description of the Invention

The inventors have found that limiting the infectious tropism of viruses may be used to produce safer and more effective attenuated vaccines. The viruses are modified to substantially reduce their rate of replication in a cell which is important in causing disease in the host. Preferably the virus is able to replicate in other cells, for example at rate which is similar to (or the same as) the wild-type virus, and this replication leads to an immune response against the virus.

It is to be understood that the term "binding sequence" mentioned herein includes a sequence which can directly bind to a microRNA (for example when the relevant sequence is present in an mRNA). However, unless the context requires otherwise, the term also includes the complement of such a binding sequence or any sequence which when expressed as RNA would lead to the generation of a sequence which is capable of binding microRNA, i.e. the term includes sense and antisense sequences in the genomes of viruses (in positive or negative strands) which correspond to sequences capable of binding microRNA. Vaccination/Stimulation of an Immune Response

The invention relates to attenuating a virus for use in vaccination of a host. The vaccination may be prophylactic or therapeutic, and typically causes the host to have: (i) decreased susceptibility to infection by the wild-type form of the virus and/or (ii) decreased susceptibility to disease caused by the wild-type form of the virus and/or

(iii) decreased disease symptoms when infected by the wild-type form of the virus.

The vaccination may thus be protective against infection and/or disease. The invention also relates to use of the attenuated virus of the invention for stimulating an immune response in a host, for example stimulating an antibody and/or T cell response directed against the virus. The virus of the invention is typically administered in a form in which at least some of the viruses that are administered are capable of normal or attenuated replication in at least one cell type of the host (i.e. a live vaccine). However the invention is also applicable to a "killed vaccine" where the virus preparation has been subject to a treatment which should render all of the viruses incapable of replicating in any cell of the host. Introduction of microRNA binding sites into viruses for use in a killed vaccine will enhance the safety of such vaccines.

The Host Human or Animal

The host is an animal (including birds), preferably a mammal. The host may be a human or any of any of the groups or species mentioned below:

Ungulates - Family: Suidae, Genus: Sue (Pigs)

Family Bovidae, Sub family: Bovinae, Genus: Bos (Cows) Family: Bovidae, Sub family: Carpinae, Genus: Ovis (Sheep) Family: Equidae, Genus: Equus (Horses)

Primates: Order: Primates, Sub order: Haplorrhini (Including Simian Monkeys), Sub family: Homininae (Gorillas, Chimpanzees) Tribe: Hominini (Humans)

Other: Family: Canidae, Genus: Canis. (Dogs) Family: Felidae, Genus: Felis (Cats)

Non-tetrapod chordates: Class: Actinopterygii (Fish) Class: Aves, Order: Galliformes (Land fowl), and Order: Anseriformes (Water Fowl) Family: Muridae (Rats, Gerbils, Mice, Hamsters) The host may be at (increased) risk of infection by the virus, or at (increased) risk of disease caused by the virus. The host may or may not inhabit a region for which the virus is endemic. The host may live in a population which includes individuals infected with (or carrying) the wild-type virus. The host may visit regions where the wild type virus is endemic and other individuals are carrying the virus or infected with it. The host may be an infant (for example less than 5, 3 or 1 year old) or may be old (for example more than 60, 70 or 80) years old. The host may be immunocompromised. The host typically has more than one cell type, for example at least 2, 3, 4, 5 or more cell types in which the virus is able to replicate.

The Virus of the Invention

This invention is applicable to any virus which in its wild-type form can act as a pathogen, i.e. which will typically be capable of infecting a host in its wild-type form. Thus the wild-type form of the virus will generally be capable of productively infecting at least one cell type of the host. The wild-type virus may be deleterious to the host, for example causing a disease (which has symptoms). The wild-type virus may be one which is capable of causing incapacitation or death of the host.

The virus may have a single or double stranded RNA genome either in negative or positive sense. The virus may have a single or double stranded DNA genome. The virus may have a segmented or non-segmented genome. The virus may have linear or circular genome which may or may not be covalently closed.

The virus of the invention typically replicates at reduced levels in at least 1, 2, 3 or more different cell types (of the host) in which the wild-type virus can replicate. Typically the rate of replication is reduced by at least 70%, or at least 80%, 90% or 95% or at least 99% in such a cell type. Even in such a cell type the production of certain virus proteins (themselves insufficient to permit replication) may be unaffected and may continue at normal levels. In one embodiment the virus does not replicate at all in the relevant cell. Typically replication is reduced in a cell which is normally killed by the virus in natural infection and/or the cell may be one whose loss, or change in function after virus infection, contributes to disease symptoms or death of the host. The cell may be of a cell type in which the majority of viral load is present (e.g. at least 80% or 90%) in a natural infection with the wild- type virus.

Cell types in which viral replication is reduced are preferably of importance to the metabolic, nutritional, nervous, locomotory or immune functioning of the host. They normally represent an important site of pathology during infection with the wild type virus. Suppression of viral replication in any of the following cell lineages and types may preferably be used in the invention:

Blood and immune system cells (including T cells (such as T helper cells and Tregs), B cells, monocytes, macrophages, NK cells, dendritic cells), central nervous system neurons and glial cells, contractile cells (including smooth muscle, striated muscle, skeletal muscle), keratinizing epithelial cells, wet stratified barrier epithelial cells, endothelial cells, exocrine secretory epithelial cells, hormone secreting cells, metabolism and storage cells, barrier function cells (lung, gut, exocrine glands and urogenital tract), epithelial cells lining closed internal body cavities, ciliated cells with propulsive function, extra-cellular matrix secretion cells, sensory transducer cells, autonomic neuron cells, sense organ and peripheral neuron supporting cells, lens cells, pigment cells, germ cells, nurse cells, interstitial cells.

Preferably viral replication is not affected (or is not substantially reduced) in cell types capable of stimulating an effective immune response against the wild type virus.

The virus of the invention is typically of any of the groups or species of virus mentioned herein. Preferred viruses are listed below. Positive RNA viruses

Alphaviridae, Togaviridae, Coronaviridae, Picornaviridae (e.g. polio), Caliciviridae, Astroviridae, Arteriviridae, Flaviviridae, Nodaviridae, Retroviridae (e.g. HIV).

Negative RNA viruses

Arenaviridae, Bornaviridae, Bunyaviridae, Filoviridae, Orthomyxoviridae, Paramyxoviridae, Rhabdoviridae (e.g. Lyssaviras (rabies)).

Double stranded RNA viruses

Reoviridae (e.g. Rotavirus and Blue Tongue virus), Birnaviridae

Double stranded DNA viruses

Adenoviridae, Ascoviridae, Asfarviridae (e.g African Swine Fever virus), Herpesviridae, Baculoviridae, Papillomaviridae, Polydnaviridae, Polyomaviridae, Poxviridae, Hepadnaviridae (e.g. Hepatitis viruses)

Single stranded DNA viruses

Circoviridae, Parvoviridae

Families and groups of viruses

In all cases, the virus is either an RNA or DNA virus and is optionally from one of the following families and groups: Adenoviridae; Alfamoviruses;

Bromoviridae; Alphacryptoviruses; Partitiviridae: Baculoviridae; Badnaviruses; Betacryptoviruses; Partitiviridae; Bigeminiviruses; Geminiviridae; Birnaviridae;

Bromoviruses; Bromoviridae; Bymoviruses; Potyviridae; Bunyaviridae;

Caliciviridae; Capillovirus group; Carlavirus group; Carmoviras group;

Caulimovirus group; Closterovirus group; Commelina yellow mottle virus group;

Comovirus virus group; Coronaviridae; PM2 phage group; Corcicoviridae; Cryptic virus group; Cryptovirus group; Cucumovirus virus Φ6 phage group; Cystoviridae;

Cytorhabdoviruses; Rhabdoviridae; Carnation ringspot group; Dianthovirus virus group; Broad bean wilt group; Enamoviruses; Fabavirus virus group; Fijiviruses; Reoviridae; Filoviridae; Flaviviridae; Furovirus group; Geminiviras group;

Giardiavirus group; Hepadnaviridae; Herpesviridae ; Hordeivirus virus group;

Hybrigeminiviruses; Geminiviridae; Idaeoviruses; Ilarvirus virus group ; Inoviridae;

Ipomoviruses; Iriodoviridae; Leviviridae; Lipothrixviridae; Luteovirus group; Machlomoviruses; Macluraviruses; Marafivirus virus group; Maize chlorotic dwarf virus group; Icroviridae; Monogeminiviruses: Geminiviridae; Myoviridae;

Nanavirases; Necrovirus group; Nepovirus virus group; Nodaviridae;

Nucleorhabdoviruses: Rhabdoviridae; Orthomyxoviridae; Oryzaviruses: Reoviridae;

Ourmiaviruses; Papovaviridae; Paramyxoviridae; Parsnip yellow fleck virus group; Partitiviridae; Parvoviridae including adeno- associated viruses; Pea enation mosaic virus group; Phycodnaviridae; Phytoreo viruses: Reoviridae; Picornaviridae;

Plasmarviridae; Podoviridae; Polydnaviridae; Potexvims group; Potyvirus;

Poxviridae; Reoviridae; Retroviridae; Rhabdoviridae; Rhizidiovirus group;

Rymoviruses: Potyviridae; Satellite RNAs; Satelliviruses; Sequiviruses: Sequiviridae; Sobemoviruses; Siphoviridae; Sobemovirus group; SSVI-Type Phages;

Tectirividae; Tenuiviras; Tetravirirdae ; Tobamovirus group; Tobravirus group;

Togaviridae; Tombusvirus group; Tospovimses: Bunyaviridae; Torovirus group;

Totiviridae; Tymoviruses; Tymovirus group; Plant virus satellites; Umbraviruses;

Unassigned potyviruses: Potyviridae : Unassigned rhabdo viruses: Rhabdoviridae; Varicosaviruses; Waikaviruses: Sequiviridae; Ungrouped viruses.

Modifications Made to the Virus

The virus is modified so that it has a reduced level of replication in a certain cell type of the host, leading to attenuation of the virus. The modification comprises insertion of a sequence into a location in the genome of the virus, where the inserted sequence results in a microRNA binding sequence being present that either destabilises the genome, destabilises mRNA expressed from the location or inhibits translation of protein from the genome or from mRNA expressed from the location.

Thus the inserted sequence comprises sequence which is either complementary to sequence that can act as a microRNA binding site or is the same as sequence which can act as a microRNA binding site (depending on the mechanism by which the relevant genomic sequence is expressed as mRNA). Binding of the expressed mRNA to microRNA leads to a decrease in replication of the virus.

MicroRNA binding sequences will normally be inserted into areas of the genome that are essential for virus survival or replication. This could be achieved by inserting binding sites on both sides of an essential gene/region, such as the HIV Tar element.

In the case of microRNA binding sites inserted into RNA viruses to destabilize the genome itself, insertions will normally be introduced in the 3 ' UTR and/or 5'UTR. Inclusion of sense microRNA binding sites into positive strand RNA viruses will permit destabilisation of the virus genome and prevention of direct translation. Should the virus replication proceed to the production of negative strand copies, inclusion of microRNA binding sites within the negative strand (which were encoded as 'antisense' sequences in the positive strand) will then act to destabilise the negative copies of the genome. In negative stranded RNA viruses the inclusion of a 'sense' microRNA binding site within the negative strand of the genome will act to destabilise it, and inclusion of an 'antisense' version within the negative strand will destabilise positive strand copies and also prevent their translation.

Also insertions maybe made in order to disrupt coding regions of unwanted proteins. All of these insertions will act to destabilize the genome itself and any sub- genomic RNA also produced from said genome.

Typically at least 1, 2, 3, 4, 5 or more, for example up to 10, 20 or 30 microRNA binding sites are inserted into the genome of the virus. The binding sites which are inserted may have the same sequences or may have different sequences. They may bind the same microRNA sequence or may bind different microRNA sequences. Each insertion may comprise at least 1, 2, 3, 4, 5 or more, for example up to 10 binding sites.

The binding sites may be inserted in any suitable location, but are preferably inserted in the 5' or 3' un-translated region of the virus genome or of a virus gene, typically within 300, or preferably 200 or more preferably 100 nucleotides of coding sequence. They may be inserted into a coding sequence of a viral gene. The relevant gene is typically an essential gene or a gene that when absent provides an increased immune response. A preferred gene is nef protein in HIV; another preferred gene is Vpr or Vpu in HIV.

A typical insertion would include more than 1 binding site. Four or more repeats of the binding sites are preferred. The sequence below shows an insertion that contains 4 binding sites to mir-150 separated by a few bases (randomly chosen).

5 ' ctagaagagggttgggaacatggtcacatatatagagggttgggaacatggtcacgggggggagagggttggg aacatggtcacatatatagagggttgggaacatggtcacgc 3'

The sequence is flanked by restriction enzyme overhangs, in this case Xbal (ctaga) and Notl (gc). This is obviously different for each insertion.

Preferred positions for the binding sites are regions of the viral genome that are exposed to interaction with cytoplasmic proteins, including regions of the 3' and

5' UTRs that have an extended secondary and tertiary structure, allowing good access to binding proteins. The binding sequence may be capable of binding the relevant microRNA sequence, and thus is generally (i) complementary to the relevant microRNA sequence or (ii) homologous to a sequence which is complementary to the microRNA sequence. Thus the binding sequence may be a portion of a naturally occurring microRNA binding sequence or all or a portion of a homologue of a naturally occurring microRNA binding sequence. Typically the binding sequence is at least 15 nucleotides long and/or has at least 70% homology to the microRNA sequence.

In one embodiment binding sites are inserted in at least one location, preferably two where the two locations flank an essential region/gene of the virus. Typically such locations may be between 200 and 200,000 nucleotides apart, more preferably between 200 and 12,000 nucleotides apart and more preferably between

200 and 5000 nucleotides apart .

In the case of microRNA binding sites inserted into RNA or DNA viruses to destabilize viral mRNA required for replication, insertions will normally be in the 3 ' and/or 5 ' UTR of the individual gene transcripts, including within the UTRs of poly- cistronic mRNA transcripts. Examples of viral gene transcripts to be destabilized include Adenovirus ElA mRNA, EBV EBNA-I mRNA, HSV-ICP34.5 mRNA, HIV-Nef mRNA, HIV-Vpr niRNA, HIV- Vpu mRNA, HIV- Vif mRNA, SV40-large T antigen mRNA, Vaccinia - Thymidine Kinase mRNA transcripts. In addition, the virus of the invention may or may not have other genetic modifications, such as other modifications which make the virus safer to use as a vaccine and/or contribute to attenuation of the virus. Typically the virus may have modified sequence or may comprise deletion of sequence. The virus of the invention may or may not carry additional nucleotide sequence, such as heterologous (e.g. non- viral sequences other than the microRNA binding sites) sequence.

The virus may in addition have non-genetic modifications, for example the virus may be sterically stabilised by surface coating with reactive hydrophilic polymers. As mentioned above, in one embodiment the virus may be killed.

MicroRNA sequences

Mature microRNA sequences are freely available through the database miRbase at http ://microrna. sanger.ac.uk/. This database contains all current microRNA sequences in all organisms and allows easy navigation between species and different microRNA molecules. The current, and most up to date, database version is 11.0 and the data within this database is incorporated herein by reference. The miRBase Sequence database, and its use, is described in the following articles:

miRBase: tools for microRNA genomics. Griffiths- Jones S, Saini HK, van Dongen S, Enright AJ. Nucleic Acids Res. 2008 36:D154-D158

miRBase: microRNA sequences, targets and gene nomenclature. Griffiths- Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. Nucleic Acids Res. 2006 34:D140-D144

The miRNA Registry. Griffiths- Jones S. Nucleic Acids Res. 2004 32:D109-

Dl Il MicroRNA tissue specificity

The niicroRNA molecules which are bound by the binding sequences present in mRNA expressed from the virus are expressed by at least one cell type of the host. This is usually a cell which is infected by the wild-type form of the virus in natural infection. Typically the relevant microRNA molecules have tissue-specific expression, or preferably tissue-specific "non-expression", i.e. are not expressed in certain cells of the host. Zhou et al (2007) PNAS 104, 7080-85 and Landgraf et al (2007) Cell 129, 1401-14 contain disclosure which is relevant to the present application, and are incorporated herein by reference, hi particular the microRNA sequences disclosed in those papers and information relating to their tissue specificity is incorporated herein by reference.

Preferably the virus is capable of replicating in at least one cell type in which the microRNA is not expressed (but as discussed above whilst such replication should preferably stimulate an immune response to the virus, it should not result in disease of normal severity).

In embodiments where the virus is able to bind more than one type of microRNA, virus replication would be inhibited in any cell which expressed any of the microRNAs for which the virus had a binding site. This could be used to further restrict the cell types in which the virus could replicate, allowing viruses to be made which replicated in fewer cell types.

The microRNAs that are bound could be highly conserved (for example identical) between species (for example between mouse and man). The microRNAs would typically be of length 15 to 30 nucleotides, for example 20 to 25 or 21 to 23 nucleotides. The microRNAs could be the same as or homologous to any of the specific microRNA sequences mentioned herein.

Binding of a microRNA to the a binding site is illustrated below: i.e. Mir- 150 mature sequence is 5' ucucccaacccuuguaccagug 3'

The binding site would then be the opposite 3' agagggttgggaacatggtcac 5' Or (same binding sequence in reverse) 5 ' cactggtacaagggttgggaga 3 ' Additionally, many microRNA molecules do not exhibit tissue specificity and some vaccines according to the invention may require suppression of viral replication and/or gene expression in all cell types infected. Therefore, rather than incorporating binding sites to microRNA molecules that demonstrate tissue specific expression it may be necessary to incorporate binding sites to microRNAs that are ubiquitously expressed. Moreover, some of the microRNA molecules that demonstrate the highest levels of cellular expression are expressed ubiquitously and are therefore extremely suitable for preventing viral replication in the use of the invention.

Homology

Homologues of sequences are referred to herein. Such homologues typically have at least 70% homology, preferably at least 80, 90%, 95%, 97% or 99% homology, for example over a region of at least 15 or at least 20 contiguous nucleotides, or over the entire length of the relevant homologue sequence. The homology may be calculated on the basis of nucleotide identity (sometimes referred to as "hard homology").

For example the UWGCG Package provides the BESTFIT program which can be used to calculate homology (for example used on its default settings)

(Devereux et al (1984) Nucleic Acids Research 12, p387-395). The PILEUP and BLAST algorithms can be used to calculate homology or line up sequences (such as identifying equivalent or corresponding sequences (typically on their default settings), for example as described in Altschul S. F. (1993) J MoI Evol 36:290-300; Altschul, S, F et al (1990) J MoI Biol 215:403-10.

Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (http://www.ncbi.nhn.nih.gov/). This algorithm involves first identifying high scoring sequence pair (HSPs) by identifying short words of length W in the query sequence that either match or satisfy some positive- valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighbourhood word score threshold (Altschul et al, supra). These initial neighbourhood word hits act as seeds for initiating searches to find HSPs containing them. The word hits are extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Extensions for the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T and X determine the sensitivity and speed of the alignment. The BLAST program uses as defaults a word length (W) of 11, the BLOSUM62 scoring matrix (see Henikoff and Henikoff (1992) Proc. Natl. Acad. ScL USA 89: 10915-10919) alignments (B) of 50, expectation (E) of 10, M=5, N=4, and a comparison of both strands.

The BLAST algorithm performs a statistical analysis of the similarity between two sequences; see e.g., Karlin and Altschul (1993) Proc. Natl. Acad. ScL USA 90: 5873-5787. One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two polynucleotide or amino acid sequences would occur by chance. For example, a sequence is considered similar to another sequence if the smallest sum probability in comparison of the first sequence to the second sequence is less than about 1, preferably less than about 0.1, more preferably less than about 0.01, and most preferably less than about 0.001.

The homologous sequence typically comprises less than 10, less than 6 or less than 4 mutations (which may be substitutions, deletions or insertions of nucleotides). These mutations may be measured across any of the regions mentioned above in relation to calculating homology

Production of Viruses

To generate attenuated viruses containing microRNA sequences general molecular cloning techniques will be employed. RNA viruses will typically be engineered in cDNA form in standard plasmid vector backbones (for example, pUC19, pUC18). DNA viruses will be engineered in DNA form using standard plasmid vector backbones (for example, pUC19, pUC18). Large DNA or RNA viruses (for example, Coronaviruses, Asfarviridae, Poxviridae, Herpesviridae) may be engineered using bacterial artificial chromosome backbones (BAC), Yeast artificial chromosome backbones (YAC), cosmid backbones or Pl -derived backbones (PAC). Following identification of a sequence site for microRNA insertion, (e.g 5' UTR, 3' UTR) unique restriction sites will be identified using programs such as Pdraw or Laser gene or vector NTI. Unique restriction sites may be created by either reducing vector size to eliminate undesirable restriction sites or by assembly PCR to introduce unique restriction sites. Regions of viral genomes may also be extracted using flanking restriction sites and ligated into standard plasmid vector backbones to produce unique sites within the flanked region. Introduction of microRNA binding sequences can be achieved by either sequential PCR steps or annealed oligo ligation. To perform annealed oligo ligation, oligos are generated by phosphoamidite chemistry and can be purchased from Sigma Aldrich. The design of sense oligos includes the complementary coding sequence of the microRNA which will repress the viral replication in a specific cell lineage or type. This sequence can either be in the 5' to 3' orientation or the 3' to 5' orientation. Alternatively, microRNA binding sites will also be introduced into RNA viruses such that they will only be bound by said microRNA in the anti-sense strand of the virus's normal genome. Termed herein 'anti-sense microRNA binding sites'. Typically generated oligos will contain 1, 2, 3, 4 or more complementary microRNA binding sites, preferably 2, 3 or 4. These binding sequences are separated by 5-50 base pairs. This region may include unique restriction sites or viral elements such as packaging signals. Restriction digest overhangs will also be added to the 5' and 3' ends of the oligo 's to allow ligation to occur. An oligo complementary to the aforementioned oligo is also generated minus the necessary overhangs required for ligation into identified unique sites within the viral genome.

Complementary oligos are annealed in either TE, water, restriction digest buffer or annealing buffer (10OmM potassium acetate, 3OmM HEPES (pH7.4), 2mM magnesium acetate). Oligos are heated to 100-95⁰C for 5 minutes and then cooled to 4°C over a time period of between 5 minutes to 24 hours. Ligations are performed using DNA ligase and using standard protocols at either room temperature for 1-2 hours, 10⁰C to 16°C overnight or 4°C for over 24 hours. Ligations are performed with a molar excess of oligos to vector usually at ratio of 3:1 and not usually exceeding 50:1.

DNA ligations are transformed into chemically competent or electro- competent cells using standard protocols and plated using vector backbone specific selection media (e.g Ampicillin (lOOug/mi), Kanamycin (50ug/ml)). Vectors are screened for oligo insertion using standard restriction digest methods. To insert more binding sites than can be achieved by a single annealed oligo ligation, multiple oligos sharing homology at one of each of their termini allows multiple oligo ligations which can insert larger numbers of microRNA binding sites (See diagram below).

Annealed oligo Annealed oligo Vector backbone pair pair

"T¹I¹¹¹I ' ϊ l^*π~rriTTTTTl~π^*T^* i i i i i i i i i i i i i i i i i i i i i i i i i ι T~ i i I I I I I I I I I I I I I I I I I DNA

Unique vector Region of Unique vector restriction oligo restriction overhangs homology overhangs

MicroRNA binding sites may also be incorporated into viral genomes using sequential PCR steps using primers which contain complete or partial microRNA binding sites at their 5' ends. Following the initial PCR using these primers, further primers which are specific for the 5' sequence added by the previous primers are used to amplify further. These primers in turn have more partial or complete microRNA binding sites at their 5' end. Following multiple rounds of amplification using unique sequences to anneal primers to, multiple microRNA binding sites could be added into a vector. The final primers used for ligation contain unique restriction sites which allow vector re-ligation. Viruses are grown and produced in cells suitable for viral replication and viruses are purified and analysed using methods specific for each virus.

Use of suicide enzymes to prevent unwanted pathology

The invention may also be used in conjunction with a suicide gene and prodrug system in which the virus may be cleared at any point following the vaccine administration. The virus would express the suicide gene which is inserted into the viral genome, producing an enzyme capable of activating an innocuous pro-drug to produce a cytotoxic species. The activated prodrug will kill the infected cell. Inclusion of such a suicide gene would allow increased safety of the vaccine by allowing infection to be cleared to prevent any potential disease pathology. Suitable enzymes that could act as suicide genes include Nitroreductase, Herpes Simplex Thymidine Kinase and Cytosine Deaminase used in conjunction with CB1954 (5- [Aziridin-l-yl]-2.4dinitrobenzamide), Acyclovir/Gancyclovir and 5-flurocytosine respectively. Nitroreductase may also reduce any quinone or nitroaromatic substance delivered as a pro-drug. In some manifestations of the invention transcription of the suicide gene will be controlled by inducible promoters, for example by using a Tet on system. In other manifestations of the invention transcription of the suicide gene will be controlled by tissue specific promoters, for example to provide expression and control if the virus should become active in sites of potential toxicity.

Therapeutic uses

Viruses of the invention may be used in methods of therapy in the treatment of disorders. The virus is typically administered into a single site, or into two or more sites for example by intradermal, subcutaneous (including using ballistic devices), intravenous, intraperitoneal, intramuscular injection, topically onto external or mucosal surfaces, by suppository or other indwelling implant. The amount of virus administered is typically in the range of from 10⁴ to 10¹⁰ pfu, preferably from 10⁵ to 10⁸ pfu, more preferably about 10⁶ to 10⁸ pfu depending on the specific virus applied. When injected, typically from 1-200 μl preferably from 1 to 10 μl of virus suspension, depending on the species, in a pharmaceutically acceptable suitable carrier or diluent, is administered.

The routes of administration and dosages described are intended only as a guide since a skilled practitioner will be able to determine readily the optimum route of administration and dosage. The dose of a modulator may be determined according to various parameters, especially according to the substance used; the age, weight and condition of the patient to be treated; the route of administration; and the required regiment. A physician will be able to determine the required dosage for any particular patient.

Examples of Specific microRNA/virus combinations

1. Prevention of Human Immuno-Deficiency virus (HIV) from replicating in CD4+ T cells. 2. Prevention of Human T-Lymphotropic viruses I, II, III and IV replication and gene expression in T lymphocytes.

3. Prevention of Avian Leukosis virus replication in B cell populations

4. Prevention of Bovine Leukaemia virus replication in B cell populations. 5. Attenuation of Rhabdoviruses by preventing neural replication (Including

Rabies (lyassa virus), Chandipura virus and vesicular stomatitis virus (VSV))

6. Attenuation of Hepatitis D virus in hepatocytes.

7. Further attenuation of the live Sabin Polio vaccine by preventing neural replication. 8. Attenuation of Hepatitis C, E, F and G viruses in hepatocytes.

9. Attenuation of Alphaviruses in neural tissue, macrophages and skeletal muscle.

10. Attenuation of Dengue virus in cells of the monocytes/macrophage lineage.

11. Attenuation of Coronavirases in gut and lung epithelium 12. Attenuation of Blue Tongue virus and Human rotavirus replication

13. Attenuation of Influenza virus in upper and lower lung epithelium.

14. Attenuation of Kaposi's Sarcoma-associated virus (KSHV) and Epstein-Barr virus (EBV) to prevent latency and replication in B cells.

15. Attenuation of African Swine Fever virus in cells of the monocyte and macrophage lineage.

16. Attenuation of Hepatitis B virus in Hepatocytes.

Preferred virus/microRNA combinations

17. Attenuation of Marek's disease virus in B cells by incorporating microRNA binding sites to one, or more, of the following microRNA molecules mirl42, mir-150, mir-155 and mir-146. Transcripts targeted for microRNA mediated suppression or degradation will be essential for replication or disease pathology.

18. Attenuation of Alphaherpesviridae (including Pseudorabies) virus in neural tissue.

19. Attenuation of West Nile Fever virus in hepatocytes and neurons. Other Preferred Viruses and Disease Targets

Vaccinia - (encoding Cardiac microRNA binding sites for cardiac protection) Cocksackie virus - (encoding Cardiac microRNA binding sites for cardiac protection) Pestiviruses - (Classical Swine fever and bovine viral diarrhoea)

Picornavirus - (enterovirus, rhinovirus, hepatovirus, cardiovirus, aphthovirus) Arteriviruses - (Equine Arteritis virus, Porcine reproductive and respiratory syndrome virus, Lactate dehydrogenase elevating virus simian heamorrhagic virus) Coronaviruses - (Severe Acute Respiratory Syndrome virus) Paramyxovirus - (Hendra virus, Nipah virus) Orthomyxovirus - Avian Influenza Porcine Circoviruses Malignant catarrh virus Adenoviridae — Mastadenovirus — Human, Canine, Equine Adenoviruses. Suppression in hepatocyte/Respiratory infections and gastrointestinal infections hi general control of virus replication in the above examples will be achieved by the incorporation of multiple microRNA binding sites in any given location within the viral genome to mediate either genome instability, direct prevention of viral genome translation and replication or preventing expression of mRNA transcripts essential for virion replication, hi RNA viruses binding sites can be inserted in either the sense or anti-sense orientation to mediate effective repression of both positive and negative genomic strands during their replication cycle.

Applicability to retroviruses (positive stranded RNA viruses replicating through a DNA intermediate) focusing on HIV

HIV suppression using endogenous microRNAs expressed in CD4+ T cells.

The humoral and cell mediated immune response triggered by a viral infection are dependent entirely on one group of cells, the CD4+ T helper cells.

These cells function as positive regulators and the help they provide is essential for the activation of all T and B lymphocytes by their cognate receptors. Consequently, without them, no lasting or significant immune response can be mounted against pathogens.

Human immunodeficiency virus (HIV) is an enveloped lentivirus containing two identical copies of a positive sense RNA genome approximately 9kb in length. Viral entry is mediated by the gpl20 glycoprotein that allows CD4+ mediated endocytosis. HIV is phylogenetically highly variable and consequently some isolates preferentially infect macrophages and T lymphocytes. Such isolates are called M tropic or R5 and T tropic or X4 respectively. Initial infection of an individual is by the M tropic (R5) strain which can efficiently infect both macrophages and CD4+ T cells. However, following acute infection (2-4 weeks) and a decrease in viremia, selection of a T cell specific virus emerges. This is probably a consequence of the high abundance of T cells in the lymphoid tissues in which the virus efficiently replicates. In spite of T cells being the major site of viral replication, production of virus from macrophages has been shown to continue throughout the course of infection and may serve as a reservoir of virus following CD4+ T cell depletion which abrogates the onset of acquired immuno-deficiency syndrome (AIDS). Theoretically, if T cells could not be infected the virus would be under no selective pressure to form the X4 strain.

During HIV infection the CD4+ cells affected include mature macrophages, activated CD4+ T cells, dentritic cells, monocytes (undifferentiated macrophages in the circulation) and microglia. Resting T cells are unsusceptible to infection due to low concentrations of nucleotides required for reverse transcription. The infection of microglial cells has been linked with latency due to low levels of cell mediated immune surveillance in those sites. Dentritic cells have been shown to be responsible for virus transit from the mucosal surface to the lymph node which leads to infection of CD4+ T cells; however, replication also occurs in these cells at a lower frequency. The main cause of acquired immuno-deficiency syndrome (AIDS) is believed to be declining CD4+ T cells to below 200 cells/μl which leads to complete loss of cell mediated immunity. HIV replication has previously been shown to be successfully prevented by

RNA silencing using RNA interference. Unfortunately, this technique relies on delivering siRNA to specific target cells in order to induce viral mRNA degradation, a treatment that is currently unfeasible. Furthermore, the use of siRNAs to target HIV genomic regions results in only a single target site for siRNA mediated RNA degradation. If this single site is mutated virus escape will occur.

However, cellular encoded microRNAs can be used in a similar strategy to prevent HIV replication. By incorporating binding sites into the HIV genome for any microRNA which is expressed in mature or activated T cells it is possible to prevent viral gene expression in those cells and possibly decrease integration by targeting the incoming, unpackaged genome. Mature T cells and B cells highly express a microRNA termed mir-150 which can be used to prevent mature T cell HIV replication. The Thymus expresses a microRNA termed mir-181 and HIV infection has been shown to limit T cell hematopoiesis from the Thymus. Therefore, this microRNA may help to maintain T cell production.

The above will be achieved by generating three recombinant viruses containing four, eight and twelve microRNA binding sites throughout the genome of HIV (Four binding sites in three locations). Whilst four of these binding sites will be contained within the 3' UTR of the viral genome, i.e. the most common region for microRNA binding sites to be found naturally, a 5 ' UTR and an internal insertion will also be made. These insertions would also be found in any mRNA produced from any integrated HIV genome. The prevention of integration may also be possible because the viral genome consists of two identical capped and poly- adenylated mRNA molecules and would, if presented to microRNA machinery, be subject to repression or degradation and prevent reverse transcription.

This mechanism of suppression will not prevent viral infection in macrophages, dentritic cells and microglia. These cells will support replication and allow virus antigen presentation and the release of virions to induce the production of neutralising antibodies by B cells and the establishment cytotoxic T lymphocytes to HIV infected cells whilst maintaining cell mediated immunity. Critically, T helper cells population will be preserved which will allow T and B cell activation. Currently, the proliferation of T cells is advantageous to HIV replication, however, if T cells are now un-susceptible to viral infection, proliferation will continue until the clearance of infected cells is complete. Cells in which HIV becomes latent should become destroyed at later time points should the virus re-activate. As previously discussed microglia and dendritic cells can be infected, however, dendritic specific and microglial specific microRNA molecules could also be utilised to prevent viral replication in those cell types. Brown et al have previously shown that transgene expression can be silenced in dentritic cells using this mechanism with binding sites to mir-155. Glial and microglial cells have also been shown to express mir-124 and could therefore be protected in a similar mechanism. This would result in a macrophage specific replication competent HIV that could be efficiently cleared from the circulation by both B and T cells and would result in a large memory pool of both cells. Moreover, virus replication could be further limited by incorporating microRNA binding sites recognised by microRNA molecules expressed in macrophages. These include Mir-142, mir-155, mir-15a, mir-29a, mir-21, mir-23a. MicroRNA molecules disclosed herein are offered as example microRNA molecules and are not an exhaustive list. Binding sites to any microRNA expressed in cells infected by the virus could be used to repress viral gene expression or replication.

The viral strain originally selected could be of either the M tropic (R5) or T tropic (X4) categories, however, the use of an M tropic isolate will further limit T cell viral replication should it be required. This also has the benefit of priming the immune system using the form of the virus most likely to be encountered on initial infection. Moreover, to further attenuate the virus, important deletions can be made to limit the viruses function in T cells. These include the deletion, or inactivation by insertion, of the nef protein and/or the deletion of the vpr protein. These will become insertion sites for microRNA binding sites. Infected individuals with nef- HIV typically have a far slower onset of disease due to slower infection and destruction of T cell populations. Moreover, Nef protein has been implicated in the down- regulation of MHC Class- 1 protein presentation on the surface of infected cells and therefore its deletion will allow more efficient antigen presentation. Consequently, this deletion would act to further attenuate the vaccine and enhance the immune response. Furthermore, Simian Immuno-deficiency virus (SIV) trials using Nef deleted strains have shown to be highly effective as live vaccines, however, CD4+ T cell numbers still declined in some test animals which has prevented further investigation into this strategy. The coding region of the vpr protein lies within the central region of the HIV genome and is therefore a suitable insertion site for microRNA binding sites given the decreased possibility of a central and terminal deletion. Vpr protein accelerates viral replication and cytopathic effects in T cells and the vpr protein is found within viral the capsid and may help to initiate the early infection cycle. Therefore, deletion of this non-essential gene should cause slower viral replication and further desirable attenuation. Viruses will also be made in which deletions are not made but still contain said binding sites.

Reversion is a major issue for any virus which utilises a low fidelity RNA dependent or DNA dependent RNA polymerase during its replication cycle. HTV reverse transcriptase similarly shows high mutability and may increase the incidence of vaccine induced disease. Previous data has shown that polio virus acute infection is dependent on the low fidelity of its viral RNA dependent RNA polymerase and the incorporation of a high fidelity RNA polymerase prevents acute infection. Consequently, mutations which allow the production of a high fidelity reverse transcriptase in HIV would lower the reversion rate of any microRNA suppressed vaccine. Previous work on HIV-I RT has shown that the substitution of Valine 148 to a number of uncharged amino acids, including Isoleucine, results in high-fidelity. The negative affects of this mutation is a reduction in the epitope variability presented to the immune system during vaccination. Similarly, a high fidelity reverse transcriptase could be produced by fusing the 3' to 5' exonuclease regions of DNA polymerase enzymes to reverse transcriptase. This would allow proofreading activity to be produced.

The prevention of HIV integration may be further enhanced by decreasing the efficiency of reverse transcription. Decreased processivity of reverse transcription demonstrating 11% loss of fitness has been shown to be caused by a Leucine to valine at residue 74 which is induced by didanosine (ddl) treatment. Another mutation showing the same properties is methionine to valine at residue 184 of reverse transcriptase which is induced by 3TC treatment. To maintain these mutation vaccines may be administered with either 3TC or didanosine.

The insertion of HIV into the host genome allows the virus to maintain gene expression continuously for the life of an infected cell. This results in an infection which is more difficult to clear than the infection of a virus which does not integrate. Gene delivery vectors have been generated based on retroviral/lentiviral backbones that do not integrate into the host genome. These vectors, whilst exhibiting some long term gene expression, do not continue to express genes for the life of the cell and cannot be maintained during cell division (for example, during T cell clonal expansion in response to antigen). Therefore, the use of a non-integrating replication competent HIV vector in conjunction with the invention would prevent long term latency in cells not initially cleared by the immune system. Such a non-integrating replication competent virus has not yet been generated as a vaccine and is therefore both novel and untested, and could be improved through tissue selectivity introduced by the application of this invention.

The induction of cell mediated immunity using a variety of viruses expressing HIV epitopes has so far proven ineffective at preventing HIV infection; moreover, none have produced long term CTL responses in individuals capable of preventing infection. Future clinical trials involving such techniques are therefore unlikely to succeed. The percentage of infected individuals in some HIV prevalent populations now exceeds 50% and the use of a safe cost-effective replication competent vaccine is likely to be the only answer to halting the HIV epidemic.

Human T-Lymphotropic viruses I, II, III, IV

Human T-Lymphotropic viruses I, II, III, TV are all positive stranded RNA retroviruses that have been linked with T-cell leukaemia, T-cell lymphoma and demyelinating disease. These viruses replicate in T cell populations and HTLV-I has been shown to have an immuno-stimulatory function on a subset of T-helper cells (ThI) which causes a decrease in the function and activity of Th2 cells. This results in decreased immune surveillance by the latter cells which can lead to opportunistic infection. Therefore, preventing or reducing viral replication in T cells, possibly in conjunction with deletions of oncogenic genomic regions would result in an effective live vaccine. This could be achieved by inserting microRNA binding sites to one or more of the following microRNA molecules: Mirl50, Mir-155, Mir- 146, Mir-15a and Mirl42. These microRNA molecules are offered as example microRNA molecules and are not an exhaustive list. Binding sites to any microRNA expressed in cells infected by the virus could be used to repress viral gene expression or replication.

Suitable insertion sites include the 3'UTR of all Gag, Pol and Env genes which are all located at the last 1000 bp (3' end) of the viral genome. Insertions may also be made in the 5 ' UTR of the aforementioned genes which is within the last lOOObp (5' end) of the viral genome. MicroRNA insertions could also be made to disrupt any oncogenic regions within the viral genome and also between the Env and Tax transcripts of HTLV-I and II. These insertions may either prevent gene expression from an inserted vector or may destabilise the viral genome following un- packing or un-coating within the host cell prior to integration.

Avian Leukosis virus

Avian Leukosis virus (ALV) is a member of the retrovirus family and consequently contains a positive stranded RNA genome that replicates through a DNA intermediate inserted into the host genome. ALV causes the poultry disease lymphoid leukosis and is mainly managed by eradication of infected birds from poultry flocks. Replication and integration of the virus occurs in B cell populations and therefore prevention or a reduction in replication in those cell types would be an effective live recombinant vaccine. This could be achieved by inserting microRNA binding sites to one or more of the following microRNA molecules mir-142, mir- 15a, mir-150, mir-155 and mir-146. These microRNA molecules are offered as example microRNA molecules and are not an exhaustive list. Binding sites to any microRNA expressed in cells infected by the virus could be used to repress viral gene expression or replication. Suitable insertion sites include the 3'UTR of all Gag, Pol and Env genes which are all located at the last 1000 bp (3' end) of the viral genome. Insertions may also be made in the 5' UTR of the aforementioned genes which is within the last lOOObp (5' end) of the viral genome. These insertions may either prevent gene expression from an inserted vector or may destabilise the viral genome following un- packing or un-coating within the host cell prior to integration. Bovine Leukaemia Virus

Enzootic Bovine Leukosis is a disease of cattle caused by the retrovirus bovine leukaemia virus (BLV). Most infections with this virus are sub-clinical, however, approximately 30% of cases develop into lymphocytosis with some of these cases progressing to the formation of lymphosarcomas on multiple internal organs. Infection has also been observed in sheep and buffaloes and the invention herein described is applicable to those animals also. There is currently no vaccine available for BLV. The major target sites for infection are lymphocytes of the B cell lineage. This could be achieved by inserting microRNA binding sites to one or more of the following microRNA molecules mir-142, mir-15a mir-150, mir-155 and mir- ^■146. These microRNA molecules are offered as example microRNA molecules and are not an exhaustive list. Binding sites to any microRNA expressed in cells infected by the virus could be used to repress viral gene expression or replication. Suitable insertion sites include the 3'UTR of all Gag, Pol and Env genes which are all located at the last 1000 bp (3' end) of the viral genome. Insertions may also be made in the 5' UTR of the aforementioned genes which is within the last lOOObp (5' end) of the viral genome. These insertions may either prevent gene expression from an inserted vector or may destabilise the viral genome following un-packing or un-coating within the host cell prior to integration.

Applicability to single negative stranded RNA viruses focusing on Rhabdoviruses (Including Rabies (Lvassa virus), Chandipura virus, vesicular stomatitis virus (VSV) and Hepatitis D virus. ^•

Negative stranded RNA viruses replicate using a RNA dependent RNA polymerase transported in the viral capsid from the cell of origin. This polymerase mediates positive sense genomic strand production from which viral genes are translated and new negative strand genomic synthesis occurs.

Rabies virus is a negative stranded RNA virus belonging to the family Rhabdoviridae and infects a variety of animals and also humans. Almost all un- vaccinated individuals who contract rabies virus, and receive no treatment, die as a result of encephalitis. Current pre-exposure vaccination strategies include the use of live-attenuated virus in wild animal populations and pets and the use of killed vaccine in humans. Human vaccinations are limited to those likely to contact infected animals for example those travelling to, or living in, regions in which the disease in prevalent and also veterinary staff. Rabies is prevalent in Latin America, Asia and Africa with India alone reporting approximately 25000 human cases per year. Despite good vaccine availability long lasting immunity is not established using the dead vaccine and all individuals who are bitten by an infected animal must receive post-exposure prophylaxis.

The time period prior to the onset of disease in a Rabies infected individual can vary greatly and may be due to replication at the site of initial infection and the distance the virus must travel along neurons to access the brain. Rabies virus often replicates at the site of initial infection in muscle cells whilst causing no clinical signs of infection. Disease is solely associated with neural replication. Therefore, to accurately mimic Rabies infection by vaccination muscular replication without neuro-invasiveness must be achieved. By incorporating microRNA binding sites for neuron specific microRNAs into the Rabies genome, replication and consequently disease can be prevented. Binding sites for a neuron specific microRNA could be incorporated in the sense direction in the negative strand of the genome. Binding sites for different neuron specific microRNA, to prevent complimentary binding to the aforementioned binding sites, could be incorporated in the sense orientation in the positive strand of the genome. This would result in a virus in which both the negative and positive copies of the genome would be subject to suppression and/or degradation. If the virus mutated one set of binding sites the other set must also be mutated on the complimentary strand to allow neural replication. This would effectively make the virus twice as safe compared to a single microRNA binding site insertion.

MicroRNAs capable of preventing neural replication include mir-124, mir- 128, mir-125 and mir-26. These microRNA molecules are offered as example microRNA molecules and are not an exhaustive list. Binding sites to any microRNA expressed in cells infected by the virus could be used to repress viral gene expression or replication. Hepatitis D

Hepatitis D (Delta) virus (HDV) is dependent on the replication of Hepatitis B virus in order to replicate itself and is therefore often referred to as a subviral satellite. HDV infection is known to increase the chances of developing liver cirrhosis and hepatocellular carcinoma. The genome of the virus is negative stranded RNA in a covalently closed circle approximately 1.7Kb in length. The HDV genome is unique among sub-viral satellites in that it encodes for two proteins from a single open reading frame called the small and large delta antigens. Replication of viral genome is believed to be dependent on host polymerases. The incorporation of microRNA binding sites to a hepatocyte/liver specific microRNA such as mir- 122/mir-122a would prevent or decrease delta antigen expression and viral replication by destabilising the genome itself. Suitable insertion sites include the 3' or 5' UTR of the HDV genome.

Applicability to RNA positive stranded viruses focusing on Polio virus

Increased safety of Polio virus vaccine using endogenous microRNAs expressed in neuronal cells.

Polio virus is a member of the picornaviridae and contains an RNA genome approximately 7.5Kb in size. Widespread vaccinations to Polio using a live replication competent virus, containing multiple nucleotide substitutions was successful in dramatically reducing the number of cases of poliomyelitis. This vaccine has the ability to replicate effectively in the gut of vaccinated individuals but is unable to infect and replicate within neurons. This property is caused by a single base pair substitution within the internal ribosome entry site (IRES) in the 5' UTR of the viral genome.

The ability of the virus to replicate without causing disease is integral to the success of this vaccine. The estimated reversion rate is approximately 1 in 10⁶ administered doses. This level of reversion was considered acceptable when infection of Polio virus was widespread in the developed world. However, the United States has adopted to immunise using a killed Polio vaccine due to the increased safety despite the cost of live and dead vaccines being 7 cents and 3$ respectively. The replication of this virus is dependent on the use of a virally encoded RNA dependent RNA polymerase. This enzyme is highly error prone and therefore the rate of reversion is surprisingly low. In vitro data suggests an error rate for incorrect base insertion at between 3.2 x 10⁵ and 4.3 x 10⁷. HIV reverse transcriptase has an error rate of approximately 3 x 10⁵.

To enhance the safety of the existing Sabin Polio vaccine strain, binding sites to neuron specific microRNAs could be incorporated in the sense orientation in both the negative and positive strands of the genome (see Rabies virus attenuation) to further prevent acute neuronal infection. The viral genome could therefore be silenced and destroyed upon infection of neuronal cells whilst still retaining replication competence in gut epithelium.

Potential microRNAs for which binding sites could be incorporated are mir- 124, mir-128, mir-125 and mir-26 which have all previously been demonstrated to be highly neuron specific. These microRNA molecules are offered as example microRNA molecules and are not an exhaustive list. Binding sites to any microRNA expressed in cells infected by the virus could be used to repress viral gene expression or replication.

Hepatitis C, E, F and G These viruses are all positive stranded RNA viruses that infect and replicate within hepatocytes. By incorporating microRNA binding sites to liver specific microRNA molecules, for example mir-122a/mir-122, this cycle of replication can be reduced or prevented. In the absence of any other site of replication these vaccines would be designed as low or non-replicating; however, if another site of replication be established they would be used as live vaccines.

Currently, the study and growth of these viruses is limited with no tissue culture model available. Therefore, efficient delivery of these vaccines may depend on non- viral delivery systems for viral genome delivery and infection initiation. Alphaviruses including Sindbis virus, Semliki Forest Virus, O 'nyong 'nvons virus, Chikungunya virus. Mayaro virus, Ross River virus Eastern Equine encephalitis virus, Western encephalitis virus and Venezuelan equine encephalitis virus.

Alphaviruses contain positive sense RNA genomes between 11 and 12 Kb in length. They all contain two open reading frames transcribed from two separate RNA molecules, the foil-length genome and a sub-genomic RNA molecule. During infection they typically exhibit neuro-invasiveness and replication and may also infect skeletal muscle and macrophages. MicroRNA binding sites to skeletal muscle, macrophages and neurons would prevent viral replication in these tissues and allow efficient vaccination. The binding sites would be incorporated into the 3 ' UTR and/ or the 5' UTR of the genomic RNA in either sense or anti-sense orientation.

Neural microRNA molecules for which binding sites could be used include mir-124, mir-128, mir-125 and mir-26. MicroRNAs specific to skeletal muscle that could prevent replication include mir-206, mir-1 and mir-133. MicroRNAs specific to macrophages include mir-142, mir-155, mir-15a, mir-29a, mir-21, mir-23a. These microRNA molecules are offered as example microRNA molecules and are not an exhaustive list. Binding sites to any microRNA expressed in cells infected by the virus could be used to repress viral gene expression or replication.

Dengue virus

Dengue virus (DV) is a blood borne pathogen transmitted by mosquitoes and can be classified into four main serotypes (1-4). The serotypes are closely related and antigenically very similar. Infection with one serotype provides life long resistance to infection by that serotype but unfortunately only offers partial or transient protection to other serotypes. DV is endemic in over 100 countries and can, in severe cases, causes Dengue haemorrhagic fever (DHF) or Dengue shock syndrome (DSS). Approximately two fifths of the world's population (2500 million) are at risk to DV infection with an estimated 50 million infections annually.

DV has a single stranded positive sense RNA genome and primarily infects and replicates in cells of the monocytes-macrophage lineage including macrophages, dentritic cells and langerhan cells. DV has also been shown to replicate in B- lyniphocytes, moreover, the virus will infect but has not been shown to replicate in 01056

30 both microglia and Kupffer cells. Currently there is no available vaccine for any serotypes of Dengue virus.

The prevention or reduction of DV replication to levels suitable for use as a live recombinant vaccine would involve the incorporation of microRNA binding sites into the viral genome that will bind any ubiquitously expressed microRNA or any microRNA specifically expressed in any one or more or all of the following cells types: monocytes, macrophages, B lymphocytes, dentritic cells and microglia.

Suitable microRNA molecules to which microRNA binding sites could be used are mir-150, mir-155 and mir-146, mir-142, mir-155, mir-15a, mir29a, mir-21, mir-23a. These microRNA molecules are offered as example microRNA molecules and are not an exhaustive list. Binding sites to any microRNA expressed in cells infected by the virus could be used to repress viral gene expression or replication.

The genome of all DV serotypes contains a region of approximately 500bp at the absolute 3 ' un-translated region that would act as a suitable microRNA insertion site. Similarly, the first lOObp of the viral genome in the 5' un-translated region would also act as a suitable insertion site.

Coronaviruses: Severe Acute Respiratory syndrome virus and Infectious Bronchitis Virus Coronaviruses are the largest RNA viruses known and can contain genomes as large as 30Kb. The coronavirus genome consists of a single stranded positive sense RNA molecule that replicates using a series of sub-genomic RNA molecules transcribed from negative strand RNA templates. The individual sub-genomic RNA strands are responsible for producing a single viral protein or poly-protein. All coronavirus genomic copies and sub-genomic RNA molecules contain the same 5' and 3' UTR which is obtained from sequences at the 5' and 3' termini of the genome. Some viruses within the family coronaviridae that are applicable to the invention are:

Avian infectious bronchitis virus (IBV)₅ Bat coronavirus strains BtCo V/l 33/2005/1 A/1 B/512 (2005)/HKU2/HKU3/HKU4- 1 /HKU5- 1/HKU-8/HKU- 9-1 /RfI (2004)/Rp3 (2004), Bovine coronavirus, Equine coronavirus, Feline coronavirus, Porcine epidemic diarrhea virus, Porcine hemagglutinating encephalomyelitis virus, Transmissible gastroenteritis virus, Human coronavirus 229E, Human coronavirus HKUl, Human coronavirus NL63, Human coronavirus OC43, Murine hepatitis virus strain A59, Murine hepatitis virus strain JHM, Severe Acute Respiratory Syndrome (SARS) coronavirus.

Coronavirus disease pathology is caused by infection of the villi of the gut epithelium and/or the cells of the lung epithelium. Restriction of viral replication to specific cell lineage using microRNA binding sites would prevent disease pathology by repressing viral replication in gut and/or lung epithelium. Alternatively, viral replication and consequently viral load during vaccination could be reduced by incorporating microRNA binding sites to any microRNA expressed in lung epithelium.

Suitable insertion locations within the genomic strands of coronaviruses include the 5' and 3' un-translated regions of all genomic strands. Typically such insertions will lie within 400bp of the ends of each viral genomic strand.

Applicability to double stranded RNA viruses focusing on Blue Tongue virus and human rotavirus

Blue Tongue virus (BTV) is a member of the reoviridae family and contains a segmented double stranded RNA genome consisting of 10 segments. During infection of livestock, BTV virus can be isolated from neutrophils, lymphocytes and erythrocytes. However, these sites have not been confirmed at primary sites of replication. By incorporating microRNA binding sites into any one, or more, or all 10 genomic fragments it would be possible to prevent replication in any disease causing tissue. The majority of double stranded RNA replication involves the use of the positive strand only and therefore microRNA suppression would be inserted into the positive strand of the double stranded RNA genome.

This technique could also be applied to all reoviruses and could be used in human rotaviruses (strains A-G) as vaccines using binding sites to any enterocyte specific microRNA, or any microRNA expressed in enterocytes, on any or all 11 double stranded RNA genomic segments. Influenza virus

Viruses within the family Orthomyxoviridae all contain negative sense segmented (mature particles contain multiple genomic strands of differing sequence) RNA genomes. Such viruses include Influenza A, Influenza B, Influenza C, Isavirus (Salmon Anemia Virus) and Thogotavirus (THOV). THOV contains 6 genomic segments/strands whilst all other member viruses contain 8 genomic segments. Infection with viruses of the Influenza genera is localised to ciliated and/or non- ciliated cells of the upper and/or lower lung epithelium. Preferential infection of specific lung epithelial cells is dependent on the receptor properties of each virus. Therefore, the invention refers to the prevention or reduction of viral replication in all of these cell types of the lung epithelium. Current vaccination to Influenza includes the use of an inactivated cold-adapted virus and the use of a cold-adapted live virus administered via a nasal aerosol.

Rather than completely restricting viral replication to cell lineage using mieroRNA binding sites, viral replication and consequently viral load during vaccination could be reduced by incorporating microRNA binding sites to any mieroRNA expressed in lung epithelium. The multiple segmented genomes of members of the Orthomyxoviridae family allows one, or more, multiple microRNA insertions to be made into all, or less, segments on the viral genome. The binding sites used in each segment of the genome could bind to the same, or different, microRNAs expressed in lung epithelium. Using different microRNA binding sites may decrease recombination and deletions between stands on the virus due to decreased inter-strand homology. Moreover, influenza exhibits a high frequency of mutation and therefore the use of microRNA binding sites in both the sense and atiti- sense orientation in the negative strand of the genome will enhance the safety of any vaccine. MicroRNA genes or clusters which demonstrate the highest expression are not tissue specific and therefore many multiple microRNA molecules could be used to induce suppression of viral replication. Suitable microRNA molecules ubiquitously expressed include mir-98, mir-15a/mir-15, mir-23a/mir-23. These microRNA molecules are offered as example microRNA molecules and are not an exhaustive list. Binding sites to any microRNA expressed in cells infected by the virus could be used to repress viral gene expression or replication. Suitable insertion locations within the genomic strands of Influenza viruses include the 5' and 3' un-translated regions of all genomic strands. Typically such insertions will lie within 300bρ of the ends of each viral genomic strand.

Applicability to DNA viruses

Kaposis Sarcoma and Epstein Barr virus

The use of live DNA vaccines has proven successful in the eradication of small pox using the closely related vaccinia virus. DNA viruses generally do not frequently show transversion of transition mutations and, therefore, any vaccines derived from such viruses are more genetically stable than any RNA virus. Kaposi's sarcoma-associated virus (KSHV) is a herpesvirus (HHV-8) with a 165 Kb double stranded genome. KSHV causes both Kaposi's sarcoma and primary effusion lymphoma (PEL) following infection of endothelial and cells of a B-cell origin, respectively. In these tumours, lytic viral reproduction is not observed; moreover, every KSHV derived tumour cell expresses three latency associated transcripts that are essential for viral latency. These are termed v-FLIP, v-cyclin, and latency- associated nuclear antigen (LANA) and all expressed from the same promoter and are responsible for tumourogenesis. Complete or partial deletion of these genes can prevent latency and would, therefore, be beneficial to any KSHV derived vaccine. The transition from latency to lytic infection of KSHV has been shown to depend on the trans-activating functions of the viral protein RTA encoded by ORF50. This protein is essential for viral replication and productive virion release. Given that KSHV infects both B cells and endothelial cells and that lytic infection of B cell populations would be detrimental to any individual treated with a live replicating KSHV vaccine, microRNA suppression of RTA transcripts in lymphoid tissues could be employed. With the deletions above, the virus would be unable to perform tumourogenesis and exhibit latency but would replicate in endothelial tissue to elicit a strong cell mediated immune response.

This technique could also be used to prevent Epstein-Barr virus (EBV/HHV- 4) expression in cells of the B cell lineage by suppressing the trans-activating protein EBNA-I and possibly other genes essential for both B cell lytic infection and latency. This modification, coupled with deletions of viral protein coding and viral microRNA genes to prevent latency would allow the production of an effective EBV vaccine.

MicroRNAs capable of preventing expression in cells of the B cell lineage are mirl42, mirl 50, mirl 55 and mirl46. These microRNA molecules are offered as example microRNA molecules and are not an exhaustive list. Binding sites to any microRNA expressed in cells infected by the virus could be used to repress viral gene expression or replication.

African Swine fever virus African Swine fever virus is the only member of the family Asfarviridae and contains a large (170 Kb) double stranded DNA genome. There are no current treatments or prophylactic vaccines to treat this disease which causes high mortality in infected pig populations. Outbreaks have so far occurred in Spain, Portugal, France, Belgium, Cuba and the Dominican Republic and the virus is endemic in sub- S aharan Africa.

Viral replication is observed mainly in cells of the monocytes/macrophage (reticuloendothelial system) lineage and also to some extent in the aortic endothelium. The disease causes massive haemorrhaging and can kill within a week of initial infection. Unlike many other large DNA viruses no closely related and less pathogenic viruses have yet been found that could act as a vaccine.

The genome of ASFV replicates in the cytoplasm of an infected cell and as such requires it own transcription and replication machinery. Consequently, ASFV has been shown to contain multiple sub-units of an RNA polymerase that transcribes the genes of the virus in the cytoplasm and consequently these genes are essential for viral replication. Other genes essential for replication include the DNA polymerase and structural proteins.

Partial or complete silencing of the mRNA transcripts that produce these proteins would efficiently prevent replication and can be achieved in cells of the monocyte or macrophage lineage using microRNA binding sites to the following microRNA molecules. Mir 142, mir-155, mir-15a, mir29a, mir-21, mir-23a. These microRNA molecules are offered as example microRNA molecules and are not an exhaustive list. Binding sites to any microRNA expressed in cells infected by the virus could be used to repress viral gene expression or replication.

Hepatitis B virus Hepatitis B virus (HBV) is an enveloped virus of the Hepadnaviridae virus family and contains an approximately 3.2Kb DNA genome. However, the genome consists of both double and single stranded DNA and replicates though a RNA intermediate without chromosomal integration. This replication strategy consequently involves the use of a virally encoded reverse transcriptase which reverse transcribes full length RNA copies of the genome into the aforementioned DNA duplex. The genome of HBV contains four genes termed HBVgpl, HBVgp2, HBVgp3, HBVgp4. These genes are transcribed from a covalently closed circular form of the genome and produce 7 proteins. These are the S protein (HBVgp2), X protein (HBVgp3), precore/core protein (HBVgp4), core/E antigen protein (HBVgp4), polymerase protein (HBVgpl), large S protein (HBVgp2) and the middle S protein (HBVgpl). All of these genes are essential for replication of HBV and demonstrate overlapping genomic coding regions.

HBV infection is mediated through contact with infected blood or bodily fluids and viral infection is primarily observed in the hepatocytes. The majority of cases of HBV infections are cleared quickly with no long term consequences, however, some patients appear unable to clear the virus and consequently develop a chronic infection. The persistent damage inflicted by immune suppression of viral replication can cause liver cirrhosis and potentially hepatocellular carcinoma. Currently, vaccination against HBV involves administration of three separate injections of the HBV surface antigen (HbsAG -Spike protein) delivered at 0, 1 and 6 months. This vaccine is successful in the majority of cases however, people who do not develop immunity (approximately 5-10%) are still susceptible to infection. The source of the protein used as the antigen is from the serum of chronically infected individuals or, more commonly, through recombinant DNA technology. Live Hepatitis B viral vaccines are not used for vaccination however by using microRNA binding sites to silence or limit replication in hepatocytes a live recombinant viral vaccine could be generated. The viral genome of HBV is produced from RNA copies of the viral genome that are longer than the genome itself. These copies also serve as mRNA for the polymerase gene which reverse transcribes the RNA into the DNA viral genome. The replication stratergy employed by HBV would therefore allow any microRNA binding sites incorporated into the genome to both silence the polymerase gene and also lower the level of RNA genomic copies available for reverse transcription. Moreover, by incoropating microRNA binding sites into the 3' and/ 5' UTR of other HBV genes these may also be selectively silenced as well. Such genes include HBVgp3 (X protein) and HBVgp4 (precore/core protein and core/E antigen protein). The expression of spike proteins would ideally remain unaffected given the success of previous vaccines based on using the surface protein as an antigen.

Suitable insertion sites would be selected based on the success of producing a virus which still retains the ability to replicate in a cell line that does not express the microRNA which may repress the viral replication in vivo. Sites cannot be specifically described because coding regions of all HBV genes overlap with each other and therefore suitable insertion sites cannot be accurately predicted. An insertion site that may allow production of replication competent virus would be between the HBVgp3 3' end and the HBVgp4 5' end. This region overlaps by 24 base pairs and could be engineered to split the genes by allowing the HBVgp3 protein to retain the normal 3' end and also allow the incorporation microRNA binding sites downstream of the HBVgp3 coding sequence. The 5' end of the HBVgp4 protein could be engineered to contain the normal 5' coding sequence by insertion of a second copy of the 24 bp region lost by splitting the two genes. Alternatively, the 5' end of the HBVgp4 gene may be retained whilst the 3' 24 base pairs of the HBVgp3 gene may be engineered by a new insertion.

MicroRNA molecules that may prevent, or reduce viral replication and protein expression in hepatocytes will be mir-122/mir-122a or any microRNA which is expressed in hepatocytes at levels capable of producing the desired repression level. These microRNA molecules may be ubiquitously expressed or tissue specific. AU serotypes of HBV are applicable to this invention. Including adr, adw, ayr, ayw. All eight genotypes (A-H) are applicable to this invention. Experimental Examples

We have engineered a hepatocyte-safe wild type adenovirus 5 (Ad5), which normally mediates significant toxicity and is potentially lethal in mice. To do this we have included binding sites for hepatocyte-selective microRNA122a within the 3 ' UTR of the ElA transcription cassette. Imaging versions of these viruses, produced by fusing ElA with luciferase, showed that inclusion of microRNA122a binding sites caused up to 80 fold decreased hepatic expression of ElA following intravenous delivery to mice. Animals administered a ten-times lethal dose of wild type Ad5 (5 x 10¹⁰ viral particles/mouse) showed substantial hepatic genome replication and extensive liver pathology, while inclusion of 4 microRNA binding sites decreased replication 50-fold and virtually abrogated liver toxicity.

This modified wild type virus retained full activity within cancer cells and provides a potent, liver-safe oncolytic virus.

Evaluation of potency of microRNA122a regulation in vitro

To assess the repression capabilities of microRNA- 122a, CMV promoter- driven luciferase plasmids containing 0, 4 and 8 sense or 4 anti-sense microRNA binding sites (representative structures shown in Figure 6) were transfected into HEK-293, OVCAR-3 and Huh7 cell lines using DOTAP (Roche) and luciferase activity was measured by luminometry after 24 h. The presence of the microRNA binding sites had no effect on luciferase levels detected in the microRNA122a negative cell lines HEK-293 and OVCAR-3 (Figure 7). In contrast, in microRNA 122a-positive Huh7 cells, luminescence was decreased from 7.9xlO⁵ RLU/μg (anti-sense control plasmid) to 9.9xlO⁴ RLU/μg (4 x microRNA binding sites, P=O-OOl)) and 3.4xlO⁴ RLU/μg (8 microRNA binding sites, P=0.001). The inclusion of 4 anti-sense microRNA binding sites did not affect luciferase activity compared to the unmodified control plasmid in any cell type. Whilst the inclusion of 8 microRNA binding sites did show improved repression in comparison to 4 binding sites, we decided to use 4 binding sites for future use in view of the repetitive nature of the insertion and to minimise the likelihood of viral recombination. Evaluation of potency of microRNA122a regulation in vivo

Luciferase expression from the microRNA-controlled plasmids was assessed in murine livers in vivo, using an IvislOO imaging system. Plasmid vectors were delivered at equimolar amounts by hydrodynamic delivery and imaging was performed at 8, 24 and 48 h post injection. Control CMV promoter-driven plasmids gave high levels of transgene expression after 8 h (2.7 x 10^π RLU) while inclusion of 4 microRNA binding sites in the same plasmid decreased expression to 5.7 x 10⁹ RLU, a 47-fold decrease in expression (Figure 8). Total levels of luciferase expression fell substantially over the next 40 h, although the differential expression increased up to 129-fold (/^=0.0064) after 48h.

Plasmids containing the El A promoter and ElA coding sequence were engineered to generate an El A-luciferase fusion transcription cassette. This vector was then further modified to contain four binding sites to microRNA 122a to allow in vivo imaging of ElA expression (Figure 6). Following hydrodynamic delivery of equimolar amounts of both vectors, expression from the plasmid producing the ElA- luciferase fusion protein (with no microRNA sites) was much lower than from the equivalent pCMV vector, probably reflecting relatively weak activity of the ElA promoter in murine cells, however the inclusion of four microRNA sites within this plasmid again mediated a significant decrease in expression (86-fold after 8 h, It was noticeable that luciferase expression from the fusion protein decreased more rapidly with time than from the pCMV-driven vectors, perhaps reflecting the ability of El A to negatively regulate its own promoter.

MicroRNA122a-binding sites do not affect adenovirus activity in mirl22a- negative cells in vitro and in vivo

Adenoviruses containing El A-luciferase fusion constructs on a background of wild type Ad5 were used to infect microRNA 122a-negative A549 and OVCAR-3 cell lines in vitro. Luciferase activity, which directly correlates with viral ElA levels, increased slowly between 8 and 24 hours and then showed a more rapid rise that was sustained up to at least 72 h (Figure 9 B&C). This profile of luminescence may reflect initial transcription from the input viral genomes that increases rapidly following viral genomic replication. The microRNA insertion into the 3 ' UTR did not affect the profile of luciferase expression in these cells, suggesting the modification did not influence the stability of mRNA encoding the El A-luciferase fusion protein, nor did it inhibit virus replication in these microRNA 122a-negative cells. To ascertain whether the microRNA insertion would also be inactive in microRNA122- negative cells in vivo, viruses (IxIO¹⁰ v.p.) were injected subcutaneously in Balb/C mice (n=3) and animals were imaged after 24 h. Results demonstrated no significant difference between the expression from the two viruses (data not shown) suggesting no effects of the microRNA at the subcutaneous site.

MicroRNA122a-binding sites decrease activity of ElA-luc-Ad5 viruses in mirl22a-positive cells in vitro and in vivo

Adenoviruses encoding the El A-luciferase protein with and without four microRNA binding sites were used to infect a monolayer of the mirl22a positive cell line Huh7. El A-luciferase expression was monitored by luminometry from 6 h to 72h post-infection (Figure 9D). Luciferase expression from the Ad5-El A-Luc (which contains no binding sites for microRNA 122a) showed a small but significant rise between 0 and 24 h (reaching l.lxl O⁵ RLU/μg protein) and then increased rapidly, rising to 1.7x10⁶ RLU/μg protein by 72 h. This suggests ElA transcription and replication proceeded similarly to the situation in A549 and OVCAR cell lines. In contrast, Ad5-El A-Luc-mir virus (which contains a concatamer of four binding sites for microRNA122a) showed significantly less luciferase expression at all time points, reaching only 6.3 x 10⁴ RLU/μg after 72 h (P-0.0001 for both 48 and 72h). The differential in luciferase expression between the viruses with and without microRNA binding sites increased over time, suggesting decreased genome replication of Ad5-El A-Luc-mir compared to Ad5-El A-Luc. In order to confirm that this differential in luciferase expression was due to mir-122 knockdown of ElA, a precursor RNA mimic of mir-122 (Ambion) was introduced into A549 cells to simulate hepatocyte expression. Ad-El A-Luc-mir and either the mirl22 pre-cursor, or negative control pre-mir (Ambion) were added to cells and luciferase readings performed after 24h. Results showed that the introduction of the pre-mir 122 reduced luciferase, and therefore ElA, expression from 9.2 x 10⁴ RLU (negative control pre- mir) to 3.4x10³ RLU (P=OX)OOl, Figure 9B).

To assess the in vivo activity of these viruses and to observe the effects of time on ElA expression over 96 h, 5 x 10¹⁰ vp of Ad5-E1A-Luc and Ad5-E1A-Luc- mir were injected intravenously into Balb/C mice. Animals were imaged at 6, 24, 48, 72 & 96 h (Figure 10). After 6 h, Ad-El A-Luc showed a luminescence signal of 1.6xlO⁸ RLU whilst Ad-ElA-Luc-tnir showed only 3.OxIO⁶, a differential of 52- fold). Interestingly, the signal from the Ad5-El A-Luc treated mice increased by 2.5xlO⁹ RLU between 48 and 72 h (Figure 10F) possibly reflecting a wave of virus replication. At the same time the microRNA regulated virus showed only a relatively small increase (a rise of 3.4x10⁷ RLU). After 96 h the differential expression between the viruses with and without microRNA sites had reached 80 fold.

MicroRNA regulation of wild type Ad5 (Ad5WT) reduces genomic replication and hepatic toxicity

In order to assess the effects on hepatic toxicity of including microRNA122a binding sites within wild type adenovirus, 5xlO¹⁰ v.p of Ad5WT and Ad5-mir were injected intravenously to Balb/C mice. One mouse in the study which received Ad5WT became hunched and immobile, and was sacrificed after 60h with visible hepatic pathology. Remaining mice were exsanguinated under anaesthesia 72h post- injection and blood was allowed to clot. Serum from both groups was tested for Alanine Aminotransferase (ALT) levels and Aspartate Aminotransferase (AST) to assess hepatic damage. Mice administered wild type Ad5 showed significantly increased ALT levels (90 times higher than control mice treated with PBS,

P=0.0001; Figure 1 IA) suggesting substantial liver damage had occurred. Mice administered Ad5-mir showed approximately 15 -fold less serum ALT (5 times normal) demonstrating that less liver toxicity had occurred with this virus. AST readings demonstrated similar results with a 17 fold decrease in AST in serum from mice administered Ad5-mir compared to serum from mice receiving Ad5WT

(P=O.0002, Figure 1 IA). To evaluate viral replication and tissue damage, livers were cut in half and one half of each was used for histological analysis, while QPCR was performed on the other half. Livers taken from mice administered wild type Ad5 showed an average of 2x10⁹ genomes/mg liver (wet weight; Figure 1 IB). In the total liver this represents approximately 60-fold more genome copies compared to the total amount of virus originally injected, suggesting significant genome replication. In contrast, livers from mice administered Ad5-mir showed only 8x10⁷ virus genomes per mg liver, representing less than a doubling compared to the input dose (P=O-OOOl for Ad5-mir compared to Ad5WT). These data confirm that the microRNA suppression of El A is capable of significantly reducing replication of the virus genome in murine liver in vivo.

Histological analysis showed a dramatic difference between animals administered wild type Ad5 and those administered Ad5-mir. Wild type Ad5 induced vacuolation, haemorrhaging and abnormal nuclear morphology, while livers from mice administered Ad5-mir showed very little pathology, with some mice showing no aberrant morphology in any liver section (Figure HC). Histological images of liver from a mouse administered 5x10¹⁰ vp of a non-replicating adenoviral vector are presented for comparison, showing similar or slightly greater liver pathology than was induced by Ad5-mir.

The maximum tolerated dose of Ad5WT given i.v. is reported as about IxIO⁹ PFU, and this was confirmed in studies using nude mice bearing HepG2 human hepatocellular carcinoma xenografts (data not shown). Animals were found to tolerate higher levels of Ad-mir (6x10¹⁰ v.p., 9xlO⁹ PFU) with only mild weight loss, although when this dose of Ad-mir was administered on two consecutive days, all mice were showing signs of virus-related toxicity by day 4 following the first injection. These mice were put down and the livers demonstrated macroscopic signs of viral liver damage. It therefore appears that, in tumour bearing animals, the maximum tolerated dose of Ad-El A-Luc-Mir lies between 6xlO¹⁰ and 1.2elOⁿ.v.p./mouse (9xlO⁹ - 1.8xlO¹⁰ pfu). Discussion

In this study we engineered wild type Ad5 to avoid its major toxicity in murine liver by including four binding sites for hepatocyte-specific microRNA122a within the 3'UTR of ElA. To measure ElA expression non-invasively we introduced a luciferase coding region 3' to the ElA coding region of wild type virus in order to produce a contiguous El A-luciferase expression cassette, where ElA splicing would produce a series of El A-luciferase fusion proteins. This novel virus (including a modified version containing 4 microRNA122a binding sites in the ElA 3' UTR) produced strong luciferase activity in vitro and in vivo that reported ElA protein levels clearly, enabling non-invasive real-time assessment of protein translation including the effects of virus genome replication. Measuring ElA protein in this way is a more reliable indicator of microRNA activity than measuring ElA mRNA, since microRNA regulation is known to affect protein translation via multiple pathways. However, given that our microRNA target sites are precisely complementary to mirl22a it is likely that argonaut 2 -mediated RNA cleavage is responsible for the majority of the knockdown observed. While the presence of the luciferase sequence slightly decreased the rate of cell killing in vitro, compared to the corresponding virus without luciferase, a complete cytopathic effect was still achieved in permissive cells after one extra day. This suggests that the fusion proteins retain all essential ElA functions. This is perhaps unsurprising given that ElA protein has been shown to still operate despite significant deletions and insertions, lacking both enzyme activity and significant secondary structure.

Wild type Ad5 is normally capable of an abortive genome replication cycle in murine liver in vivo, where it mediates considerable and sometimes lethal hepatotoxicity. It was unclear whether microRNA regulation could successfully control Ad5, since the DNA genome is not a direct target for microRNA recognition and it is known that even small amounts of El A translation can lead to genomic replication, which will then provide a template for more transcription providing a greater challenge for microRNA control. Nevertheless, although ElA production in microRNA 122a-positive Huh7 cells in vitro was decreased only about 95% following introduction of 4 microRNA122a-binding into the ElA-luciferase reporter virus, in vivo luciferase imaging suggested a greater suppression of ElA expression by microRNA122a, showing a 50-fold differential after 6h that rose to 80-fold after 96h. This may reflect a higher expression of microRNA122a in murine hepatocytes in vivo than in human Huh7 cells. To complement the El A reporter luciferase data, hepatic replication and toxicity was also assessed using wild type Ad5 and compared with a 'wild type' modified to contain four microRNA122a sites. After 72h the serum ALT was decreased 15-fold for the microRNA-containing version compared to wild type, hepatic morphology showed far less evidence of toxicity (many sections appearing normal) and the number of viral genomes found in liver was decreased by a factor of 25. These findings are consistent with those using the ElA-luciferase reporter viruses, and suggest that inclusion of the microRNA122a-binding sites had a dramatic effect on hepatic activity and toxicity of the virus. It is worth noting that in this study the viruses were applied at dose in vivo (5x10¹⁰ vp/mouse), well above the lethal dose for wild type Ad5, hence this regulatory strategy appears capable of controlling the activity of significant quantities of virus. Also of note is the ability of microRNA122a in mouse liver to tightly regulate the very high levels of El A- luciferase fusion protein achieved following hydrodynamic plasmid delivery (Figure 8), some 10-fold higher than those shown by the viruses. This suggests that the doses of virus used in this study do not even come close to exceeding the regulatory capacity of microRNA122a. When even higher virus doses were applied, the maximum tolerated dose of Ad5-mir was estimated as between 6x10¹⁰ and 1.2elO^u.v.p./mouse (9xlO⁹ - 1.8xlO¹⁰ pfu), and these doses presumably allow the virus to break through regulation by hepatic mirl22a. Nevertheless these doses are high, affording a range of doses where the virus may be applied therapeutically.

MicroRNA-based virus regulation strategies should find a variety of applications in biotechnology. Their small size (an individual site is typically 22 bp) allows insertion of multiple binding sites, recognising diverse microRNAs, without compromising virus packaging efficiencies. In addition the small insertion size and typical proximity to essential virus genes and regulatory regions (e.g the ElA poly A signal) decreases the likelihood of propagating deletions. Hence a range of stable and versatile agents may be produced using this approach. Engineering of microRNA-regulated luciferase reporter plasmids

Luciferase reporter plasmids sensitive to microR]SfA122a were prepared by introducing concatamers of binding sites for microRNA122a (4 or 8 sense or 4 antisense binding sites) into the 3'UTR of the luciferase transcription cassette. A CMV-driven luciferase-expressing plasmid vector pCIKLux was cleaved with Notl, oligonucleotides were annealed at 95°C, cooled and ligated into dephosphorylated vector. This produced vectors pCMV-Luc-mirl22aX4 (shown in Figure 1), pCMV- Luc-mirl22aX8 and pCMV-Luc-mirl22anti, together with the control (hereafter referred to as pCMV-Luc) which contained no microRNA122a binding sites.

The coding region for the C terminal half of El A was PCR amplified using Accuprime PFX (Invitrogen) and primers (forward ATT ATA AGA TCT GGA TAG CTG TGA CTC CGG TCC TTC, reverse TAT TCC ATG GAT GGC CTG GGG CGT TTAC) using a plasmid containing wild-type Ad5 as template. These primers introduced unique BgIII and Ncol restriction sites to the 5' and 3 ' termini respectively. The purified PCR product was cleaved with BgIII and Ncol and cloned into pCMV-Luc and pCMV-Luc-mirl22aX4 described above, using the same enzymes, producing a fusion between the C terminal half of El A and luciferase, including zero or four microRNA sites in the 3' UTR. These products were subcloned using PshAl and Hpal into a plasmid pAd5-Kpnl (produced by restriction of wild type Ad5, see below) to produce plasmids (pAd5-Kpnl-ElA-Luc and pAd5-Kpnl-El ALuc-mirl22aX4) in which ElA was C-terminally fused to the luciferase coding sequence. The overall scheme of plasmid cloning is shown in Figure 6.

Cloning of microRNA-regulated wild-type Ad5

Wild-type Ad5 plasmid containing kanamycin resistance was cleaved with BstZ17I and recircularised by blunt ended ligation. This vector (Ad5-BstZ17I) was then further cleaved and re-ligated using Kpnl to increase the number of unique restriction sites available for further cloning. This vector is referred to as Ad5-Kpnl . The 4 microRNA binding sites for mirl22a were PCR amplified from pCMV-Luc- 122aX4 (described above) to introduce Dral sites to each end. The purified PCR product was cleaved with Dral and blunt end ligated into Ad5-Kpnl which was cleaved with Hpal. Insertion of microRNA binding sites downstream of ElA was confirmed by DNA sequencing. Ad5-Kpnl-mirl22aX4 was reconstituted to Ad5- BstZ17I using the Kpnl gel-extracted fragment from Ad5-BstZ17I. To generate full size adenovirus genome Ad5-BstZ17I-mirl22aX4 was cleaved with BstZ17I, dephosphorylated and subject to homologous recombination with full size wild type Ad5 vector and selected on kanamycin. Insertion of microRNA binding sites was confirmed by sequence analysis. Restriction digestion of the resulting vector confirmed full size adenovirus had been recovered.

Cloning of microRNA-regulated hiciferase reporter based on wild type Ad5 pAd5-Kpnl-ElALuc-mirl22aX4 and pAd5-Kpnl-El ALuc were reconstituted to Ad5-BstZ17I using the Kpnl gel-extracted fragments from Ad5- BstZ17I. To generate full size adenovirus genome Ad5-BstZ17I-El ALuc- mirl22aX4 and Ad5-BstZ17I-ElALuc were cleaved with BstZ17I, dephosphorylated and subject to homologous recombination with full size wild type Ad5 vector and selected on kanamycin. Insertion of microRNA binding sites was confirmed by sequence analysis. Restriction digests of the resulting vectors confirmed full size adenoviruses had been recovered. Genomic structures and sizes of the viruses are shown in Figure 9A.

Adenovirus preparations.

All adenoviruses were grown in A549 cells, purified by double banding in CsCl gradients with benzonase treatment after the first banding. Viral particle (vp) number was determined by measuring DNA content using a modified version of the PicoGreen assay (Invitrogen, Paisley, UK). TCID50 calculated with the KARBER statistical method [1] was used to estimate the adenovirus titer (TCID₅₀ units/ml) and corrected to determine plaque forming units/ml (pfu/ml). Adenovirus preparations characteristics are as follows: Ad5 wild type: 1.13 x 10¹²vp/ml, 1.98 x 10¹¹ pfu/ml andparticle:infectivity (P:I) ratio of 5.6; Ad5mirl22aX4: 1.29 x 10¹² vp/ml, 2.01 x 10¹¹ pfu/ml and particlerinfectivity (P:I) ratio of 6.4. All virus preparations were screened for endotoxin and verified negative prior to use.

Maintenance of cell lines

Human hepatocellular carcinoma Huh7 cells, A549 lung carcinoma cells,

OVCAR3 ovarian cancer cells and HEK293 human embryonic kidney cells were obtained from the European Collection of Cell Cultures (Porton Down, UK), and maintained in DMEM with 10% foetal bovine serum (FBS) (PAA Laboratories, Yeovil, UK) including penicillin (25 U/ml) and streptomycin (10 mg/ml).

Luciferase expression assays in vitro

Cells were seeded in triplicate in 12 well plates. After 24h plasmid DNA (0.5μg) was added to 50 μl of HBS buffer and mixed with 2.5 μl DOTAP reagent (Roche) also in 50μl sterile HBS. The complex was incubated at room temperature for 30 min. lOOμl of transfection mixture was added to each well and incubated at 37°C for 4h. Cells were washed with PBS and incubated with DMEM containing 2% FBS. 24h following transfection media were removed and 150 μl reporter cell lysis buffer (Promega) was added to the cells. Cells were then frozen at -80⁰C for >1 h before thawing. Luciferin (25 μl) (Promega, Southampton, UK) was added to 25 μl aliquots of cell lysate and relative luminescence was measured by luminometry (Lumat LB 9507, Berthold Technologies, Redbourn, UK).

Pre-mir 122 transfection

A549 cells were seeded at 5x10⁴ cells per well and incubated overnight. Pre- mirl22 (Ambion) and pre-mir negative control (Ambion) were re-suspended to

50μM and then further diluted 10 fold. 3μl per well of this dilution of each pre-mir was added to 22 μl Opti-MEM medium (Invitrogen). 2μl per well of NeoFx transfection reagent (Ambion) was added to 23 μl Opti-MEM solution. Pre-mir/Opti- MEM was mixed with the NeoFx/Optimem and allowed to complex for 10 minutes. A549 cells were washed with PBS and the transfection mixture added to cells at a total volume of 50μl. Total amount of pre-mir is 15 pmol/well. Immediately following transfection Ad-El A-Luc-mir was added at 10 vp/cell in 450μl DMEM media (10% FCS). 18h later, 30 pmol/well of pre-cursor mirl22 and negative control pre-cursor microRNAs were added to each well in addition to the 500μl described above. Luciferase readings were performed at 24h.

Real time (quantitative) PCR (Q-PCR) for Ad5

The Q-PCR methodology for measurement of adenoviral particles has been previously described [2]. Viral DNA from infected cell or tissue samples were extracted using a mammalian genomic DNA miniprep kit (Sigma). Reactions were performed using Applied Biosystems master mix following the manufacturer's protocol. The cycles were as follows: 94°C 10 min; 40 times (94°C 30 s, 60°C 1 min). Primers sequences for targeting Ad5 fiber are: FW- TGG CTG TTA AAG GCA GTT TGG (Ad5 32350-32370 nt) and RV- GCA CTC CAT TTT CGT CAA ATC TT (Ad5 32433-32411 nt) and the TaqMan probe- TCC AAT ATC TGG AAC AGT TCA AAG TGC TCA TCT (Ad5 32372-32404 nt), dual labeled at the 5' end with 6-carboxyfluorescein and the 3' end with 6-carboxytetramethylrhodamine. The results were analyzed with the Sequence Detection System software (Applied Biosystems). Standard curves for tissues and cells were prepared by spiking samples of cell lysate or tissue homogenate with serial dilutions of known concentrations of virus particles and then extracting and analysing each sample separately by Q-PCR as described above.

Measurement of Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)

Blood was taken from mice by cardiac puncture and allowed to clot (15 min, room temperature) and spun at 1200 g for 10 min. Serum was isolated and immediately frozen at -20°C). Samples of thawed serum (5μl) were added to ALT reagent (995μl, Microgenics) or AST reagent (995μl, Microgenics) in a 1 ml quartz cuvette, incubated at 37⁰C and the change in absorbance (340 nm) per minute was monitored. Units of ALT and AST activity were calculated according to the manufacturer's instructions.

Assessment of hepatic expression of plasmids in mice Plasmids were administered by hydrodynamic injection (0.8 pmole/mouse, using a 10% body volume of PBS administered over 5-10 s with a 27 gauge needle) into the tail veins of Balb/c mice. Non-invasive measurement of luminescence was performed after 8, 24 and 48h using an WIS 100 system (Xenogen, MA) under isofluorane anaesthetic. Luciferin was administered by intraperitoneal injection (15.8 mg/ml in PBS, 100 μl/mouse) 4 min prior to imaging. Flux levels were analyzed with Living Image Software (Xenogen, MA).

Evaluation of the activity of adenoviruses containing microRNA binding sites in vivo Clodronate was a gift ofRoche Diagnostics GmbH, Mannheim, Germany. It was encapsulated in liposomes. Viruses were administered intravenously (unless otherwise indicated) and all animals were pretreated with bisphophonate liposomes (lOOμl/mouse, 24h before. For imaging expression of ElA encoded within replication-competent Ad5, El A-luciferase reporter viruses with and without 4 binding sites for mirl22a (Ad5-El A-luc and Ad5-El A-luc-mir) were injected intravenously to Balb/c mice (5x10¹⁰ v.p./mouse). Animals were imaged after 6, 24, 48, 72 and 96h as described above. To study the ability of microRNA 122a-binding sites included within wild type A5 to decrease hepatic replication of virus genomes and tissue damage, 5x10¹⁰ v.p./mouse of Ad5WT and Ad5-mir were injected i.v. Animals were monitored twice daily and sacrificed after 72h for measurement of genome replication (by QPCR) and assessment of pathology (by histological analysis). Histology

The left liver lobe from each mouse was immersed in 10% buffered formalin overnight at room temperature, embedded in wax and sectioned using a vibratome. Sections were stained with haematoxylin and eosin and analysed by light microscopy at x 40 magnification.

Statistical Analysis

In vitro data are expressed as the mean of 3 replicates ± standard deviation unless otherwise stated. In vivo data are expressed as the mean of four replicates ± standard deviation, except using the plasmid pCMV-Luc-Mir 122a for which n=3. Significance was evaluated using t-test and denoted on the graphs as * PO.05, ** PO.005, *** PO.0005.

Anti-cancer efficacy ofmicroRNA regulated adenovirus Pharmacodynamics led dose escalation study of Ad-mirl22

Sequential half-log escalating doses of Ad5-WT and Ad5-mirl22 were administered intravenously to nude mice bearing mirl22 negative HepG2 human hepatocellular carcinoma xenografts, with serum ALT measured after each dose. The starting dose for both viruses was 6xl0⁹vp/mouse, corresponding to 8.8x10⁸ pfu for Ad5-WT. The maximum tolerated dose (MTD) for Ad5-WT has previously been described as IxIO⁹ pfu. Each dose consisted of 90% test virus (either Ad5WT or Ad5mirl22), and a 10% spike of Ad5-ElA-Luc-mirl22 (Ad5- mirl22 in which El A is C-terminally fused to luciferase). This modification allowed non-invasive monitoring of virus activity in real time. Two days following administration of 6x10⁹vp Ad5-WT, mice showed dramatically elevated ALT (>1000 Units/L) suggesting significant hepatic toxicity. Imaging showed high levels of hepatic luciferase expression, confirming significant virus activity in the liver, with no apparent signal from the tumour. Although the ALT values fell steadily over the next few days (days 5-8), several animals showed significant weight loss and one had to be put down (falling to less than 85% of its starting weight). Accordingly this dose was taken as the MTD of Ad5-WT, and treatment was not escalated further.

In contrast, two days following administration of 6x10⁹ vp Ad5-mirl22, mice showed ALT readings similar to PBS control mice (Figure 12). Imaging data confirmed this result with little to no hepatic expression. No tumour localisation was observed with this dose.

The dose was therefore increased by a half log to 2xl0¹⁰vp, three days after the first injection. Imaging data at day 5showed low levels of virus activity in both tumour and liver, although absolute values varied between mice (data not shown). ALT values were more consistent between mice, and showed a minor increase above the level from control animals. On day 6 following the first injection the dose was further increased by a half log to 6xl0¹⁰vpImagmg now showed significant virus activity in the tumours, although this was coupled with measurable activity also in liver. ALT readings interestingly only showed a small increase from the previous dose. The dose was not increased further in these mice. This study confirmed that 6xl0¹⁰vp Ad5-mirl22 was safe as a delivery dose, although greater selectivity for tumour infection was achieved at lower doses

Assessment of tumour size in these animals was performed 41 days after the start of treatment. The single dose at MTD of Ad5-WT had no significant effect on tumour volume. However, the three doses of Ad5-mirl22 had caused a significant reduction in tumour size compared to controls (P=O.02) and those mice receiving Ad5-WT (P=0.05). These data show that the reduced toxicity of Ad5-mirl22 allowed use of doses more than 10-fold above the maximum dose of Ad5-WT, which correlated with increased anti-cancer efficacy. In order to confirm the MTD for Ad5-mirl22 mice bearing HepG2 xenografts were injected with 2 consecutive doses of 6x10¹⁰Vp (24hrs apart). All mice showed significant toxicity including weight loss and lethargy 3 days after the second injection. Blood ALT analysis revealed that these mice had hepatic toxicity equal to lower, but fatal, doses of Ad5-WT. Imaging of these mice showed high levels of hepatic virus gene expression (data not shown) suggesting virus replication. We determined the MTD for Ad5-mirl22 to be between 6xlO¹⁰ and 2xlOⁿ. These mice were euthanized due to toxicity. Repeat administration of Ad-mirl22a

To further assess the anti-tumour activity of Ad5-mirl22, nude mice bearing established HepG2 xenografts were administered 2x10¹⁰Vp via intravenous injection on day 0, 3, 19 and 22. Tumour sizes were monitored for efficacy and mice were euthanized when tumour volume reached 1000mm³. Mice administered Ad5-mirl22 showed a significantly reduced tumour volume from day 20 compared to PBS controls. Light images of all mice in treatment from both control and Ad5-mirl22 groups after 32 days are shown in figure 13B. Pictures show substantial tumour volume in control groups whilst the mice treated with Ad5-mirl22 show reduced tumour burden.

Kaplan Meier analysis of mice administered Ad5-mirl22 showed increased survival with all mice surviving longer than all controls. These data show that the repeat administration of Ad5-mirl22 at doses above the dose range of Ad5-WT can have significant anti-cancer efficacy. No toxicities were observed in this study.

Discussion

Previously we have shown that Ad5-WT can be engineered so that ElA mRNA translation was inhibited specifically in hepatocytes. This was achieved by inserting four binding sites for the hepatocyte specific microRNA mirl22a into the El A 3 ' UTR. We have also shown that this virus can be delivered at doses above the maximum tolerated dose for Ad5-WT without toxicity.

Here we have shown that Ad5-mirl22 can mediate significant reduction in tumour volume with reduced toxicity in a dose escalation treatment regime. Repeat administration of Ad5-mirl22, at a dose well above the MTD for Ad5-WT, causes tumour reduction and increased survival in all animals when compared with controls. This is the first anti-cancer efficacy reported using a microRNA regulated DNA virus. These data also show that whilst Ad5-WT is a potent virus, the acute hepatic toxicity following intravenous administration limits dose size and therefore hinders anti-cancer efficacy. The use of microRNA to regulate RNA virus replication has been shown to be an efficient mechanism of control in multiple viruses. However, the regulation of a DNA virus could be considered an inefficient mechanism of control because the viral genome is not destroyed. This study has shown that the use of this method to control the expression of an essential viral transcript, in this case Adenovirus ElA, can reduce toxicity dramatically without affecting viral replication in target cells. Moreover, the reduced mutation rate and observed in DNA viruses compared to RNA viruses may prove to be essential for maintenance of the microRNA binding sites in vivo.

Most methods of attenuating virus replication can only be applied to a small subset of viruses. For example, tissue specific promoters can only be used in DNA viruses that replicate in the nucleus. The use of microRNAs to control virus replication can be applied to all virus types because all viruses require mRNA translation in order to replicate. Moreover, many of the major viral pathological sites express tissue specific microRNAs, often at high levels.

Materials and Methods Animal Models

Nu/nu out bred mice were obtained from Charles Rivers Laboratories at 4-6 weeks old. 5x10⁶ HepG2 cells were injected subcutaneously and monitored for tumour growth. Mice were randomised prior to treatment initial tumour sizes were typically. All animals were pre-treated with bisphophonate liposomes (100 μl/mouse) 24h before the first dose of virus in all studies. In the dose escalation study mice received one injection prior to the first dose, hi the repeat administration of Ad-mirl22a study bisphophonate liposomes were administered at day -1 and day 15. Controls also received this treatment.

Tumour sizing and calculation

Tumour volume was measured using hand held callipers and is defined as the size of the largest tumour in each mouse. Smaller peripheral tumours were not included in data Tumour surface area (as presented in figure 12) was determined by calculating the area of an oval. Tumour volume (as presented in figure 13) was calculated as an ellipsoid. Imaging

In vivo virus activity was monitored via live imaging using an IVIS 100 system (Xenogen, MA). D-Luciferin (potassium salt) (Gold Biotechnology inc) was prepared in PBS at 15.8mg/ml. Luciferin was administered via intra-peritoneal injection and allowed to circulate for 4 minutes prior to imaging. Light images were performed on anesthetised animals using a crappy camera.

Adenovirus preparations.

AU adenoviruses were grown in A549 cells, purified by double banding in CsCl gradients with benzonase treatment after the first banding. Viral particle (vp) number was determined by measuring DNA content using a modified version of the PicoGreen assay (Invitrogen, Paisley, UK) [I]. TCID₅₀ calculated with the KARBER statistical method [2] was used to estimate the adenovirus titer (TCID₅₀ units/ml) and corrected to determine plaque forming units/ml (pfu/ml). Adenovirus preparations characteristics are as follows: Ad5 wild type: 1.13 x 10¹² vp/ml, 1.98 x 10¹¹ pfu/ml and particle:infectivity (P:I) ratio of 5.6; Ad5mirl22aX4: 1.29 x 10¹² vp/ml, 2.01 x 10¹¹ pfu/ml and particle:infectivity (P :I) ratio of 6.4. All virus preparations were screened for endotoxin and verified negative prior to use.

Maintenance of cell lines

Human hepatocellular carcinoma HepG2 cells and A549 lung carcinoma cells were obtained from the European Collection of Cell Cultures (Porton Down, UK), and maintained in DMEM with 10% foetal bovine serum (FBS) (PAA Laboratories, Yeovil, UK) including penicillin (25 U/ml) and streptomycin (10 mg/ml).

Measurement of Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)

Blood was taken from mice by cardiac puncture and allowed to clot (15 min, room temperature) and spun at 1200 g for 10 min. Serum was isolated and immediately frozen at -20°C). Samples of thawed serum (5μl) were added to ALT reagent (995 μl, Microgenics) or AST reagent (995μl, Microgenics) in a 1 ml quartz cuvette, incubated at 37⁰C and the change in absorbance (340 nm) per minute was monitored. Units of ALT and AST activity were calculated according to the manufacturer's instructions.

1. Mittereder N, March KL, Trapnell BC (1996) Evaluation of the concentration and bioactivity of adenovirus vectors for gene therapy. J Virol 70: 7498-7509.

2. Karber G (1931) 50% end-point calculation. Arch Exp Pathol Pharmak 162: 480-

483.

Description of the drawings Figure 1. Regulation of transgene expression in vitro using microRNA binding sites. A concatamer of 4 binding sites for mir-122 was incorporated into the 3' UTR of Luciferase under control of a CMV immediate early promoter, and similarly 4 binding sites for mir-122 were incorporated into the 3' UTR of an ElA- Luciferase fusion protein, with transcription regulated by the El A promoter. Both constructs were produced as plasmids and transfected using DOTAP into Huh7 human hepatocellular carcinoma cells (which express mir-122), and into 293 cells (which do not express mir-122). The presence of the mirl22 binding sites had no effect on expression levels in 293 cells, but in Huh7 cells the constructs containing mir-122 binding sites showed significantly lower transgene expression, decreased up to 100-fold compared to non-mir-122 binding site-containing controls. This is consistent with increased degradation of mRNA containing mir-122 binding sites in cells containing mir-122.

Figure 2. Plasmids (as described in Figure 1) (0.8 pmol) were administered to normal mice by hydrodynamic injection into the tail vein. Luciferase levels were measured using an Ivis-100 luminescence camera after 8h. Constructs containing mir-122 binding sites showed dramatically lower levels of Luciferase expression than controls not containing mir-122 binding sites. Simple CMV promoter- Luciferase constructs showed 50 fold lower Luciferase expression when mir-122 binding sites were present, while El A-luciferase fusion protein constructs showed 80-fold less expression when mir-122 binding sites were present.

Figure 3. Plasmids (as described in Figure 1) (0.8pmol) were administered to normal mice by hydrodynamic injection into the tail vein. Luciferase levels were measured using an Ivis-100 luminescence camera after 24h. Constructs containing mir-122 binding sites showed dramatically lower levels of Luciferase expression than controls not containing mir-122 binding sites. Simple CMV promoter- Luciferase constructs showed 57 fold lower Luciferase expression when mir-122 binding sites were present, while El A-luciferase fusion protein constructs showed 21 -fold less expression when mir-122 binding sites were present.

Figure 4. Plasmids (as described in Figure 1) (O.δpmol) were administered to normal mice by hydrodynamic injection into the tail vein. Luciferase levels were measured using an Ivis-100 luminescence camera after 48h. Constructs containing mir-122 binding sites showed dramatically lower levels of Luciferase expression than controls not containing mir-122 binding sites. Simple CMV promoter- Luciferase constructs showed 129 fold lower Luciferase expression when mir-122 binding sites were present, while El A-luciferase fusion protein constructs showed 3- fold less expression when mir-122 binding sites were present. Figure 5. Effects of time on the differential expression of Luciferase constructs containing mir-122 binding sites in vivo. Data shown in Figures 2-4 is summarized and it can be seen that both the simple CMV-driven Luciferase and the El A-luciferase fusion protein show consistent inhibition of expression by the presence of mir-122 binding sites. Figure 6 Plasmid construction. pCIK-Lux (referred to as pCMV-Luc) was cleaved with Notl and concatamers of microRNA122a binding sites (4 or 8 sense, or 4 antisense; the sequence of the 4 sense insert is shown at the bottom of the figure) inserted into the luciferase 3 'UTR. Both pCMV-Luc and the version containing 4 microRNA sites (pCMV-Luc-mirl22aX4) were modified with the C terminal half of ElA expression cassette, isolated from pAd5WT (Ad5 wild type) by PCR. Both resulting constructs were then cloned into pAd5Kpnl, which contains the ElA promoter and coding sequence, to produce ElA promoter regulated El A-luciferase fusion constructs.

Figure 7. Effects of microRNA binding sites on expression of CMV promoter driven luciferase plasmids in vitro. Cells were seeded in triplicate in 12 well plates. After 24 h 0.5μg of plasmid DNA (containing 0 (black), 4 (light grey) or 8 (white) sense microRNA122a binding sites, or 4 antisense binding sites (dark grey)) was mixed with 2.5ul DOTAP (Roche) reagent. 24h following transfection cells were lysed and relative luminescence was measured using 25 μl cell lysate. N=3, Error bars +/- standard deviation and data is shown as RLU/μg cell protein, determined by BCA assay. (** PO.005) Figure 8. Effects of including binding sites for microRNA122a on expression of plasmids in vivo following hydrodynamic delivery to mice. A Imaging luminescence (8h from mice administered pCMV-Luc not containing (left panel) and containing (right panel) four binding sites for microRNA122a (plasmids pCMV- luciferase and pCMV-luciferase-mirl22aX4 in Figure 6). The animal on the right side of all images is a control treated with PBS, but mock injected with luciferin, used to provide a background reading. B: Imaging luminescence (8h from mice administered pEl A-Luc fusion constructs not containing (left panel) and containing (right panel) four binding sites for microRNA122a (plasmids pAd5-Kpnl-El A-Luc and pAd5-Kpnl-El A-luc-rnirl22aX4 in Figure 6). The animal on the right is an untreated control. The two images in A are directly comparable with each other, as also the two images in B; however scaling is different between A and B in order to accommodate substantially different signal intensities from these plasmids. C: Time course of luciferase expression from CMV promoter-driven and ElA promoter driven constructs shown in A and B. Black = 8h, Grey = 24h, White = 48h. n = 4 throughout (except pCMV-mirl22a where n=3), error bars show standard deviation.

Figure 9. Regulation of ElA expression. A. Structures of viruses engineered and used in this study, (i) Ad5 WT (ii) Four tandem repeats of binding sites for microRNA 122a were inserted into the 3' UTR of ElA. (iii) Luciferase coding sequence was inserted into Ad5 to generate a fusion with the ElA coding sequence. (iv) Four tandem repeats of binding sites for microRNA 122a were inserted into 3' UTR of luciferase in the virus shown in iii.

C-E. B. A549 cells were seeded at 5x10⁴ cells per well and transfected with ρre-mirl22 (Ambion) or pre-mir negative control (Ambion). Immediately following transfection Ad-ElA-Luc-mirl22aX4 was added at 10 vp/cell in 450μl DMEM media (10% FCS). 18 h later, 30 pmol/well of pre-cursor mirl22 and negative control precursor microRNAs were added to each well in addition to the 500μl described above. Luciferase readings were performed at 24h. C-E: Time course of luciferase expression of Ad5-El A-Luc (solid squares) and Ad5-El A-Luc-mir (open squares) in microRNA122-negative OVC AR3 (C) and A549 (D) cells, and in microRNA122-positive Huh7 cells (E) in vitro. (*** P<0.0005) Figure 10. Luciferase transgene expression following intravenous administration of reporter viruses to mice in vivo. Groups of four mice were administered intravenously 5x10¹⁰ virus particles of Ad5-E1A-Luc (left hand group of each pair of images) or Ad5-ElA-Luc-mir (right hand group of each pair) and luminescence was quantified using an IvislOO imaging system after 6 - 96h. The mouse on the right of all images is an untreated control, mock injected with luciferin for background levels. Images within pairs can be directly compared, although the scaling is different between time points (see scale bars for details). The graph summarises the expression profile as a function of time.

Figure 11. Assessment of hepatotoxicity of wild type Ad5 modified with microRNA binding sites. A. Measurement of serum ALT (black bars) and AST

(grey bars) 72h following intravenous administration of 5xlO¹⁰ viral particles of wild type Ad5 and Ad5-mirl22aX4. Analysis was performed as described in the Methods section. B. Adenovirus genomes in murine liver were measured by real time PCR 72h following intravenous administration of 5x10¹⁰ viral particles of wild type Ad5 WT and Ad5-mirl22aX4, as described in the Methods section. C Assessment of liver histology. The left liver lobe from each mouse was immersed in 10% buffered formalin overnight at room temperature, embedded in wax and sectioned using a vibratome. Sections were stained with haematoxylin and eosin and analysed by light microscopy at x 40 magnification. Mice were treated with PBS, non-replicating El, E3 -deleted Ad5 expressing GFP (Ad5-GFP), wild type Ad5 or wild type Ad5 modified to contain 4 microRNA122a binding sites, as indicated. (*** P<0.0005) Figure 12. The timeline for the experiment, tumour surface areas and doses. Figure 13. Tumour volumes. 06

hsa-let-7a UQAGGUAGUAQGUUGUAUAGUU mdo-miR-302c UAAGUGCUUCCAUGUUUCAGU hsa-let-7a UGAGGUAGUAGGUUGUAUAGUU mdo-miR-302d UAAGUGCUUCCAUGUUUGAGU hsa-let-7a* CUAUACAAUCUACUGUCUUUC mdo-miR-30a UGUAAACAUCCUCGACUGGAAG hsa-let-7b UGAGGUAGUAGGUUGUGUGGUU mdo-miR-31 GGAGGCAAGAUGUUGGCAUAGCUG hsa-let-7t>* CUAUACAACCUACUGCCUUCCC mdo-miR-32 UAUUGCACAUUACUAAGUUGC hsa-let-7c UGAGGUAGUAGGUUGUAUGGUU mdo-miR-338 UCCAGCAUCAGUGAUUUUGUUGA hsa-let-7c* UAGAGUUACACCCUGGGAGUUA mdo-miR-340 AAGUAAUGAGAUUGAUUUCUGU hsa-let-7d AGAGGUAGUAGGUUGCAUAGUU mdo-miR-34a UGGCAGUGUCUUAGCUGGUUGUU hsa-let-7d* CUAUACGACCUGCUGCCUUUCU mdo-miR-365 UAAUGCCCCUAAAAAUCCUUAU hsa-let-7e UGAGGUAGGAGGUUGUAUAGUU mdo-miR-367 GAAUUGCACUUUAGCAAUGGUGA hsa-let-7e* CUAUACGGCCUCCUAGCUUUCC mdθ-miR-375 UUUUGUUCGUUCGGCUCGCGUGA hsa-let-7f UGAGGUAGUAGAUUGUAUAGUU mdo-raiR-383 AGAUCAGAAGGUGAUUGUGGCU hsa-let-7f-l* CUAUACAAUCUAUUGCCUUCCC mdo-miR-425 AUCGGGAAUAUCGUGUCCGUCC hsa-let-7f-2* CUAUACAGUCUACUGUCUUUCC mdo-miR-449 UGGCAGUGUAUUGUUAGCUGGU hsa-let-7g 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UAAAGUGCUGACAGUGCAGAU mdvl-miR-M2 GUUGUAUUCUGCCCGGUAGUCCG hsa-miR-106b* CCGCACUGUGGGUACUUGCUGC mdvl-miR-M2* CGGACUGCCGCAGAAUAGCUU hsa-πuR-107 AGCAGCAUUGUACAGGGCUAUCA mdvl-miR-M3 AUGAAAAUGUGAAACCUCUCCCGC hsa-miR-lOa UACCCUGUAGAUCCGAAUUUGUG mdvl-miR-M4 UUAAUGCUGUAUCGGAACCCUUC hsa-πuR-lOa* CAAAUUCGUAUCUAGGGGAAUA mdvl-miR-M4* AAUGGUUCUGACAGCAUGACC hsa-miR-10b UACCCUGUAGAACCGAAUUUGUG mdvl-miR-M5 UGUGUAUCGUGGUCGUCUACUGU hsa-miR-10b* ACAGAUUCGAUUCUAGGGGAAU mdvl-miR-M5* AACCGUAUGCGAUCACAUUGAC hsa-miR-1178 UUGCUCACUGUUCUUCCCUAG mdvl-miR-M6 UCUGUUGUUCCGUAGUGUUCUC hsa-miR-1179 AAGCAUUCUUUCAUUGGUUGG mdvl-miR-M6* GAGAUCCCUGCGAAAUGACAGU hsa-miR-1180 UUUCCGGCUCGCGUGGGUGUGU mdvl-miR-M7 UGUUAUCUCGGGGAGAUCCCGAU hsa-miR-1181 CCGUCGCCGCCACCCGAGCCG mdvl-miR-M7* UCGAGAUCUCUACGAGAUUACAG hsa-miR-1182 GAGGGUCUUGGGAGGGAUGUGAC mdvl-miR-M8-3p GUGACCUCUACGGAACAAUAGU hsa-miR-1183 CACUGUAGGUGAUGGUGAGAGUGGGCA mdvl-miR-MS-Sp UAUUGUUCUGUGGUUGGUUUCG hsa-miR-1 184 CCUGCAGCGACUUGAUGGCUUCC mdvl-miR-M9 UUUUCUCCUUCCCCCCGGAGUU hsa-miR-1 185 AGAGGAUACCCUUUGUAUGUU mdvl-miR-M9* AAACUCCGAGGGCAGGAAAAAG hsa-miR-1197 UAGGACACAUGGUCUACUUCU mdv2-miR-M14-3p UCAGGAAGUUCCGUGCCCGAA hsa-miR-1200 CUCCUGAGCCAUUCUGAGCCUC mdv2-miR-M14-5p GUGUGGUACGGUGCACCCUGAGA hsa-miR-1201 AGCCUGAUUAAACACAUGCUCUGA mdv2-miR-M15 UGGUGUGUUUUUCCCUUCCAUCGCA hsa-miR-1202 GUGCCAGCUGCAGUGGGGGAG mdv2-miR-M15* UGGAAGGGAAAGGCAAACCGGA hsa-miR-1203 CCCGGAGCCAGGAUGCAGCUC mdv2-miR-M16 CAUCCAGUCUGUUUUGGCAUCUGA hsa-miR-1204 UCGUGGCCUGGUCUCCAUUAU mdv2-miR-M17 UAGGACAACCGGGACGGACAGG hsa-miR-1205 UCUGCAGGGUUUGCUUUGAG mdv2-miR-M17* AGUCCUUCCCGGGUCCCCUAGA hsa-miR-1206 UGUUCAUGUAGAUGUUUAAGC mdv2-miR-M18-3p CAAUGCCUGCGGAGAGAAAGA hsa-miR-1207-3p UCAGCUGGCCCUCAUUUC mdv2-miR-M18-5p UGUUUUCUCUCAGGCUGGCAUUGC hsa-miR-1207-5p UGGCAGGGAGGCUGGGAGGGG mdv2-raiR-M19 CAUGCCCCCCUCCGAGGGUAGC hsa-miR-1208 UCACUGUUCAGACAGGCGGA mdv2-miR-M20 UCAAGUACUGCGCGCAAGGACCG hsa-miR-122 UGGAGUGUGACAAUGGUGUUUG mdv2-miR-M20* UCCUUAGCGUGGUGCCUGAGA hsa-miR-122* AACGCCAUUAUCACACUAAAUA mdv2-miR-M21 GAGCACCACGCCGAUGGACGGAGA hsa-miR-1224-3p CCCCACCUCCUCUCUCCUCAG mdv2-miR-M21* UCCUCCUUCGCGGGGUGCUUGA hsa-miR-1224-5p GUGAGGACUCGGGAGGUGG mdv2-miR-M22 UCUUACACGCACGUCACUCUGGUC hsa-miR-1225-3p UGAGCCCCUGUGCCGCCCCCAG mdv2-miR-M22* UAGUGGCUUGCUUGUAGGCUGU hsa-miR-1225-5p GUGGGUACGGCCCAGUGGGGGG mdv2-miR-M23 AUGGUCCGUGGUACGGUGUCCU hsa-πuR-1226 UCACCAGCCCUGUGUUCCCUAG mdv2-miR-M24 UUAGAUGCCGUCAGGGAAAGAU hsa-miR-1226* GUGAGGGCAUGCAGGCCUGGAUGGGG mdv2-miR-M25-3p CAUGCACUACUCCGGGGGUAGGAC hsa-miR-1227 CGUGCCACCCUUUUCCCCAG mdv2-miR-M25-5p CCUCCUUCGGACGAGUGCUUGCCG hsa-miR-1228 UCACACCUGCCUCGCCCCCC mdv2-miR-M26 UCCUUUGUGCUGUGUGUGAGA hsa-miR-1228* GUGGGCGGGGGCAGGUGUGUG mdv2-miR-M27-3p GCGUCGAGCACCGUGCUGGAGGAA hsa-miR-1229 CUCUCACCACUGCCCUCCCACAG mdv2-miR-M27-5p CUUCGUCCGGUGUUCGAGGCGU hsa-miR-1231 GUGUCUGGGCGGACAGCUGC mdv2-miR-M28 UUUUCUCGACGCCUACCCUCGGCG hsa-miR-1233 UGAGCCCUGUCCUCCCGCAG mdv2-miR-M28* CGAGGGUAGGCGCAGAGGAAAUCG hsa-miR-1234 UCGGCCUGACCACCCACCCCAC mdv2-miR-M29 UCUUCACGUACCUCUCUAUGGCU hsa-miR-1236 CCUCUUCCCCUUGUCUCUCCAG mdv2-miR-M30 CAACACUCCCUCGGACGCAGCA hsa-miR-1237 UCCUUCUGCUCCGUCCCCCAG mghv-miR-Ml-1 UAGAAAUGGCCGUACUUCCUUU hsa-miR-1238 CUUCCUCGUCUGUCUGCCCC mghv-miR Ml-2 CAGACCCCCUCUCCCCCUCUUU hsa-miR-124 UAAGGCACGCGGUGAAUGCC mghv-miR-Ml-3 GAGGUGAGCAGGAGUUGCGCUU bsa-miR-124* CGUGUUCACAGCGGACCUUGAU mghv-miR-Ml-4 UCGAGGAGCACGUGUUAUUCUA hsa-miR-1243 AACUGGAUCAAUUAUAGGAGUG mghv-miR-Ml-5 AGAGUUGAGAUCGGGUCGUCUC hsa-miR-1244 AAGUAGUUGGUUUGUAUGAGAUGGUU mghv-miR-Ml-6 UGAAACUGUGUGAGGUGGUUUU hsa-miR-1245 AAGUGAUCUAAAGGCCUACAU mghv-miR-Ml-7-3p GAUAUCGCGCCCACCUUUAUU hsa-miR-1246 AAUGGAUUUUUGGAGCAGG mghv-miR-M 1 -7-5p AAAGGUGGAGGUGCGGUAACCU hsa-miR-1247 ACCCGUCCCGUUCGUCCCCGGA mghv-nuR-Ml-8 AGCACUCACUGGGGGUUUGGUC hsa-miR-1248 ACCUUCUUGUAUAAGCACUGUGCUAAA mghv-miR-Ml-9 UCACAUUUGCCUGGACCUUUUU hsa-miR-1249 ACGCCCUUCCCCCCCUUCUUCA mml-let-7a UGAGGUAGUAGGUUGUAUAGUU hsa-miR-1250 ACGGUGCUGGAUGUGGCCUUU mml-lεt-7b UGAGGUAGUAGGUUGUGUGGUU hsa-miR-1251 ACUCUAGCUGCCAAAGGCGCU mml-let-7c UGAGGUAGUAGGUUGUAUGGUU hsa-miR-1252 AGAAGGAAAUUGAAUTJCAUUUA πunl-let-7d AGAGGUAGUAGGUUGCAUAGUU hsa-miR-1253 AGAGAAGAAGAUCAGCCUGCA πunl-let-7e UGAGGUAGGAGGUUGUAUAGUU hsa-miR-1254 AGCCUGGAAGCUGGAGCCUGCAGU πunl-let-7f UGAGGUAGUAGAUUGUAUAGUU hsa-miR-1255a AGGAUGAGCAAAGAAAGUAGAUU mml-let-7g UGAGGUAGUAGUUUGUACAGUU hsa-miR-1255b CGGAUGAGCAAAGAAAGUGGUU mml-let-7i UGAGGUAGUAGUUUGUGCUGUU hsa-miR-1256 AGGCAUUGACUUCUCACUAGCU mml-miR-1 UGGAAUGUAAAGAAGUAUGUAU hsa-miR-1257 AGUGAAUGAUGGGUUCUGACC πunl-miR-100 AACCCGUAGAUCCGAACUUGUG hsa-miR-1258 AGUUAGGAUUAGGUCGUGGAA mml-miR-101 UACAGUACUGUGAUAACUGAAG hsa-miR-1259 AUAUAUGAUGACUUAGCUUUU mml-miR-103 AGCAGCAUUGUACAGGGCUAUGA hsa-miR-12Sa-3p ACAGGUGAGGUUCUUGGGAGCC mml-miR-105 UCAAAUGCUCAGACUCCUGUGGU hsa-miR-125a-5p UCCCUGAGACCCUUUAACCUGUGA mml-miR-106a AAAAGUGCUUACAGUGCAGGUAGC hsa-miR- 125b UCCCUGAGACCCUAACUUGUGA mmI-miR-106b UAAAGUGCUGACAGUGCAGAU hsa-miR-12Sb-l* ACGGGUUAGGCUCUUGGGAGCU mmI-miR-107 AGCAGCAUUGUACAGGGCUAUCA hsa-miR-125b-2* UCACAAGUCAGGCUCUUGGGAC mml-miR-lOa UACCCUGUAGAUCCGAAUUUGUG hsa-miR-126 UCGUACCGUGAGUAAUAAUGCG mml-miR-10b UACCCUGUAGAACCGAAUUUGUG hsa-miR- 126* CAUUAUUACUUUUGGUACGCG mml-miR-1224 GUGAGGACUCGGGAGGUC3G hsa-miR-1260 AUCCCACCUCUGCCACCA mml-miR-1224* CCCCACCUCCUCUCUCCUCAG hsa-miR-1261 AUGGAUAAGGCUUUGGCUU mml-miR-1225-3p CUGAGCCCCUGUGCCGCCCCCAG hsa-miR-1262 AUGGGUGAAUUUGUAGAAGGAU mml-miR-1225-5p GUGGGUACGGCCCAGUGGGGG hsa-miR-1263 AUGGUACCCUGGCAUACUGAGU mml-miR-1226 UCACCAGCCCUGUGUUCCCUAG hsa-miR-1264 CAAGUCUUAUUUGAGCACCUGUU imnl-miR-1227 GUGGGGCCAGGCGGUGGUGG hsa-miR-1265 CAGGAUGUGGUCAAGUGUUGUU mml-miR-122a UGGAGUGUGACAAUGGUGUUUG hsa-miR-1266 CCUCAGGGCUGUAGAACAGGGCU mml-miR-1230 GUGGGUGGGGGCAUCUCGGA hsa-miR-1267 CCUGUUGAAGUGUAAUCCCCA mml-miR-1232 CUGACCCCGACCACCCCGCAG hsa-miR-1268 CGGGCGUGGUGGUGGGGG mml-miR-1235 UCUAACCGCACCGUCCCCCAG hsa-miR-1269 CUGGACUGAGCCGUGCUACUGG mml-miR-1239 UUCCCCAUUCUGCCUGGCCUAG hsa-raiR-1270 CUGGAGAUAUGGAAGAGCUGUGU mml-miR-1240 UCACCAUGACCCUGAUCCCACU hsa-miR-1271 CUUGGCACCUAGCAAGCACUCA mml-miR-1241 CUCACCUCUCUGUGCCUUCCAG hsa-miR-1272 GAUGAUGAUGGCAGCAAAUUCUGAAA mml-miR-124a UUAAGGCACGCGGUGAAUGCCA hsa-miR-1273 GGGCGACAAAGCAAGACUCUUUCUU mml-miR-125a-3p ACAGGUGAGGUUCUUGGGAGCC hsa-miR-127-3p UCGGAUCCGUCUGAGCUUGGCU mml-miR-125a-5p UCCCUGAGACCCUUUAACCUGUGA hsa-miR-1274a GUCCCUGUUCAGGCGCCA mml-miR-125b UCCCUGAGACCCUAACUUGUGA hsa-miR-1274b UCCCUGUUCGGGCGCCA mml-miR-126 UCGUACCGUGAGUAAUAAUGCG hsa-miR-1275 GUGGGGGAGAGGCUGUC mml-miR-127 UCGGAUCCGUCUGAGCUUGGCU hsa-miR-127-5p CUGAAGCUCAGAGGGCUCUGAU mml-miR-128a UCACAGUGAACCGGUCUCUUUU hsa-miR-1276 UAAAGAGCCCUGUGGAGACA mml-miR-128b UCACAGUGAACCGGUCUCUUU hsa-miR-1277 UACGUAGAUAUAUAUGUAUUUU mml-miR-129-3p AAGCCCUUACCCCAAAAAGUAU hsa-miR-1278 UAGUACUGUGCAUAUCAUCUAU mml-πuR-129-5p CUUUUUGCGGUCUGGGCUUGC hsa-miR-1279 UCAUAUUGCUUCUUUCU mml-miR-130a CAGUGCAAUGUUAAAAGGGC hsa-miR-12S UCACAGUGAACCGGUCUCUUU mml-miR-130b CAGUGCAAUGAUGAAAGGGCAU hsa-miR-1280 UCCCACCGCUGCCACCC mml-miR-132 UAACAGUCUACAGCCAUGGUCG hsa-miR-1281 UCGCCUCCUCCUCUCCC mml-miR-133a UUGUCCCCUUCAACCAGCUGU hsa-miR-1282 UCGUUUGCCUUUUUCUGCUU mml-miR-133b UUUGGUCCCCUUCAACCAGCUA hsa-miR- 1283 UCUACAAAGGAAAGCGCUUUCU mml-miR-133c UUUGGUCCCCUUCAACCAGCUG hsa-miR-1284 UCUAUACAGACCCUGGCUUXΛJC mml-miR-134 UGUGACUGGUUGACCAGAGGGG hsa-miR-1285 UCUGGGCAACAAAGUGAGACCU mml-miR-135a UAUGGCUUUUUAUUCCUAUGUGA hsa-miR-1286 UGCAGGACCAAGAUGAGCCCU mml-miR-135b UAUGGCUUUUCAUUCCUAUGUGA hsa-miR-1287 UGCUGGAUCAGUGGUUCGAGUC mml-miR-136 ACUCCAUUUGUUUUGAUGAUGGA hsa-miR-1288 UGGACUGCCCUGAUCUGGAGA mml-miR-137 UUAUUGCUUAAGAAUACGCGUAG hsa-miR-1289 UGGAGUCCAGGAAUCUGCAUUUU mml-miR-138 AGCUGGUGUUGUGAAUCAGGCCG hsa-miR-129* AAGCCCUUACCCCAAAAAGUAU mml-miR-139-3p GGAGACGCGGCCCUGUUGGAGU hsa-miR-1290 UGGAUUUUUGGAUCAGGGA mml-miR-139-5p UCUACAGUGCACGUGUCUCCAG hsa-miR-1291 UGGCCCUGACUGAAGACCAGCAGU mml-πuR-140-3p UACCACAGGGUAGAACCACGG hsa-miR- 1292 UGGGAACGGGUUCCGGCAGACGCUG mml-miR-140-5p CAGUGGUUUUACCCUAUGGUAG hsa-miR-1293 UGGGUGGUCUGGAGAUUUGUGC mml-miR-141 AACACUGUCUGGUAAAGAUGG hsa-miR-129-3p AAGCCCUUACCCCAAAAAGCAU mml-miR-142-3p UGUAGUGUUUCCUACUUUAUGGA hsa-miR-1294 UGUGAGGUUGGCAUUGUUGUCU mml-miR-142-5p CAUAAAGUAGAAAGCACUACU hsa-miR-1295 UUAGGCCGCAGAUCUGGGUGA mml-miR-143 UGAGAUGAAGCACUGUAGCUC hsa-miR-129-5p CUUUUUGCGGUCUGGGCUUGC mml-miR-144 UACAGUAUAGAUGAUGUACU hsa-miR-1296 UUAGGGCCCUGGCUCCAUCUCC mml-miR-145 GUCCAGUUUUCCCAGGAAUCCCUU hsa-miR-1297 UUCAAGUAAUUCAGGUG mml-miR-146a UGAGAACUGAAUUCCAUGGGUU hsa-miR-1298 UUCAUUCGGCUGUCCAGAUGUA mml-miR-146b-3p UGCCCUGUGGACUCAGUUCUGG hsa-miR-1299 UUCUGGAAUUCUGUGUGAGGGA mml-miR- 146b-5p UGAGAACUGAAUUCCAUAGGCU hsa-miR-1300 UUGAGAAGGAGGCUGCUG mml-miR-147a GUGUGUGGAAAUGCUUCUGCUA hsa-miR-1301 UUGCAGCUGCCUGGGAGUGACUUC mml-miR- 147b GUGUGCGGAAGUGCUUCUGCU hsa-miR-1302 UUGGGACAUACUUAUGCUAAA mml-miR- 148a UCAGUGCACUACAGAACUUUGU hsa-miR-1303 UUUAGAGACGGGGUCUUGCUCU mml-miR-148b UCAGUGCAUCACAGAACUUUGU hsa-miR-1304 UUUGAGGCUACAGUGAGAUGUG mml-miR- 149 UCUGGCUCCGUGUCUUCACUCCC hsa-miR-1305 UUUUCAACUCUAAUGGGAGAGA mml-miR-150 UCUCCCAACCCUUGUACCAGUG hsa-miR-1306 ACGUUGGCUCUGGUGGUG mml-miR- 151 ~3p CUAGACUGAAGCUCCUUGAGG hsa miR-1307 ACUCGGCGUGGCGUCGGUCGUG mml-miR- 151 -5p UCGAGGAGCUCACAGUCUAGU hsa miR-1308 GCAUGGGUGGUUCAGUGG mml-miR-152 UCAGUGCAUGACAGAACUUGG hsa-miR-130a CAGUGCAAUGUUAAAAGGGCAU mml-miR-153 UUGCAUAGUCACAAAAGUGA hsa-miR-130a* UUCACAUUGUGCUACUGUCUGC mml-miR-154 UAGGUUAUCCGUGUUGCCUUCG hsa-miR-130b CAGUGCAAUGAUGAAAGGGCAU mml-miR-155 UUAAUGCUAAUCGUGAUAGGGGU hsa-miR-130b* ACUCUUUCCCUGUUGCACUAC mml iraR 15a UAGCAGCACAUAAUGGUUUGUG hsa-miR-132 UAACAGUCUACAGCCAUGGUCG mml-miR-lSb UAGCAGCACAUCAUGGUUUACA hsa miR-132* ACCGUGGCUUUCGAUUGUUACU mral-miR-16 UAGCAGCACGUAAAUAUUGGCG hsa-tniR-1321 CAGGGAGGUGAAUGUGAU mml-miR-17-3p ACUGCAGUGAAGGCACUUGU hsa-miR-1322 GAUGAUGCUGCUGAUGCUG mml-miR-17-5p CAAAGUGCUUACAGUGCAGGUAGU hsa-miR-1323 UCAAAACUGAGGGGCAUUUUCU mml-miR-18 UAAGGUGCAUCUAGUGCAGAUA hsa-miR-1324 CCAGACAGAAUUCUAUGCACUUUC mml-miR-181a AACAUUCAACGCUGUCGGUGAGU hsa-πuR-133a UUUGGUCCCCUUCAACCAGCUG mml miR 181a* ACCAUCGACCGUUGAUUGUACC hsa-miR-133b UUUGGUCCCCUUCAACCAGCUA mml-miR-181b AACAUUCAUUGCUGUCGGUGGGUU hsa-miR 134 UGUGACUGGUUGACCAGAGGGG nunl-miR-181o AACAUUCAACCUGUCGGUGAGU hsa-miR-135a UAUGGCUUUUUAUUCCUAUGUGA mml-miR-181d AACAUUCAUUGUUGUCGGUGGGU hsa-miR-135a* UAUAGGGAUUGGAQCCGUGGCG mml-miR-182 UUUGGCAAUGGUAGAACUCACA hsa-miR-135b UAUGGCUUUUCAUUCCUAUGUGA mml-miR-183 UAUGGCACUGGUAGAAUUCACUG hsa-miR-135b* AUGUAGGGCUAAAAGCCAUGGG mml miR 184 UGGACGGAGAACUGAUAAGGGU hsa-πuR-136 ACUCCAUUUGUUUUGAUGAUGGA mml miR-185 UGGAGAGAAAGGCAGUUCCUGA hsa-miR-136* CAUCAUCGUCUCAAAUGAGUCU mml miR-186 CAAAGAAUUCUCCUUUUGGGCU hsa-πuR-137 UUAUUGCUUAAGAAUACGCGUAG mml-miR-187 UCGUGUCUUGUGUUGCAGCCGG hsa miR-138 AGCUGGUGUUGUGAAUCAGGCCG mml-miR-188 CAUCCCUUGCAUGGUGGAGGGU hsa-miR-138-1* GCUACUUCACAACACCAGGGCC mml-miR-189 GUGCCUACUGAGCUGAUAUCAGU hsa-miR-138-2* GCUAUUUCACGACACCAGGGUU mml-miR- 18b UAAGGUGCAUCUAGUGC AGUUAG hsa-miR-139-3p GGAGACGCGGCCCUGUUGGAGU mml-miR-190a UGAUAUGUUUGAUAUAUUAGGU hsa-miR-139-Sp UCUACAGUGCACGUGUCUCCAG mml-miR-190b UGAUAUGUUUGAUAUUGGGUU hsa-πuR- 140-3p UACCACAGGGUAGAACCACGG mml-miR-191 CAACGGAAUCCCAAAAGCAGCUG hsa-miR-140-5p CAGUGGUUUUACCCUAUGGUAG mml-miR 192 CUGACCUAUGAAUUGACAGCC hsa miR 141 UAACACUGUCUGGUAAAGAUGG mml-miR-193a-3p AACUGGCCUACAAAGUCCCAGU hsa miR 141 * CAUCUUCCAGUACAGUGUUGGA mml-miR-193a-5p UGGGUCUUUGCGGGCGAGAUGA hsa miR 142 3p UGUAGUGUUUCCUACUUUAUGGA mml-miR-193b AACUGGCCCUCAAAGUCCCGCU hsa miR 142-5p CAUAAAGUAGAAAGCACUACU mml-miR-194 UGUAACAGCAACUCCAUGUGGA hsa miR-143 UGAGAUGAAGCACUGUAGCUC mml-miR-195 UAGCAGCACAGAAAUAUUGGC hsa-πuR-143* GGUGCAGUGCUGCAUCUCUGGU mml-miR-196a UAGGUAGUUUCAUGUUGUUGG hsa-miR-144 UACAGUAUAGAUGAUGUACU mml-miR-196b UAGGUAGUUUCCUGUUGUUGGG hsa-miR-144* GGAUAUCAUCAUAUACUGUAAG mml-miR-197 UUCACCACCUUCUCCACCCAGC hsa-miR-145 GUCCAGUUUUCCCAGGAAUCCCU mml-miR-19S GGUCCAGAGGGGAAAUAGG hsa miR 145* GGAUUCCUGGAAAUACUGUUCU mml-miR-199a CCCAGUGUUCAGACUACCUGUUC hsa-miR-146a UGAG AACUGAAUUCC AUGGGUU mml-miR-199a-3p ACAGUAGUCUGCACAUUGGUUA hsa-miR-146a* CCUCUGAAAUUCAGUUCUUCAG mml-miR-199a-5p CCCAGUGUUCAGACUACCUGUUC hsa-miR-146b-3p UGCCCUGUGGACUCAGUUCUGG mml-miR-19a UGUGCAAAUCUAUGCAAAACUGA hsa-miR-146b-5p UGAGAACUGAAUUCCAUAGGCU mml-miR-19b UGUGC AAAUCC AUGC AAAACUGA hsa-miR-147 GUGUGUGGAAAUGCUUCUGC mml-miR 200a UAACACUGUCUGGUAACGAUGU hsa-miR-147b GUGUGCGGAAAUGCUUCUGCUA mml-miR-200c AAUACUGCCGGGUAAUGAUGGA hsa-miR-148a UCAGUGCACUACAGAACUUUGU mml-miR-203 GUGAAAUGUUUAGGACCACUAG hsa-πuR-148a* AAAGUUCUGAGACACUCCGACU mml-miR-204 UUCCCUUUGUCAUCCUAUGCCU hsa-miR-148b UCAGUGCAUCACAGAACUUUGU mml-miR-205 UCCUUCAUUCCACCGGAGUCUG hsa-miR-148b* AAGUUCUGUUAUACACUCAGGC mml-miR-206 UGGAAUGUAAGGAAGUGUGUGG hsa-miR-149 UCUGGCUCCGUGUCUUCACUCCC mml-miR-208a AUAAGACGAGCAAAAAGCUUGU hsa-miR-149* AGGGAGGGACGQGGGCUGUGC mmI-miR-208b AUAAGACGAACAAAAGGUUUGU hsa-miR- 150 UCUCCCAACCCUUGUACCAGUG mml-miR 20a UAAAGUGCUUAUAGUGCAGGUA hsa-miR-150* CUGGUACAGGCCUGGGGGACAG mml-miR-20b CAAAGUGCUCAUAGUGCAGGUAG hsa-miR-151-3p CUAGACUGAAGCUCCUUGAGG mml-miR 21 UAGCUUAUCAGACUGAUGUUGA hsa miR 151 5p UCGAGGAGCUCACAGUCUAGU mml-miR-210 CUGUGCGUGUGACAGCGGCUGA hsa-miR-152 UCAGUGCAUGACAGAACUUGG mml-miR 211 UUCCCUUUGUCAUCCUUUGCCU hsa-miR-153 UUGCAUAGUCACAAAAGUGAUC mml miR 212 UAACAGUCUCCAGUCAGGGCC hsa-miR-154 UAGGUUAUCCGUGUUGCCUUCG mml miR-214 ACAGCAGGCACAGACAGGCAG hsa-miR-154* AAUCAUACACGGUUGACCUAUU mml-miR-215 AUGACCUAUG AAUUGACAG AC hsa-miR-155 UUAAUGCUAAUCGUGAUAGGGGU mml-miR-216a UAAUCUC AGCUGGC AACUGUG A hsa-miR-155* CUCCUACAUAUUAGCAUUAACA mml miR 216b AAAUCUCUGC AGGC AAAUGUGA hsa-miR-15a UAGCAGCACAUAAUGGUUUGUG mml-miR-217 UUCUGC AUCAGGAACUGAUUGGA hsa miR 15a* CAGGCCAUAUUGUGCUGCCUCA mml-miR-218 UUGUGCUUG AUCU AACC AUGU hsa-miR-15b UAGCAGCACAUCAUGGUUUACA mml-miR-219 UGAUUGUCC AAACGC AAUUCU hsa-miR-15b* CGAAUCAUUAUUUGCUGCUCUA mml-miR-219-3p AGAAUUGUGGCUGGACAUCUGU hsa-miR-16 UAGCAGCACGUAAAUAUUGGCG mml-miR-219-5p UGAUUGUCC AAACGC AAUUCU hsa-miR-16-1* CCAGUAUUAACUGUGCUGCUGA mml-miR-22 AAGCUGCCAGUUGAAGAACUGU hsa-miR-16-2* CCAAUAUUACUGUGCUGCUUUA mml-miR-220a CCACCACCAUGUCUGACACUUU hsa iraR 17 CAAAGUGCUUACAGUGCAGGUAG mml miR-220b CCACCACCGUGUCCGACACCU hsa-miR 17* ACUGCAGUGAAGGCACUUGUAG mml-miR-220c CCACCACUGUGUCUGACACCUU hsa miR 181a AACAUUCAACGCUGUCGGUGAGU mml-miR-220d CCACCACCGUGUCUGACACCUU hsa-miR-181a* ACCAUCGACCGUUGAUUGUACC mml-miR-22-1 AGCUACAUUGUCUGCUGGGUUUC hsa-miR-lgla-2* ACCACUGACCGUUGACUGUACC mml-miR-222 AGCUACAUCUGGCUACUCGGU hsa-miR-181b AACAUUCAUUGCUGUCGGUGGGU mml-miR-223 UGUCAGUUUGUCAAAUACCCC hsa-miR-181c AACAUUCAACCUGUCGGUGAGU mml-miR-224 CAAGUCACUAGUGGUUCCGUUUA hsa-miR-1 SIc* AACCAUCGACCGUUGAGUGGAC mml-miR-23a AUCACAUUGCCAGGGAUUUCC hsa-miR-181d AACAUUCAUUGUUGUCGGUGGGU mml-miR-23b AUCACAUUGCCAGGGAUUACC hsa-miR-182 UUUGGCAAUGGUAGAACUCACACU mml-miR-24 UGGCUCAGUUCAGCAGGAACAG hsa-miR-182* UGGUUCUAGACUUGCCAACUA mmI-miR-25 CAUUGCACUUGUCUCGGUCUGA hsa-miR-1825 UCCAGUGCCCUCCUCUCC mml-miR-26a UUCAAGUAAUCCAGGAUAGGCU hsa-miR-1826 AUUGAUCAUCGACACUUCGAACGCAAU mml-miR-26b UUCAAGUAAUUCAGGAUAGGU hsa-miR-1827 UGAGGCAGUAGAUUGAAU mml-miR-27a UUCACAGUGGCUAAGUUCCGCC hsa-miR-183 UAUGGCACUGGUAGAAUUCACU mml-miR-27b UUCACAGUGGCUAAGUUCUGC hsa-miR-183* GUGAAUUACCGAAGGGCCAUAA mml-miR-28 AAGGAGCUCACAGUCUAUUGAG hsa-miR-184 UGGACGGAGAACUGAUAAGGGU mml-miR-296-3p GAGGGUUGGGUGGAGGCUCUCC hsa-miR-185 UGGAGAGAAAGGCAGUUCCUGA raml-miR-296-5p AGGGCCCCCCCUCAAUCCUGU hsa-miR-185* AGGGGCUGGCUUUCCUCUGGUC mml-miR-297 AUGUAUGUGUGCAUGUGCAU hsa-miR-186 CAAAGAAUUCUCCUUUUGGGCU mml-miR-298 AGCAGAAGCCGGGUGGUUCUCCCA hsa-miR-186* GCCCAAAGGUGAAUUUUUUGGG mml-miR-299-3p UAUGUGGGACGGUAAACCGCUU hsa-miR-187 UCGUGUCUUGUGUUGCAGCCGG mml-miR-299-5p UGGUUUACCGUCCCACAUACAU hsa-miR-187* GGCUACAACACAGGACCCGGGC mml-miR-29a CUAGCACCAUCUGAAAUCGGUU hsa-miR-188-3p CUCCCACAUGCAGGGUUUGCA mml-miR-29b UAGCACCAUUUGAAAUCAGUGUU hsa-miR-188-5p CAUCCCUUGCAUGGUGGAGGG mml-miR-29c UAGCACCAUUUGAAAUCGGUUA hsa-miR-18a UAAGGUGCAUCUAGUGCAGAUAG mml-miR-301a CAGUGCAAUAGUAUUGUCAAAGC hsa-miR-18a* ACUGCCCUAAGUGCUCCUUCUGG mml-miR-301b CAGUGCAAUGAUAUUGUCAAAGC hsa-miR-18b UAAGGUGCAUCUAGUGCAGUUAG πraJ-miR-302a UAAGUGCUUCCAUGUUUUGGUGA hsa-miR-18b* UGCCCUAAAUGCCCCUUCUGGC mml-miR-302b UAAGUGCUUCCAUGUUUUAGUAG hsa-miR-190 UGAUAUGUUUGAUAUAUUAGGU mml-miR-302c UAAGUGCUUCCAUGUUUCAGUGG hsa-miR-190b UGAUAUGUUUGAUAUUGGGUU mml-miR-3D2d UAAGUGCUUCCAUGUUUGAGUGU hsa-miR-191 CAACGGAAUCCCAAAAGCAGCUG mml-miR-30a-3p CUUUCAGUCGGAUGUUUGCAGC hsa-miR-191* GCUGCGCUUGGAUUUCGUCCCC mml-miR-30a-5p UGUAAACAUCCUCGACUGGAAG hsa-miR-192 CUGACCUAUGAAUUGACAGCC mmI-miR-30b UGUAAACAUCCUACACUCAGC hsa-miR-192* CUGCCAAUUCCAUAGGUCACAG mml-miR-30c UGUAAACAUCCUACACUCUCAGC hsa-miR-193a-3p AACUGGCCUACAAAGUCCCAGU mml-πiiR-30d UGUAAACAUCCCCGACUGGAAG hsa-miR-193a-5p UGGGUCUUUGCGGGCGAGAUGA mml-miR-30e UGUAAACAUCCUUGACUGGAAG hsa-miR-193b AACUGGCCCUCAAAGUCCCGCU mml-miR-31 GGCAAGAUGCUGGCAUAGCUG hsa-miR-193b* CGGGGUUUUGAGGGCGAGAUGA mml-miR-32 UAUUGCACAUUACUAAGUUGC hsa-miR-194 UGUAACAGCAACUCCAUGUGGA mml-miR-320 AAAAGCUGGGUUGAGAGGGCGA hsa-πuR-194* CCAGUGGGGCUGCUGUUAUCUG mml-πiiR-323-3p CACAUUACACGGUCGACCUCU hsa-miR-195 UAGCAGCACAGAAAUAUUGGC mml-miR-323-5p AGGUGGUCCGUGGCGCGUUCGC hsa-miR-195* CCAAUAUUGGCUGUGCUGCUCC mml-miR-324-3p ACUGCCCCAGGUGCUGCUGG hsa-miR-196a UAGGUAGUUUCAUGUUGUUGGG mml-miR-324-5p CGCAUCCCCUAGGGCAUUGGUGU hsa-miR-196a* CGGCAACAAGAAACUGCCUGAG mml-miR-325 CCUAGUAGGUGUCCAGUAAGUGU hsa-miR-196b UAGGUAGUUUCCUGUUGUUGGG mml-miR-329 AACACACCUGGUUAACCUCUUU hsa-miR-197 UUCACCACCUUCUCCACCCAGC mml-miR-330-3p GCAAAGCACACGGCCUGCAGAGA hsa-miR-198 GGUCCAGAGGGGAGAUAGGUUC mml-miR-330-Sp UCUCUGGGCCUGUGUCUUAGGC hsa-miR-199a-3p ACAGUAGUCUGCACAUUGGUUA mml-miR-331-3p GCCCCUGGGCCUAUCCUAGAA hsa-miR-199a-5p CCCAGUGUUCAGACUACCUGUUC mml-miR-331-Sp CUAGGUAUGGUCCCAGGGAUCC hsa-miR-199b-3p ACAGUAGUCUGCACAUUGGUUA mml miR 335 UCAAGAGCAAUAACGAAAAAUGU hsa-miR-199b-5p CCCAGUGUUUAGACUAUCUGUUC mml-miR-337-3p CUCCUAUAUGAUGCCUUUCUUC hsa-miR-19a UGUGCAAAUCUAUGCAAAACUGA mml-miR-337-5p GAACGGCUUCAUACAGGAGUU hsa-miR-19a* AGUUUUGCAUAGUUGCACUACA mml-miR-338-3p UCCAGCAUCAGUGAUUUUGUUG hsa-miR-19b UGUGCAAAUCCAUGCAAAACUGA mml-miR-338-5p AACAAUAUCCUGGUGCUGAGUG hsa-miR-19b-l* AGUUUUGCAGGUUUGCAUCCAGC mml-miR-339-3p UGAGCGCCUCGACGACAGAGCCG hsa-miR-19b-2* AGUUUUGCAGGUUUGCAUUUCA mml-miR-339-5p UCCCUGUCCUCCAGGAGCUCACG hsa-miR-200a UAACACUGUCUGGUAACGAUGU mml-miR-33a GUGCAUUGUAGUUGCAUUG hsa-miR-200a* CAUCUUACCGGACAGUGCUGGA mml-miR-33b GUGCAUUGCUGUUGCAUUGC hsa-tniR-200b UAAUACUGCCUGGUAAUGAUGA mml-miR-340 UUAUAAAGCAAUGAGACUGAUU hsa-miR-200b* CAUCUUACUGGGCAGCAUUGGA mmI-miR-342-3p UCUCACACAGAAAUCGCACCCGU hsa-miR-200c UAAUACUGCCGGGUAAUGAUGGA mml-miR-342-5p AGGGGUGCUAUCUGUGAUUGA hsa-miR-200o* CGUCUUACCCAGCAGUGUUUGG mml-miR-345 GCUGACUCCUAGUCAAGGGCUC hsa-miR-202 AGAGGUAUAGGGCAUGGGAA mml-miR-346 UGUCUGCCCGCAUGCCUGCCUCU hsa-miR-202* UUCCUAUGCAUAUACUUCUUUG mml-miR-34a UGGCAGUGUCUUAGCUGGUUGU hsa-miR-203 GUGAAAUGUUUAGGACCACUAG mml-miR-34b CAAUCACUAACUCCACUGCCAU hsa-miR-204 UUCCCUUUGUCAUCCUAUGCCU mml-miR-34o-3p AAUCACUAACCACACGGCCAGG hsa-miR-205 UCCUUCAUUCCACCGGAGUCUG mml-miR-34o-5p AGGCAGUGUAGUUAGCUGAUUGC hsa-miR-206 UGGAAUGUAAGGAAGUGUGUGG mml-miR-361-3p UCCCCCAGGUGUGAUUCUGAUUU hsa-miR-208a AUAAGACGAGCAAAAAGCUUGU mml-miR-361-5p UUAUCAGAAUCUCCAGGGGUAC hsa-miR-208b AUAAGACGAACAAAAGGUUUGU mml-miR-362-3p AACACACCUAUUCAAGGAUUCA hsa-miR-20a UAAAGUGCUUAUAGUGCAGGUAG mml-miR-362-5p AAUCCUUGGAACCUAGGUGUGAGU hsa-miR-20a* ACUGCAUUAUGAGCACUUAAAG mml-raiR-363 AAUUGCACGGUAUCCAUCUGUA hsa-miR-20b CAAAGUGCUCAUAGUGCAGGUAG mml-miR-365 UAAUGCCCCUAAAAAUCCUUAU hsa-miR-20b* ACUGUAGUAUGGGCACUUCCAG iranl-miR-367 AAUUGCACUUUAGCAAUGGUGA hsa-miR-21 UAGCUUAUCAGACUGAUGUUGA mml-miR-369-3p AAUAAUACAUGGUUGAUCUUU hsa-miR-21* CAACACCAGUCGAUGGGCUGU minl-miR-369-5p AGAUCGACCGUGUUAUAUUCGC hsa-miR-210 CUGUGCGUGUGACAGCGGCUGA mml-miR-370 GCCUGCUGGGGUGGAACCUGGU hsa-miR-211 UUCCCUUUGUCAUCCUUCGCCU mml-miR-371-3p AAGUGCCGCCAUGUUUUGAGUGU hsa-miR-212 UAACAGUCUCCAGUCACGGCC mml-miR-371-5p ACUCAAACUGUGGGGGCACU hsa-miR-214 ACAGCAGGCACAGACAGGCAGU mmI-miR-372 AAAGUGCUGCGACAUUUGAGCGU hsa-miR-214* UGCCUGUCUACACUUGCUGUGC mml-miR-373 GAAGUGCUUCGAUUUUGGGGUGU hsa-miR-215 AUGACCUAUGAAUUGACAGAC mml-miR-374a UUAUAAUACAACCUGAUAAGUG hsa-miR-216a UAAUCUCAGCUGGCAACUGUGA mml-miR-374b AUAUAAUACAACCUGCUAAGUG hsa-miR-216b AAAUCUCUGCAGGCAAAUGUGA mml-miR-375 UUUGUUCGUUCGGCUCGCGUGA hsa-miR-217 UACUGCAUCAGGAACUGAUUGGA mml-miR-376a AUCAUAGAGGAAAAUCCACGU hsa-miR-218 UUGUGCUUGAUCUAACCAUGU mml-miR-376b AUCAUAGAGGAAAAUCCAUGUU hsa-miR-218-1* AUGGUUCCGUCAAGCACCAUGG mml-miR-376c AACAUAGAGGAAAUUCCACGU hsa-miR-218-2* CAUGGUUCUGUCAAGCACCGCG mml-miR-377 AUCACACAAAGGCAACUUUUGU hsa-miR-219-l-3p AGAGUUGAGUCUGGACGUCCCG mml-miR-378 ACUGGACUUGGAGUCAGAAGG hsa-miR-219-2-3p AGAAUUGUGGCUGGACAUCUGU mmI-miR-379 UGGUAGACUAUGGAACGUAGG hsa-nuR-219-5p UGAUUGUCCAAACGCAAUUCU mml-πuR-380 UAUGUAAUAUGGUCCACGUCUU hsa-miR-22 AAGCUGCCAGUUGAAGAACUGU mml-πuR-381 UAUACAAGGGCAAGCUCUCUGU hsa-miR-22* AGUUCUUCAGUGGCAAGCUUUA mml-miR-382 GAAGUUGUUCGUGGUGGAUUCG hsa-miR-220a CCACACCGUAUCUGACACUUU mml-miR-383 AGAUCAGAAGGUGAUUGUGGCU hsa-miR-220b CCACCACCGUGUCUGACACUU mml-miR-384 AUUCCUAGAAAUUGUUCAUA hsa-miR-220c ACACAQGGCUGUUGUGAAGACU mml-raiR-409-3p GAAUGUUGCUCGGUGAACCCCU hsa-miR-221 AGCUACAUUGUCUGCUGGGUUUC mπil-iniR-409-5p AGGUUACCCGAGCAACUUUGCAU hsa-miR-221* ACCUGGCAUACAAUGUAGALTUU mπil-miR-410 AAUAUAACACAGAUGGCCUGU hsa-πuR-222 AGCUACAUCUGGCUACUGGGU mml-πuR-411 UAGUAGACCGUAUAGCGUACG hsa-πuR-222* CUCAGUAGCCAGUGUAGAUCCU mml-miR-412 ACUUCACCUGGUCCACUAGCCGU hsa-miR-223 UGUCAGUUUGUCAAAUACCCCA mml-miR-421 AUCAACAGACAUUAAUUGGGCGC hsa-miR-223* CGUGUAUUUGACAAGCUGAGUU mml-miR-422a ACUGGACUCAGGGUCAGAAGGC hsa-miR-224 CAAGUCACUAGUGOUUCCGUU raml-miR-423-3p AGCUCGGUCUGAGGCCCCUCAGU hsa-miR-23a AUCACAUUGCCAGGGAUUUCC raml-iniR-423-5p UGAGGGGCAGAGAGCGAGACUUU hsa-miK-23a* GGGGUUCCUGGGGAUGGGAUUU mml-miR-424 CAGCAGCAAUUCAUGUUUUGAA hsa-miR-23b AUCACAUUGCCAGGGAUUACC mml miR-425 AAUGACACGAUCACUCCCGUUGA hsa-raiR-23b* UGGGUUCCUGGCAUGCUGAUUU mml-miR-429 UAAUACUGUCUGGUAAAACCGU hsa-miR-24 UGGCUCAGUUCAGCAGGAACAG πunl-πuR-431 UGUCUUGCAGGCCGUCAUGCA hsa-miR-24-1* UGCCUACUGAGCUGAUAUCAGU rmτJ-miR-432 UCUUGGAGUAGGUCAUUGGGUGG hsa-miR-24-2* UGCCUACUGAGCUGAAACACAG mml-miR-433 AUCAUGAUGGGCUCCUCGGUGU hsa-miR-25 CAUUGCACUUGUCUCGGUCUGA mml-miR-448 UUGCAUAUGUAGGAUGUCCCAU hsa-πuR-25* AGGCGGAGACUUGGGCAAUUG mml-miR-449a UGGCAGUGUAUUGUUAGCUGGU hsa-πuR-26a UUCAAGUAAUCCAGGAUAGGCU mml-miR-449b AGGCAGUGUAUUGUUAGCUGGC hsa-miR-26a-l* CCUAUUCUUGGUUACUUGCACG mml-miR-450a UUUUGCGAUGUGUUCCUAAUAU hsa-miR-26a-2* CCUAUUCUUGAUUACUUGUUUC mm]-mιR-450b-3p UUGGGAUCAUUUUGCAUCCAUA hsa-miR-26b UUCAAGUAAUUCAGGAUAGGU mml-miR-4S0b-5p UUUUGCAAUAUGUUCCUGAAUA hsa-miR-26b* CCUGUUCUCCAUUACUUGGCUC mml-miR-45] AAACCGUUACCAUUACUGAGUU hsa-miR-27a UUCACAGUGGCUAAGUUCCGC mml-miR-452 AACUGUUUGCAGAGGAAACUGA hsa-miR-27a* AGGGCUUAGCUGCUUGUGAGCA mml-miR-453 AGGUUGUCCGUGGUGAGUUCGCA hsa-miR-27b UUCACAGUGGCUAAGUUCUGC mml-miR-454 UAGUGCAAUAUUGCUUAUAGGGU hsa-nuR-27b* AGAGCUUAGCUGAUUGGUGAAC mml-imR-455-3p GCAGUCCAUGGGCAUAUACAC hsa-miR-28-3p CACUAGAUUGUGAGCUCCUGGA mml-miR-455-5p UAUGUGCCUUUGGACUACAUCG hsa-miR-28-5p AAGGAGCUCACAGUCUAUUGAG inml-miR-484 UCAGGCUCAGUCCCCUCCCGAU hsa-miR-296-3p GAGGGUUGGGUGGAGGCUCUCC nunl-miR-485-3p GUCAUACACGGCUCUCCUCUCU hsa-miR-2965p AGGGCCCCCCCUCAAUCCUGU mml-miR-4S5-5p AGAGGCUGGCCGUGAUGAAUUC hsa miR 297 AUGUAUGUGUGCAUGUGCAUG mml-miR-486-3p CGGOGCAGCUCAGUACAGGAU hsa-miR-298 AGCAGAAGCAGGGAGGUUCUCCCA πunl-miR-486-5p UCCUGUACUGAGCUGCCCCGAG hsa-miR-299-3p UAUGUGGGAUGGUAAACCGCUU mml-miR-487a AAUCAUACAGGGACAUCCAGUU hsa-miR-299-5p UGGUUUACCGUCCCACAUACAU raml-miR-487b AAUCGUACAGGGUCAUCCACUU hsa-πuR-29a UAGCACCAUCUGAAAUCGGUUA mml-πuR-488 UUGAAAGGCUAUUUCUUGGUC hsa-miR-29a* ACUGAUUUCUUUUGGUGUUCAG mml-miR-489 GUGACAUCACAUAUACGGCAGC hsa-miR-29b UAGCACCAUUUGAAAUCAGUGUU mml-miR-490-3p CAACCUGGAGGACUCCAUGCUG hsa-miR-29b-l* GCUGGUUUCAUAUGGUGGUUUAGA mml-miR-490-5p CCAUGGAUCUCCAGGUGGGU hsa-miR-29b-2* CUGGUUUCACAUGGUGGCUUAG mml-miR-491-3p CUUAUGCAAGAUUCCCUUCUAC hsa-miR-29o UAGCACCAUUUGAAAUCGGUUA mml-miR-491-5p AGUGGGGAACCCUUCCAUGAGG hsa-miR-29c* UGACCGAUUUCUCCUGGUGUUC mml-miR-492 AGGACCUGCGGGACAAGAUUCUU hsa-miR-300 UAUACAAGGGCAGACUCUCUCU mtnl-miR-493 UGAAGGUCUACUGUGUGCCAGG hsa-miR-301a CAGUGCAAUAGUAUUGUCAAAGC mml-miR-494 UGAAACAUACACGGGAAACCUC hsa-miR-301b CAGUGCAAUGAUAUUGUCAAAGC mml-miR-495 AAACAAACAUGGUGCACUUCUU hsa-miR-302a UAAGUGCUUCCAUGUUUUGGUGA mml-miR-496 UGAGUAUUACAUGGCCAAUCUC hsa-πuR-302a* ACUUAAACGUGGAUGUACUUGCU mml-miR-497 CAGCAGCACACUGUGGUUUGU hsa-miR-302b UAAGUGCUUCCAUGUUUUAGUAG mml-miR-498 UUUCAAGCCAGGGGGCGUUUUUC hsa-miR-302b* ACUUUAACAUGGAAGUGCUUUC inml-raiR-499-3p AACAUCACAGCAAGUCUGUGCU hsa-miR-302o UAAGUGCUUCCAUGUUUCAGUGG mml-miR-499-5p UUAAGACUUGCAGUGAUGUUU hsa-miR-302o* UUUAACAUGGGGGUACCUGCUG mml-miR-500 UAAUCCUUGCUACCUGGGUGAGA hsa-miR-302d UAAGUGCUUCCAUGUUUGAGUGU mml-miR-501 AAUCCUUUGUCCCUGGGUGAGA hsa-miR-302d* ACUUUAACAUGGAGGCACUUGC mml-miR-502-3p AAUGCACCUGGGCAAGGAUUCA hsa-miR-302e UAAGUGCUUCCAUGCUU mml-miR-502-5p AUCCUUGCUAUCUGGGUGCUA hsa-miR-302f UAAUUGCUUCCAUGUUU mml-miR-503 UAGCAGCGGGAACAGUUCUGCAG hsa-miR-30a UGUAAACAUCCUCGACUGGAAG mml-nuR-504 AGACCCUGGUCUGCACUCUAUC hsa-miR-30a* CUUUCAGUCGGAUGUUUGCAGC mml-miR-505 CGUCAACACUUGCUGGUUUCCU hsa-πuR-30b UGUAAACAUCCUACACUCAGCU mml-tniR-506 UAAGGCACCCUUCUGAGUAGA hsa-miR-30b* CUGGGAGGUGGAUGUUUACUUC mml-miR-507 UUUUGCACCUUUUGGAGUGAA hsa-miR-30c UGUAAACAUCCUACACUCUCAGC mml-miR-508 UGAUUGUCGCCUUUUUGAGUAGA hsa-miR-30c-l * CUGGGAGAGGGUUGUUUACUCC mml-miR-509 UGAUUGGUAUGUCUGUGGGUAGA hsa-miR-30o-2* CUGGGAGAAGGCUGUUUACUCU mml-πuR-510 UACUCCGGAGAGUGGCAAUCACA hsa-miR-30d UGUAAACAUCCCCGACUGGAAG mml-miR-511 UGUCUUUUGCUCUGCAGUCA hsa-miR-30d* CUUUCAGUCAGAUGUUUGCUGC mml-miR-512-3p AAGUGCUGUCAUUGCUGAGAUC hsa-miR-30e UGUAAACAUCCUUGACUGGAAG mral-πuR-512-5p CACUCAGCCUCGGGGGCACUUUC hsa-miR-30e* CUUUCAGUCGGAUGUUUACAGC mml-miR-513a UUCACAGGGAGGUGUCAUUUAU hsa-miR-31 AGGCAAGAUGCUGGCAUAGCU mml-miR-513b UUCACAAGGAGGUGUCAUUUAU hsa-miR-31* UGCUAUGCCAACAUAUUGCCAU mml-miR-514 AUUGACACUUCUGUGAGUAGA hsa miR 32 UAUUGCACAUUACUAAGUUGCA mml miR-516a-3p UGUUUCCUUCCCGAGQGU hsa miR 32* CAAUUUAGUGUGUGUGAUAUUU mml miR-516a-5p GUCUCGAGGAAAGAAGCACUUU hsa πuR-320a AAAAGCUGGGUUGAGAGGGCGA mml-miR-5I7a AUCGUGCAUCCUUUUAGAGUGU hsa-miR-320b AAAAGCUGGGUUGAGAGGGCAA mml-miR-517b UCGUGCAUCCUUUUAGAGUGUU hsa-πuR-320c AAAAGCUGGGUUGAGAGGGU mml-miR-518a-3p GAAAGUGCUUCUCUUUGCUGG hsa-πuR-320d AAAAGCUGGGUUGAGAGGA mml-miR-518a-5p CUACAAAGGGAAGCCCUUUC hsa-πuR-323-3p CACAUUACACGGUCGACCUCU mml-miR-518b CAAAGCGCUCCCCUUUAGAGG hsa miR 323-5p AGGUGGUCCGUGGCGCGUUCGC mml-miR-518c CAAAGCGCUUCUCUUUAGAGAGU hsa-miR-32₄ 3p ACUGCCCCAGGUGCUGCUGG mml-miR-518d CAAAGCGCUUCUCUUUAGAGA hsa-miR-324-5p CGCAUCCCCUAGGGCAUUGGUGU mmi-miR-518c AAAAUGGUUCCCUUUAGAGUGU hsa-miR-325 CCUAGUAGGUGUCCAGUAAGUGU mm]-miR-S18f AAAGCGCUUCCCUUCAGAGGA hsa-miR-326 CCUCUGGGCCCUUCCUCCAG mml miR 519a AAAGUGCUUCCUUUUAG AGGGUUAC hsa-miR-328 CUGGCCCUCUCUGCCCUUCCGU mml-miR-519b AACGUGC AUCCCUUUAGAGGGUU hsa-miR-329 AACACACCUGGUUAACCUCUUU mml-miR-519c AAAGUGC AUCAUUUUAGAGGAU hsa-miR 330 3p GCAAAGCACACGGCCUGCAGAGA mml-miR-519d CAAAGUGCUUCCUUUUAGAGUG hsa-miR-330-5p UCUCUGGGCCUGUGUCUUAGGC mml miR 520a AAAGUGCUUCCCUUUGGACUGU bsa-miR-331-3p GCCCCUGGGCCUAUCCUAGAA mml miR-520b AAAGUGCUUCCUUUUAGAGGG hsa-miR-331-5p CUAGGUAUGGUCCCAGGGAUCC mml miR 520c AAAGUGCUUCCUUUUAGAGGGUU hsa-miR-335 UCAAGAGCAAUAACGAAAAAUGU mml-miR-520d-3p AAAGUGCUUCUCUUUGCUGGGU hsa-πuR-335* UUUUUCAUUAUUGCUCCUGACC mml miR 52Od 5p CUACAAAGGGAAGCCCUUUC hsa-miR-337-3p CUCCUAUAUGAUGCCUUUCUUC mml-miR-520e AAAGUGCUUCCUUUUAGAGGG hs--miR-337-5p GAACGGCUUCAUACAGGAGUU πunl-miR-520f AAGUGCUUCCUUUUAGAGGGUU hsa-miR-338 3p UCCAGCAUCAGUGAUUUUGUUG mml-imR-520g ACAAAGUGCUUCCCUUCAGAGUGU hsa miR-338-5p AACAAUAUCCUGGUGCUGAGUG mml-miR-520h ACAAAGUGCUUCCUUUUAGAGU hsa-πuR-339-3p UGAGCGCCUCGACGACAGAGCCG mml-miR-521 AACGCACUUCCCUUUGGAGUGU hsa-πuR-339-5p UCCCUGUCCUCCAGGAGCUCACG mml-miR-522 AAAAUGGUUCCCUUUAGAGUGU hsa-πuR-33a GUGCAUUGUAGUUGCAUUGCA mml-miR-523a AAUGCGCUUCCCUUUAGAGGG hsa-πuR-33a* CAAUGUUUCCACAGUGCAUCAC mml-miR-523b CUCUAGAGCGAAGCGCUUUCUG hsa-πuR-33b GUGCAUUGCUGUUGCAUUGC mml-miR-523c AACGUGCAUCCCUUUAGAGGG hsa-raiR-33b* CAGUGCCUCGGCAGUGCAGCCC mml-miR-525 CUCCAGAGGGAUGCACUUUCU hsa miR 340 UUAUAAAGCAAUGAGACUGAUU mml-miR-532-3p CCUCCCACACCCAAGGCUUGCA hsa miR-340* UCCGUCUCAGUUACUUUAUAGC mml-miR-532-5p CAUGCCUUGAGUGUAGGACCGU hsa miR-342 3p UCUCACACAGAAAUCGCACCCGU mml-nnR-539 GGAGAAAUUAUCCUUGGUGUGU hsa miR 342-5p AGGGGUGCUAUCUGUGAUUGA mml-miR-542-3p UGUGACAGAUUGAUAACUGAAA hsa miR-345 GCUGACUCCUAGUCCAGGGCUC mml miR 542 5p UCGGGGAUCAUCAUGUCACGAGA hsa miR-346 UGUCUGCCCGCAUGCCUGCCUCU mml-miR-544 AUUCUGCAUUUUUAGCAAGUUC hsa-iniR-34a UGGCAGUGUCUUAGCUGGUUGU mml-miR-545 UCAGCAAACAUUUAUUGUGUGC hsa-nuR-34a* CAAUCAGCAAGUAUACUGCCCU mml-miR-548a CAAUACUGGCAAUUACUUUUCC hsa-miR-34b CAAUCACUAACUCCACUGCCAU mml-miR-548b CAAAAACCUCAAUUGCUUUUGU hsa miR-34b* UAGGCAGUGUCAUUAGCUGAUUG mml-miR-548c CAAAACCGGCAAUUACUUCUGC hsa-miR-34o-3p AAUCACUAACCACACGGCCAGG mml-miR-548d-3p CAAAAACCACAAUUUCUUUUGC hsa-miR-34c-5p AGGCAGUGUAGUUAGCUGAUUGC mml-miR-548d-5p GGCAAAAACCACAAUUUCUUUU hsa-raiR-361-3p UCCCCCAGGUGUGAUUCUGAUUU mml miR 548e CAAAACCGGCAGUUACUUUUGC hsa-iraR-361-5p UUAUCAGAAUCUCCAGGGGUAC mml-miR-548f CAAAACCACAGUUCCUUUUGC hsa-miR-362-3p AACACACCUAUUCAAGGAUUCA mml miR-549 AGAGCUCAUCCAUAGUUGUCA hsa-miR-362-5p AAUCCUUGGAACCUAGGUGUGAGU mml miR-550 AGUGCCUGAGGGAGUAAGAGCCC hsa-miR-363 AAUUGCACGGUAUCCAUCUGUA mml-miR 551a GCGACCCACUCUUGGUUUCCA hsa miR 363* CGGGUGGAUCACGAUGCAAUUU mml miR 551b GCGACCCAUACUUGGUUUCAG hsa-πuR-365 UAAUGCCCCUAAAAAUCCUUAU mml miR 552 AACGGGUGACUGGUUAGACAA hsa-miR-367 AAUUGCACUUUAGCAAUGGUGA mml miR 553 AAAAAGGUGAGGUUUUGUUUU hsa-miR-367* ACUGUUGCUAAUAUGCAACUCU mml miR 554 GCUAGUCCUGACUCAGCCAGU hsa-miR-369-3p AAUAAUACAUGGUUGAUCUUU mml rruR-556-3p AUAUUACAAUUAGCUGAUCUUU hsa-miR-369-5p AGAUCGACCGUGUUAUAUUCGC mml-miR-556-5p GAUGAACUCAUUGUAAUAUGAG hsa-miR-370 GCCUGCUGGGGUGGAACCUGGU mml-miR-557 GUCUGCAUGGGUGAGCCUUAUCU hsa-miR 371 3p AAGUGCCGCCAUCUUUUGAGUGU mml-miR-558 UGAGCUGCUGUACCAAAAU hsa-miR-371-5p ACUCAAACUGUGGGGGCACU mml-πuR-562 AAAGUAGCUGUACCAUUUGC hsa-miR-372 AAAGUGCUGCGACAUUUGAGCGU mml-miR-563 AGGCUGACAUACAUUUCCC hsa-miR-373 GAAGUGCUUCGAUUUUGGGGUGU mml miR-567 ACUAUGUUCUUCCAGGACAGAAC hsa-miR-373* ACUCAAAAUGGGGGCGCUUUCC mml miR 568 AUGUAUAAAUGUAUACACAC hsa-miR-374a UUAUAAUACAACCUGAUAAGUG mml-miR-569 AGUUAAUGAAUCCUGGAAAGU hsa-miR-374a* CUUAUCAGAUUGUAUUGUAAUU mml-miR-570 CAAAAGUAGCAAUUACCUUUGC hsa-miR-374b AUAUAAUACAACCUGCUAAGUG mml-miR-572 GUCCGCUCGGCGGUGGCCCA hsa miR 374b* CUUAGCAGGUUGUAUUAUCAUU mml-miR-573 CUGAAGUGAUGCAUAACCGAUCAG hsa-miR-375 UUUGUUCGUUCGGCUCGCGUGA mml-miR-576 3p AAGAUGUGGAAAAAUUGGAAUC hsa-miR-376a AUCAUAGAGGAAAAUCCACGU mml-miR-576-5p AUUCUAAUUUCUCCACAUCUUU hsa-miR-376a* GUAGAUUCUCCUUCUAUGAGUA mml-miR-577 UAGAUAAAAUAUUGGUACCUG hsa-imR-376b AUCAUAGAGGAAAAUCCAUGUU mml mιR-578 CUUCUUGUGCUCUGGGAUUGU hsa-miR-376c AACAUAGAGGAAAUUCCACGU mml-miR 579 UUCAUUUGGUACAAACCGCGAUU hsa-miR 377 AUCACACAAAGGCAACUUUUGU mml-nuR-580 UUGAGUCUGAUGAAUCAUUAGG hsa miR 377* AGAGGUUGCCCUUGGUGAAUUC mml-miR-581 UCUUGUGUUCUGUAGAUCAGU hsa miR 378 ACUGGACUUGGAGUCAGAAGG mml-miR-582-3p UAACUGGUUGAACAACUGAACC hsa-miR-378* CUCCUGACUCCAGGUCCUGUGU mml-miR-582-5p UUACAGUUGUUCAACCAGUUACU hsa-miR-379 UGGUAGACUAUGGAACGUAGG mml-miR-583 CAAAGAGGAAGGUCCCAGUAC hsa-miR-379* UAUGUAACAUGGUCCACUAACU mml-miR-584 UUAUGGUUUGCCUGGGACUGAG hsa-miR-380 UAUGUAAUAUGGUCCACAUCUU mml miR-586 UAUGCAUAUUGUAUUUUUAGGUCC hsa-miR-380* UGGUUGACCAUAGAACAUGCGC mml-nuR 587 UUUCCACAGGUGAUGAGUUAC hsa-miR-381 UAUACAAGGGCAAGCUCUCUGU mml-miR-589 UGAGAACCACGUCUGCUCUGAG hsa-miR-382 GAAGUUGUUCGUGGUGGAUUCG mml-miR-S90-3p UAAUUUUAUGUAUAAGCUGGU hsa-miR-383 AGAUCAGAAGGUGAUUGUGGCU mml-miR-590-5p GAGCUUAUUCAUAAAAGUGCAG hsa-miR-384 AUUCCUAGAAAUUGUUCAUA mml-miR-592 UUGUGUCAAUAUGCGAUGAUGU hsa-miR-409-3p GAAUGUUGCUCGGUGAACCCCU mπil-miR-593 UGUCUCUGCUGGGGUUUCU hsa-miR-409-5p AGGUUACCCGAGCAACUUUGCAU mml-miR-597 UGUGUCACUUGACGACCACUGU hsa-miR-410 AAUAUAACACAGAUGGCCUGU mml-m]R-598 UACGUCAUCGUUGUCAUCGUCA hsa-miR-411 UAGUAGACCGUAUAGCGUACG mrol-miR-599 GUUGUGUCAGUUUAUCAAAC hsa-miR-411* UAUGUAACACGGUCCACUAACC mral-miR-600 AGUUACAGACAAGAGCCUUGCUC hsa-miR-412 ACUUCACCUGGUCCACUAGCCGU mml-miR-601 UGGUCUAGGAUUGUUGGAGGAG hsa-miR-421 AUCAACAGACAUUAAUUGGGCGC mml-miR-604 GGCUGCGGGAUUCAGGAC hsa-miR-422a ACUGGACUUAGGGUCAGAAGGC mml-miR-605 UAAAUCCCACGGUGCCUUCUCCU hεa-miR-423-3p AGCUCGGUCUGAGGCCCCUCAGU mral-miR-607 GUUAUAGAUCUGGAUUGGAAC hsa-miR-423-5p UGAGGGGCAGAGAGCGAGACUUU mml-miR-609 AGGGUGUUGCUCUCAUCUCU hsa-miR-424 CAGCAGCAAUUCAUGUiIUUGAA mml miR-611 GCGAGGACCCCUCGGGGUCUGAC hsa-miR-424* CAAAACGUGAGGCGCUGCUAU mml-miR-612 CUGGGGAGGGCUUCUGAGCUCCU hsa-miR-425 AAUGACACGAUCACUCCCGUUGA mml-miR-615-3p UCCGAGCCUGGGUCUCCCUCUU hsa-miR-425* AUCGGGAAUGUCGUGUCCGCCC mml-miR-615-5p GGGGGUCCCCGGUGCUCGGAUC tisa-miR-429 UAAUACUGUCUGGUAAAACCGU mml-miR-616 AAACCCUCCAAUGACU hsa-miR-431 UGUCUUGCAGGCCGUCAUGCA mml-miR-618 AAACUCUACUUGUCCUUCUGAGU hsa-miR-431* CAGGUCGUCUUGCAGGGCUUCU mml-miR-619 GAUCUGGACAUGUUUGUGCC hsa-miR-432 UCUUGGAGUAGGUCAUUGGGUGG mml-πuR-624 CACAAGAUACUGGUAUUACCU hsa-miR-432* CUGGAUGGCUCCUCCAUGUCU mml-miR-625 GGACUGUAGAACUUUCUCCCU hsa-miR-433 AUCAUGAUGGGCUCCUCGGUGU mπd-miR-626 AGCUGUCCGAAAAUGUCUU hsa-miR-448 UUGCAUAUGUAGGAUGUCCCAU mmi-miR-627 UCCUCUUUUCUUAGAGACUCAC hsa-miR-449a UGGCAGUGUAUUGUUAGCUGGU mml-miR-628-3p UCUAGUAAGAGUGGCAGUCGA hsa-miR-449b AGGCAGUGUAUUGUUAGCUGGC mml-raiR-628-5p AUGCUGACAUAUUUACUAGAGG hsa-miR-450a UUUUGCGAUGUGUUCCUAAUAU mml-miR-631 AGACCUGGCCCAGACCUCAGC hsa-miR-450b-3p UUGGGAUCAUUUUGCAUCCAUA mml-miR-632 GUGUCUGCUUCCUGUGGGA hsa-miR-450b-5p UUUUGCAAUAUGUUCCUGAAUA raml-miR-633 CUAAUAGUAUCUACCACAAUAAA hsa-miR-451 AAACCGUUACCAUUACUGAGUU mml-miR-636 UGUGCUUGCUCGUCCCGCCUGCA hsa-miR-452 AACUGUUUGCAGAGGAAACUGA mml-miR-638 AGGGAUCGCGGGCGGGCGGCGGCCU hsa-miR-452* CUCAUCUGCAAAGAAGUAAGUG mml-miR-639 AGCGC AGCGGUCGCGAGCGCUCU hsa-miR-453 AGGUUGUCCGUGGUGAGUUCGCA mml-miR-640 AUGAUCCAGGAACCUGCCUCU hsa-miR-454 UAGUGCAAUAUUGCUUAUAGGGU mml-mjR-642 GUCCCUCUCCAAAUGUGUCUUG hsa-miR-454* ACCCUAUCAAUAUUGUCUCUGC mml-miR-643 ACUUGUAUUCUAGCUCAGGUAG hsa-miR-455-3p GCAGUCCAUGGGCAUAUACAC ππnl-miR-644 AGUGUGGCUUGCUUAGAGC hsa-miR-455-5p UAUGUGCCUUUGGACUACAUCG nunl-miR-648 AAGUGUGCAGGGCACUGAU hsa-miR-483-3p UCACUCCUCUCCUCCCGUCUU mml-miR-649 AAACCUGUGUUGUUCAAGAGUC hsa-miR-483-5p AAGACGGGAGGAAAGAAGGGAG mml-miR-650a AGGAGGCAGCGCUCUCAGGAC hsa-miR-484 UCAGGCUCAGUCCCCUCCCGAU mml-miR-650b AGGAGGCAGCGCUCUCGGGAC hsa-miR-485 3p GUCAUACACGGCUCUCCUCUCU mml-miR-S50c AGGAGGCAGCGCUCUCAG hsa-miR-485-5p AGAGGCUGGCCGUGAUGAAUUC mml-miR-650d AGGAGACAGUGCUGUCGGGAC hsa-miR-486-3p CGGGGCAGCUCAGUACAGGAU mml-miR-651 UUUAGAAU AAGCUUGACUUUUG hsa-miR-486-5p UCCUGUACUGAGCUGCCCCGAG iMnl-miR-652 AAUGGCGCCACUAGGGUUGUG hsa-miR-487a AAUCAUACAGGGACAUCCAGUU mml-miR-653 GUGUUGAAACAAUCUCUACUG hsa-miR-487b AAUCGUACAGGGUCAUCCACUU mml-πuR-654-3p UAUGUCUGCUGACCAUCACCUU hsa-miR-488 UUGAAAGGCUAUUUCUUGGUC raml-iniR-654-5p UGGUGGGCCGCAGAACAUGUGC hsa-miR-488* CCCAGAUAAUGGCACUCUCAA mml-miR-656 AAUAUUAUACAGUCAACCUCU hsa-miR-489 GUGACAUCACAUAUACGGCAGC nuπl-miR-657 GGCAGGUCCUCACCCUCUCUAGG hεa-miR-490-3p CAACCUGGAGGACUCCAUGCUG mml-miR-660 UACCCAUUGCAUAUCGGAGUUG hsa-miR-490-5p CCAUGGAUCUCCAGGUGGGU mml-miR-661 UGCCUGGGUAUCUGGCCCGUGCGU hsa-miR-491 -3p CUUAUGCAAGAUUCCCUUCUAC mml-miR-662 UCCCACGUUGUGGCCCAGCAG hsa-miR-491 -5p AGUGGGGAACCCUUCC AUGAGG mml-miR-663 AGGCGGGGCGCUGCGGGACCGC hsa-miR-492 AGGACCUGCGGGACAAGAUUCUU mml-miR-664 UAUUCAUUUAUCCCCAGCCUA hsa-miR-493 UGAAGGUCUACUGUGUGCCAGG mml-miR-668 UGUCACUCGGCUCGGCCCACUAC hsa-miR-493* UUGUACAUGGUAGGCUUUCAUU mml-miR-671-3p UCCGGUUCUCAGGGCUCCACC hsa-miR-494 UGAAACAUACACGGGAAACCUC mml-miR-671 -5p AGGAAGCCCUGG AGGGGCUGG AG hsa-raiR-495 AAACAAACAUGGUGCACUUCUU mml-miR-675 UGGUGCGGAGAGGGCCCACAGUG hsa-miR-496 UGAGUAUUACAUGGCCAAUCUC mml-miR-7 UGGAAGACUAGUGAUUUUGUUGU hsa-miR-497 CAGCAGCACACUGUGGUUUGU mml-miR-758 UUUGUGACCUGGUCCACUACCC hsa-miR-497* CAAACCACACUGUGGUGUUAGA mml-miR 765 UGGAGGAGAGGGAAGGUGCUG hsa-miR-498 UUUCAAGCCAGGGGGCGUUUUUC mml-miR-767-3p UCUGCUCAUACCCCAUGGUUUCU hsa-miR-499-3p AACAUCACAGCAAGUCUGUGCU mml-miR-767-5p UGCACCAUGGUUGUCUGAGCAUG hsa-miR-499-5p UUAAGACUUGCAGUGAUGUUU mml-miR-768-3p UCACAAUGCUGACACUCAAACUGCUGAC hsa-miR-500 UAAUCCUUGCUACCUGGGUGAGA mml-πuR-768-5p GUUGGAGGAUGAAAGUACGGAGUGAU hsa-miR-500* AUGCACCUGGGCAAGGAUUCUG mml-miR-770-5p UCCAGUACCACGUGUCAGGGCCA hsa-miR-501 -3p AAUGCACCCGGGCAAGGAUUCU mml-miR-802 CAGUAACAAAGAUUCAUCCUUGU hsa-miR-501-5p AAUCCUUUGUCCCUGGGUGAGA mml-miR-874 CUGCCCUGGCCCGAGGGACCGA hsa-miR-502-3p AAUGCACCUGGGCAAGGAUUCA mml-miR-875-3p CCUGGAAAUACUGAGGUUGUG hsa-miR-502-5p AUCCUUGCUAUCUGGGUGCUA mml-miR-875-5p UAUACCUCAGUUUUAUCAGGUG hsa-miR-503 UAGCAGCGGGAACAGUUCUGCAG mml-miR-876-3p UGGUGGUUUACAAAGUAAUUCA hsa-miR-504 AGACCCUGGUCUGCACUCUAUC mml-miR-876-5p UGGAUUUCUUUGUGAAUCACCA hsa-miR-505 CGUCAACACUUGCUGGUUUCCU πunl-miR-877 GUAGAGGAGAUGGCGCAGGG hsa-miR-505* GGGAGCCAGGAAGUAUUGAUGU mml-miR-885-3p AGGCAGCGGGGUGUAGUGGAUA hsa-miR-506 UAAGGCACCCUUCUGAGUAGA mml-miR-885-5p UCCAUUACACUACCCUGCCUCU hsa-miR-507 UUUUGCACCUUUUGGAGUGAA mml-πuR-886-3p CGCGGGUGCUUACUGACCCUU hsa-miR-508-3p UGAUUGUAGCCUUUUGGAGUAGA mml-πuR-886-5p CGGGUCGGAGUUAGCUCAAGCGG hsa-miR-508-5p UACUCCAGAGGGCGUCACUCAUG mml-miR-887 GUGAACGGGCGCCAUCCCGAGG hsa-miR-S09-3-5p UACUGCAGACGUGGCAAUCAUG mml-miR-888 UACUCAAAAAGCUGUCAGUCA hsa-miR-509-3p UGAUUGGUACGUCUGUGGGUAG mml-miR-889 UU AAUAUCGGAC AACCAUUGU hsa-miR-509-5p UACUGCAGACAGUGGCAAUCA mml-miR-890 UACUUGGAAAGGCACCAGUU hsa-miR-510 UACUCAGGAGAGUGGCAAUCAC mml-miR-891 UGCAACUUACCUGAGUCAUUGA hsa-πuR-511 GUGUCUUUUGCUCUGCAGUCA mral-miR-892 CACUGUGUCCUUUCUGCGUAG hsa-miR-512-3p AAGUGCUGUCAUAGCUGAGGUC mml-πuR-9 UCUUUGGUUAUCUAGCUGUAUGA hsa-miR-512-5p CACUCAGCCUUGAGGGCACUUUC mml-miR-920 GGGGAGCUGUAGAAGCGGUA hsa-miR-513a-3p UAAAUUUCACCUUUCUGAGAAGG mml-miR-922 GCAGCAGAGAAUGAGACUACGUC hsa-miR-513a-5p UUCACAGGGAGGUGUCAU mml-miR-924 AGAGUCUUGUGUUGUCUUGC hsa-miR-513b UUCACAAGGAGGUGUCAUUUAU mml-miR-92a UAUUGCACUUGUCCCGGCCUGU hsa-miR-513o UUCUCAAGGAGGUGUCGUUUAU πunl-miR-92b UAUUGCACUCGUCCCGGCCUCC hsa-miR-514 AUUGACACUUCUGUGAGUAGA mml-miR-93 AAAGUGCUGUUCGUGCAGGUAG hsa-miR-515-3p GAGUGCCUUCUUUUGGAGCGUU mml-miR-933 UGUGCGCAGGGAGACCUCUCCC hsa-miR-515-5p UUCUCCAAAAGAAAGCACUUUCUG mml-miR-934 UGUCUACUACUGGAGACACUG hsa-miR-516a-3p UGCUUCCUUUCAGAGGGU minl-miR-936 ACAGGAGAGGGAGGAAUCGCAG hsa-raiR-516a-5p UUCUCGAGGAAAGAAGCACUUUC mml-miR-937 AUCCGCACUCUGACUCUCCACC hsa-miR-516b AUCUGGAGGUAAGAAGCACUUU mml-miR-938 UGCACUUAAAGAUGAAGCCGGU hsa-miR-516b* UGCUUCCUUUCAGAGGGU mml-miR-939 UGGGGAGCUGAGGCUCUGGGGGUG hsa-miR-517* CCUCUAGAUGGAAGCACUGUCU mml-miR-940 AAGGCAGGGCCCCCGCUCCCC hsa-miR-517a AUCGUGC AUCCCUUUAGAGUGU πunl-miR-942 CUUCUCUGUUUUGGCCAUGUG hsa-miR-517b UCGUGCAUCCCUUUAGAGUGUU mml-miR-944 AAAUUAUUGUAUAUCAGAUGAG hsa-miR-517c AUCGUGCAUCCUUUUAG AGUGU ππnl-miR-95 UUCAACGGGUAUUUAUUGAGCA hsa-miR-518a-3p GAAAGCGCUUCCCUUUGCUGGA mml-miR-96 UUUGGCACUAGCACAUUUUUGC hsa-miR-S18a-5p CUGCAAAGGGAAGCCCUUUC mml-miR-98 UGAGGUAGUAAGUUGUAUUGUU hsa-miR-518b CAAAGCGCUCCCCUUUAGAGGU raml-miR-99a AACCCGUAGAUCCGAUCUUGUG hsa-miR-518o CAAAGCGCUUCUCUUUAGAGUGU mml-miR-99b CACCCGUAGAACCGACCUUGCG hsa-miR-518c* UCUCUGGAGGGAAGCACUUUCUG mmu-let-7a UGAGGUAGUAGGUUGUAUAGUU hsa-πuR-518d-3p CAAAGCGCUUCCCUUUGGAGC mmu-lel-7a* CUAUACAAUCUACUGUCUUUCC hsa-miR-518d-5p CUCUAGAGGGAAGCACUUUCUG mmu-let-7b UGAGGUAGUAGGUUGUGUGGUU hsa miR 518β AAAGCGCUUCCCUUCAGAGUG mmu-let-7b* CUAUACAACCUACUGCCUUCCC hsa-miR-518e* CUCUAGAGGGAAGCGCUUUCUG mmu-let-7o UGAGGUAGUAGGUUGUAUGGUU hsa-miR-S18f GAAAGCGCUUCUCUUUAGAGG ramu-let-7c-l* CUGUACAACCUUCUAGCUUUCC hsa-miR-518f* CUCUAGAGGGAAGC ACUUUCUC mmu-let-7c-2* CUAUACAAUCUACUGUCUUUCC hsa-miR-519a AAAGUGCAUCCUUUUAGAGUGU mmu-let-7d AGAGGUAGUAGGUUGCAUAGUU hsa-miR-519a* CUCUAGAGGGAAGCGCUUUCUG mmu-let-7d* CUAUACGACCUGCUGCCUUUCU hsa-miR-519b-3p AAAGUGCAUCCUUUUAGAGGUU mmu-let-7e UGAGGUAGGAGGUUGUAUAGUU hsa-miR-519b-5p CUCUAGAGGGAAGCGCUUUCUG mmu-let-7f UGAGGUAGUAGAUUGUAUAGUU hsa-miR-519o-3p AAAGUGC AUCUUUUUAGAGGAU mmu-let-7f* CUAUACAAUCUAUUGCCUUCCC hsa-miR-519c-5p CUCUAGAGGGAAGCGCUUUCUG mmu-let-7g UGAGGUAGUAGUUUGUACAGUU hsa-miR-519d CAAAGUGCCUCCCUUUAGAGUG mmu-lεt-7g* ACUGUACAGGCCACUGCCUUGC hsa-miR-519e AAGUGCCUCCUUUUAGAGUGUU mmu-let-7i UGAGGUAGUAGUUUGUGCUGUU hsa-miR-519e* UUCUCCAAAAGGGAGCACUUUC mmu-let-7i* CUGCGCAAGCUACUGCCUUGCU hsa-miR-520a-3p AAAGUGCUUCCCUUUGGACUGU mmu-miR-1 UGGAAUGUAAAGAAGUAUGUAU hsa-miR-520a-5p CUCCAGAGGGAAGUACUUUCU mmu-miR-100 AACCCGUAGAUCCGAACUUGUG hsa-miR-520b AAAGUGCUUCCUUUUAGAGGG mmu-miR-lOla UACAGUACUGUGAUAACUGAA hsa-miR-520o-3p AAAGUGCUUCCUUUUAGAGGGU mmu-miR-101a* UCAGUUAUCACAGUGCUGAUGC hsa-miR-520c-5p CUCUAGAGGGAAGCACUUUCUG mmu-miR-lOlb UACAGUACUGUGAUAGCUGAA hsa-miR-520d-3p AAAGUGCUUCUCUUUGGUGGGU mmu-miR-103 AGCAGCAUUGUACAGGGCUAUGA hsa-miR-520d-5p CUACAAAGGGAAGCCCUUUC mmu-miR-105 CCAAGUGCUCAGAUGCUUGUGGU hsa-miR-520e AAAGUGCUUCCUUUUUGAGGG mmu miR 106a CAAAGUGCUAACAGUGCAGGUAG hsa-miR-520f AAGUGCUUCCUUUUAGAGGGUU mmu-miR-106b UAAAGUGCUGACAGUGCAGAU hsa-miR-520g ACAAAGUGCUUCCCUUUAGAGUGU mrou-miR-106b* CCGCACUGUGGGUACUUGCUGC hsa-miR-520h ACAAAGUGCUUCCCUUUAGAGU mmu-miR- 107 AGCAGC AUUGUAC AGGGCU AUCA hsa-miR-521 AACGCACUUCCCUUUAGAGUGU mmu-miR-1 Oa UACCCUGUAGAUCCGAAUUUGUG hsa-miR-522 AAAAUGGUUCCCUUUAGAGUGU mmu-miR-lOa* CAAAUUCGUAUCUAGGGGAAUA hsa-miR-522* CUCUAGAGGGAAGCGCUUUCUG mmu-miR-lOb UACCCUGUAGAACCGAAUUUGUG hsa-miR-523 GAACGCGCUUCCCUAUAGAGGGU mmu-miR-1 Ob* CAGAUUCGAUUCU AGGGGAAUA hsa-miR-523* CUCUAGAGGGAAGCGCUUUCUG mmu-miR-1186 GAGUGCUGGAAUUAAAGGCAUG hsa-miR-524-3p GAAGGCGCUUCCCUUUGGAGU mmu-miR-1187 UAUGUGUGUGUGUAUGUGUGUAA hsa-miR-524-5p CUACAAAGGGAAGCACUUUCUC mmu-miR-1188 UGGUGUGAGGUUGGGCCAGGA hsa-miR-525-3p GAAGGCGCUUCCCUUUAGAGCG mmu-miR-1190 UCAGCUGAGGUUCCCCUCUGUC hsa-miR-525-5p CUCCAGAGGGAUGCACUUUCU mmu-miR-1191 CAGUCUUACUAUGUAGCCCUA hsa-miR-526a CUCUAGAGGGAAGCACUUUCUG mmu-miR-1 192 AAACAAACAAACAGACCAAAUU hsa-miR-526b CUCUUGAGGGAAGCACUUUCUGU mmu-miR-1 193 UAGGUC ACCCGUUUUACUAUC hsa-miR-526b* GAAAGUGCUUCCUUUUAGAGGC mmπ-miR-1 194 GAAUGAGUAACUGCUAGAUCCU hsa-miR-527 CUGCAAAGGGAAGCCCUUUC mmu-miR-1195 UGAGUUCGAGGCCAGCCUGCUCA hsa-miR-532-3p CCUCCCACACCCAAGGCUUGCA mmu-miR-1196 AAAUCUACCUGCCUCUGCCU hsa-miR-532-5p CAUGCCUUGAGUGUAGGACCGU mmu-miR-1197 UAGGACACAUGGUCUACUUCU hsa-miR-539 GGAGAAAUUAUCCUUGGUGUGU mmu-miR-1198 UAUGUGUUCCUGGCUGGCUUGG hsa-miR-541 UGGUGGGCACAGAAUCUGGACU mmu-miR-1199 UCUGAGUCCCGGUCGCGCGG hsa-miR-541 * AAAGGAUUCUGCUGUCGGUCCCACU mmu-miR-122 UGGAGUGUGACAAUGGUGUUUG hsa-miR-542-3p UGUGACAGAUUGAUAACUGAAA mmu-πiiR-1224 GUGAGGACUGGGGAGGUGGAG hsa-miR-542-5p UCGGGGAUCAUCAUGUCACGAGA mmu-miR-124 UAAGGCACGCGGUGAAUGCC hsa-miR-543 AAACAUUCGCGGUGCACUUCUU mmu-miR-124* CGUGUUCACAGCGGACCUUGAU hsa-miR-544 AUUCUGCAUUUUUAGCAAGUUC mmu-miR-125a-3p ACAGGUGAGGUUCUUGGGAGCC hsa-miR-545 UCAGCAAACAUUUAUUGUGUGC mmu-miR-125a-5p UCCCUGAGACCCUUUAACCUGUGA hsa-miR 545* UCAGUAAAUGUUUAUUAGAUGA mmu-miR- 12Sb* ACAAGUCAGGUUCUUGGGACCU hsa-miR-548a 3p CAAAACUGGCAAUUACUUUUGC mmu-miR-12Sb-3p ACGGGUUAGGCUCUUGGGAGCU hsa-miR 548a Sp AAAAGUAAUUGCGAGUUUUACC mmu-miR- 125b-5p UCCCUGAGACCCUAACUUGUGA hsa-imR-548b-3p CAAGAACCUCAGUUGCUUUUGU mmu-raiR- 126-3p UCGUACCGUGAGUAAUAAUGCG hsa-miR-548b-5p AAAAGUAAUUGUGGUUUUGGCC mmu-miR-I26-5p CAUUAUUACUUUUGGUACGCG hsa-miR-548c-3p CAAAAAUCUCAAUUACUUOUGC mmu-miR-127 UCGGAUCCGUCUGAGCUUGGCU hsa-miR-548c-5p AAAAGUAAUUGCGGUUUUUGCC mmu-miR-127* CUGAAGCUCAGAGGGCUCUGAU hsa-miR-548d 3p CAAAAACCACAGUUUCUUUUGC mmu-miR-128 UCACAGUGAACCGGUCUCUUU hsa miR-548d-5p AAAAGUAAUUGUGGUUUUUGCC mmu-miR-129-3p AAGCCCUUACCCCAAAAAGCAU hsa-πuR-548e AAAAACUGAGACUACUUUUGCA mmu-miR-129-5p CUOtTUUGCGGUCUGGGCUUGC hsa-miR-548f AAAAACUGUAAUUACUUUU mmu-miR-l-2-as UACAUACUUCUUUACAUUCCA hsa-miR-548g AAAACUGUAAUUACUUUUGUAC mπm-miR-130a CAGUGCAAUGUUAAAAGGGCAU hsa-miR-5481i AAAAGUAAUCGCGGUUUUUGUC mmu-miR-130b CAGUGCAAUGAUGAAAGGGCAU hsa-miR-548i AAAAGUAAUUGCGGAUUUUGCC mmu-miR-130b* ACUCUUUCCCUGiπJGCACUACU hsa-miR-548j AAAAGUAAUUGCGGUCUUUGGU mmu-miR-132 UAACAGUCUACAGCCAUGGUCG hsa-miR-548k AAAAGUACUUGCGGAUUUUGCU mmu-miR-133a UUUGGUCCCCUUCAACCAGCUG hsa-miR-5481 AAAAGUAUUUGCGGGUUUUGUC mmu-miR-133a* GCUGGUAAAAUGGAACCAAAU hsa-miR-548m CAAAGGUAUUUGUGGUUUUUG mmu-miR-133b UXJUGGUCCCCUUCAACCAGCUA hsa-miR-548n CAAAAGUAAUUGUGGAUUUUGU nimu-miR 134 UGUGACUGGUUGACCAGAGGGG hsa-miR-548o CCAAAACUGCAGUUACUUUUGC mmu-πuR-13Sa UAUGGCUUUUUAUUCCU AUGUGA hsa-miR-548p UAGCAAAAACUGCAGUUACUUU mmu miR 135a* UAUAGGGAUUGGAGCCGUGGCG hsa-miR-549 UGACAACUAUGGAUGAGCUCU mmu-miR-13Sb UAUGGCUUUUCAUUCCUAUGUGA hsa-raiR-550 AGUGCCUGAGGGAGUAAGAGCCC mmu-miR-136 ACUCCAUUUGUUUUGAUGAUGG hsa-miR-550* UGUCUUACUCCCUCAGGCACAU mmu-miR-136* AUCAUCGUCUCAAAUGAGUCUU hsa-miR-551a GCGACCCACUCUUGGUUUCCA mmu-nuR-137 UUAUUGCUUAAGAAUACGCGUAG hsa-miR-551b GCGACCCAUACUUGGUUUCAG mmu-miR-138 AGCUGGUGUUGUGAAUCAGGCCG hsa-miR-551b* GAAAUCAAGCGUGGGUGAGACC mmu-nuR-138* CGGCUACUUCACAACACCAGGG hsa-miR-552 AACAGGUGACUGGUUAGACAA mmu-miR-139 3p UGGAGACGCGGCCCUGUUGGAG hsa-miR-553 AAAACGGUGAGAUUUUGUUUU mmu nuR 139-5p UCUACAGUGCACGUGUCUCCAG hsa-miR-554 GCUAGUCCUGACUCAGCCAGU mmu-miR-140 CAGUGGUUUUACCCUAUGGUAG hsa-πuR-555 AGGGUAAGCUGAACCUCUGAU mmu-miR-140* UACCACAGGGUAGAACCACGG hsa miR 556-3p AUAUUACCAUUAGCUCAUCUUU mmu-miR-141 UAACACUGUCUGGUAAAGAUGG hsa-miR-556-5p GAUGAGCUCAUUGUAAUAUGAG mmu-miR-141* CAUCUUCCAGUGCAGUGUUGGA hsa-miR-557 GUUUGCACGGGUGGGCCUUGUCU imnu-miR-142-3p UGUAGUGUiπJCCUACUUUAUGGA hsa-miR-558 UGAGCUGCUGUACCAAAAU mmu-miR-142-5p CAUAAAGUAGAAAGCACUACU hsa miR-559 UAAAGUAAAUAUGCACCAAAA mmu-miR-143 UGAGAUGAAGCACUGUAGCUC hsa miR-561 CAAAGUUUAAGAUCCUUGAAGU mmu-miR-144 UACAGUAUAGAUGAUGUACU hsa miR-562 AAAGUAGCUGUACCAUUUGC mmu-miR-145 GUCCAGUUUUCCCAGGAAUCCCU hsa miR-563 AGGUUGACAUACGUUUCCC mmu-miR-145* AUUCCUGGAAAUACUGUUCUUG hεa miR-564 AGGCACGGUGUCAGCAGGC mmu-miR-146a UGAGAACUGAAUUCCAUGGGUU hsa-miR-566 GGGCGCCUGUGAUCCCAAC mmu-miR-14βb UGAGAACUGAAUUCCAUAGGCU hsa-miR-567 AGUAUGUUCUUCCAGGACAGAAC nunu-imR-146b* GCCCUAGGGACUCAGUUCUGGU hsa-miR-568 AUGUAUAAAUGUAUACACAC mmu-rmR-147 GUGUGCGGAAAUGCUUCUGCUA hsa-πuR-569 AGUUAAUGAAUCCUGGAAAGU mmu-miR 148a UCAGUGCACUACAGAACUUUGU hsa-miR-570 CGAAAACAGCAAUUACCUUUGC mmu-miR-148a* AAAGUUCUGAGACACUCCGACU hsa-miR-571 UGAGUUGGCCAUCUGAGUGAG nunu-miR-148b UCAGUGCAUCACAGAACUUUGU hsa-miR-572 GUCCGCUCGGCGGUGGCCCA mmu-miR-149 UCUGGCUCCGUGUCUUCACUCCC hsa-miR 573 CUGAAGUGAUGUGUAACUGAUCAG mmu-miR-150 UCUCCCAACCCUUGUACCAGUG hsa-miR-574-3p CACGCUCAUGCACACACCCACA mmu-miR-150* CUGGUACAGGCCUGGGGGAUAG hsa-miR-574-5p UGAGUGUGUGUGUGUGAGUGUGU mmu-miR-151 -3p CUAGACUGAGGCUCCUUGAGG hsa-miR-575 GAGCCAGUUGGACAGGAGC mmu-miR-151-5p UCGAGGAGCUCACAGUCUAGU hsa-miR-576-3p AAGAUGUGGAAAAAUUGGAAUC mmu miR 152 UCAGUGCAUGACAGAACUUGG hsa-miR-576-5p AUUCUAAUUUCUCCACGUCUUU mmu miR-153 IΛJGCAUAGUCACAAAAGUGAUC b.sa-miR-577 UAGAUAAAAUAUUGGUACCUG mmu miR-154 UAGGUUAUCCGUGUUGCCUUCG hsa-miR-57S CUUCUUGUGCUCUAGGAUUGU mmu miR-154* AAUCAUACACGGUUGACCUAUU h.sa-miR-579 UUCAUUUGGUAUAAACCGCGAUU mmu miR-155 UUAAUGCUAAUUGUGAUAGGGGU b.sa-miR-580 UUGAGAAUGAUGAAUCAUUAGG mmu-miR-15a UAGCAGCACAUAAUGGUUUGUG hsa-miR-581 UCUUGUGUUCUCUAGAUCAGU mmu-miR-15a* CAGGCCAUACUGUGCUGCCUCA hsa-miR-582-3p UAACUGGUUGAACAACUGAACC mmu-miR-15b UAGCAGC ACAUCAUGGUUUAC A hsa-πuR-582-5p ITUACAGUUGUUCAACCAGUUACU mmu mιR-15b* CGAAUCAUUAUUUGCUGCUCUA hsa-miR-583 CAAAGAGGAAGGUCCCAUUAC mmu-miR-16 UAGCAGCACGUAAAUAUUGGCG hsa-miR-584 UUAUGGUUUGCCUGGGACUGAG mmu-miR-16* CCAGUAUUGACUGUGCUGCUGA hsa-miR-585 UGGGCGUAUCUGUAUGCUA mmu-miR-17 CAAAGUGCUUACAGUGCAGGUAG hsa miR 586 UAUGCAUUGUAUUUUUAGGUCC mmu-miR-17* ACUGCAGUGAGGGCACUUGUAG hsa-miR-587 UUUCCAUAGGUGAUGAGUCAC mmu-miR-181a AACAXJUCAACGCUGUCGGUGAGU hsa-miR-588 UUGGCCACAAUGGGUUAGAAC mmu-miR-181a-l* ACCAUCGACCGUUGAUUGUACC hsa-miR-589 UGAGAACCACGUCUGCUCUGAG mmu-miR- 181 a-2* ACCG ACCGUUGACUGU ACCUUG hsa-miR-589* UCAGAACAAAUGCCGGUUCCCAGA mmu-miR-181b AACAUUCAUUGCUGUCGGUGGGU hsa-miR-590-3p UAAUUUUAUGUAUAAGCUAGU mmu-miR-1810 AACAUUCAACCUGUCGGUGAGU hsa-miR-590-5p GAGCUUAUUCAUAAAAGUGCAG mmu-miR-181d AACAUUCAUUGUUGUCGGUGGGU hsa-miR 591 AGACCAUGGGUUCUCAUUGU mmu-miR-182 UUUGGCAAUGGUAGAACUCACACCG hsa miR 592 UUGUGUCAAUAUGCGAUGAUGU mmu-miR-183 UAUGGCACUGGUAGAAUUCACU hsa miR-593 UGUCUCUGCUGGGGUUUCU mmu-miR-183* GUGAAUUACCGAAGGGCCAUAA hsa-miR 593* AGGCACCAGCCAGGCAUUGCUCAGC mmu-miR-184 UGGACGGAGAACUGAUAAGGGU hsa-miR-595 GAAGUGUGCCGUGGUGUGUCU mmu-miR-185 UGGAGAGAAAGGCAGUUCCUGA hsa-miR-596 AAGCCUGCCCGGCUCCUCGGG mmu-miR-186 CAAAGAAUUCUCCUUUUGGGCU hsa-miR-597 UGUGUCACUCGAUGACCACUGU mmu-miR-186* GCCCUAAGGUGAAUUUUUUGGG hsa-miR-598 UACQUCAUCQUUQUCAUCGUCA mmu πuR-187 UCGUGUCUUGUGUUGCAGCCGG hsa-miR-599 GUUGUGUCAGUUUAUCAAAC mmu imR-188-3p CUCCCACAUGCAGGGUUUGCA hsa-miR-600 ACUUACAGACAAGAGCCUUGCUC mmu-miR-1 S8-5p CAUCCCUUGCAUGGUGGAGGG hsa-miR-601 UGGUCUAGGAUUGUUGGAGGAG mmu-miR-18a UAAGGUGCAUCUAGUGCAGAUAG hsa-miR-602 GACACGGGCGACAGCUGCGGCCC mmu-miR-18a* ACUGCCCUAAGUGCUCCUUCUG hεa-miR-603 CACACACUGCAAUUACUUUUGC mmu-miR-18b UAAGGUGCAUCUAGUGCUGUUAG hsa-miR-604 AGGCUGCGGAAUUCAGGAC mmu-miR-190 UGAUAUGUUUGAUAUAUUAGGU hsa-miR-605 UAAAUCCCAUGGUGCCUUCUCCU mmu-miR-190b UGAUAUGUUUGAUAUUGGGUU hsa-miR-606 AAACUACUGAAAAUCAAAGAU mmu-miR-191 CAACGGAAUCCCAAAAGCAQCUG hsa-miR-607 GUUCAAAUCCAGAUCUAUAAC mmu-miR-191* GCUGCACUUGGAUUUCGUUCCC hsa-miR-608 AGGGGUGGUGUUGGGACAGCUCCGU mmu-miR-192 CUGACCUAUGAAUUGACAGCC hsa-miR-609 AGGGUGUUUCUCUCAUCUCU mmu-miR-193 AACUGGCCUACAAAGUCCCAGU hsa-miR-610 UGAGCUAAAUGUGUGCUGGGA mmu-miR-193* UGGGUCUUUGCGGGCAAGAUGA hsa-miR-611 GCGAGGACCCCUCGGGGUCUGAC mmu-miR-193b AACUGGCCCACAAAGUCCCGCU hsa-miR-612 GCUGGGCAGGGCUUCUGAGCUCCUU mmu-miR-194 UGUAACAGCAACUCCAUGUGGA hsa-miR-613 AGGAAUGUUCCUUCUUUGCC mmu-miR-195 UAGCAGCACAGAAAUAUUGGC hsa-miR-614 GAACGCCUGUUCUUGCCAGGUGG mmu-miR-196a UAGGUAGUUUCAUGUUGUUGGG hsa-miR-615-3p UCCGAGCCUGGGUCUCCCUCUU mmu-miR-196a* UCGGCAACAAGAAACUGCCUGA hsa-miR-615-5p GGGGGUCCCCGGUGCUCGGAUC mmu-miR-196b UAGGUAGUUUCCUGUUGUUGGG hsa-miR 616 AGUCAUUGGAGGGUUUGAGCAG mmu-mjR-197 UUCACCACCUUCUCCACCCAGC hsa-miR-616* ACUCAAAACCCUUCAGUGACUU mmu-miR-199a-3p ACAGUAGUCUGCACAUUGGUUA hsa-miR-617 AGACUUCCCAUUUGAAGGUGGC mmu-miR- 199a-5p CCCAGUGUUCAGACUACCUGUUC hsa-miR-618 AAACUCUACUUGUCCUUCUGAGU mmu-miR-199b ACAGUAGUCUGCACAUUGGUUA hsa-miR-619 GACCUGGACAUGUUUGUGCCCAGU mmu-πuR-199b* CCCAGUGUUUAGACUACCUGUUC hsa-miR-620 AUGGAGAUAGAUAUAGAAAU mmu-miR-19a UGUGCAAAUCUAUGCAAAACUGA hsa-miR-621 GGCUAGCAACAGCGCUUACCU mmu-miR-19a* UAGUUUUGCAUAGUUGCACUAC hsa-miR-622 ACAGUCUGCUGAGGUUGGAGC mmu-miR-19b UGUGCAAAUCCAUGCAAAACUGA hsa-miR-623 AUCCCUUGCAGGGGCUGUUGGQU mmu-miR-200a UAACACUGUCUGGUAACGAUGU hsa-miR-624 CACAAGGUAUUGGUAUUACCU mmu-miR-200a* CAUCUUACCGGACAGUGCUGGA hsa-miR-624* UAGUACCAGUACCUUGUGUUCA mπra-miR-200b UAAUACUGCCUGGUAAUGAUGA hsa-miR-625 AGGGGGAAAGUUCUAUAGUCC mmu nuR 200b* CAUCUUACUGGGCAGCAUUGGA hsa-miR-625* GACUAUAGAACUUUCCCCCUCA mmu-miR-200o UAAUACUGCCGGGUAAUGAUGGA hsa-miR-626 AGCUGUCUGAAAAUGUCUU mmu-miR-200c* CGUCUUACCCAGCAGUGUUUGG hsa-miR-627 GUGAGUCUCUAAGAAAAGAGGA mmu-miR-201 UACUCAGUAAGGCAUUGUUCUU hsa-miR-628-3p UCUAGUAAGAGUGGCAGUCGA mmu-miR-202-3p AGAGGUAUAGCGCAUGGGAAGA hsa-miR-628-5p AUGCUGACAUAUUUACUAGAGG mmu-miR-202-5p UUCCUAUGCAUAUACUUCUUU hsa-miR-629 UGGGUUUACGUUGGGAGAACU mmu-miR-203 GUGAAAUGUUUAGGACCACUAG hsa-miR-629* GUUCUCCCAACGUAAGCCCAGC mmu-miR-203* AGUGGUUCUUGACAGUUCAACA hsa-miR-630 AGUAUUCUGUACCAGGGAAGGU mmu-miR-204 UUCCCUUUGUCAUCCUAUGCCU hsa-miR-631 AGACCUGGCCCAGACCUCAGC mmu-miR-205 UCCUUCAUUCCACCGGAGUCUG hsa-miR-632 GUGUCUGCUUCCUGUGGGA mmu-miR-206 UGQAAUGUAAGGAAGUGUQUGG hsa-miR-633 CUAAUAGUAUCUACCACAAUAAA mmu-miR-207 GCUUCUCCUGGCUCUCCUCCCUC hsa-miR-634 AACCAGCACCCCAACUUUGGAC mmu-miR-208a AUAAGACGAGCAAAAAGCUUGU hsa-miR-635 ACUUGGGCACUGAAACAAUGUCC mmu-miR-208b AUAAGACGAACAAAAGGUUUGU hsa-πuR-636 UGUGCUUGCUCGUCCCGCCCGCA mmu-miR-20a UAAAGUGCUUAUAGUGCAGGUAG hsa-miR-637 ACUGGGGGCUUUCGGGCUCUGCGU mmu-miR-20a* ACUGCAUUACGAGCACUUAAAG hsa-miR-638 AGGGAUCGCGGGCGGGUGGCGGCCU mmu-miR-20b CAAAGUGCUCAUAGUGCAGGUAG hsa-miR-639 AUCGCUGCGGUUGCGAGCGCUGU mmu-πuR-20b* ACUGCAGUGUGAGCACUUCUAG hsa-miR-640 AUGAUCCAGGAACCUGCCUCU mmu-miR-21 UAGCUUAUCAGACUGAUGUUGA hsa-miR-641 AAAGACAUAGGAUAGAGUCACCUC mmu-miR-21* CAACAGCAGUCGAUGGGCUGUC hsa-miR-642 GUCCCUCUCCAAAUGUGUCUUG mmu-miR-210 CUGUGCGUGUGACAGCGGCUGA hsa-miR-643 ACUUGUAUGCUAGCUCAGGUAG mmu-miR-211 UUCCCUUUGUCAUCCUUUGCCU hsa-miR-644 AGUGUGGCUUUCUUAGAGC mmu-miR-212 UAACAGUCUCCAGUCACGGCCA hsa-miR-645 UCUAGGCUGGUACUGCUQA mmu-miR-214 ACAGCAGGCACAGACAGGCAGU hsa-miR-646 AAGCAGCUGCCUCUGAGGC mmu-miR-214* UGCCUGUCUACACUUGCUGUGC hsa-miR-647 GUGGCUGCACUCACUUCCUUC mmu-miR-215 AUGACCUAUGAUUUGACAGAC hsa-miR-648 AAGUGUGCAGGGCACUGGU mmu-miR-216a UAAUCUCAGCUGGCAACUGUGA hsa-miR-649 AAACCUGUGUUGUUCAAGAGUC mmu-miR-216b AAAUCUCUGCAGGCAAAUGUGA hsa-miR-650 AGGAGGCAGCGCUCUCAGGAC mmu-miR-217 UACUGCAUCAGGAACUGACUGGA hsa-miR-651 UUUAGGAUAAGCUUGACUUUUG mmu-miR-218 UUGUGCUUGAUCUAACCAUGU hsa-miR-652 AAUGGCGCCACUAGGGUUGUG ramu-miR-218-1* AAACAUGGUUCCGUCAAGCACC hsa-mιR-653 GUGUUGAAACAAUCUCUACUG mmu-miR-218-2* CAUGGUUCUGUCAAGCACCGCG hsa-miR-654-3p UAUGUCUGCUGACCAUCACCUU mmu-miR-219 UGAUUGUCCAAACGCAAUUCU hsa-miR-654-5p UGGUGGGCCGCAGAACAUGUGC mmu-miR-22 AAGCUGCCAGUUGAAGAACUGU hsa-miR-655 AUAAUACAUGGUUAACCUCUUU mmu-miR-22* AGUUCUUCAGUGGCAAGCUUUA hsa-miR-656 AAUAUUAUACAGUCAACCUCU mmu-miR-220 CCACCACAGUGUCAGACACUU hsa-πuR-657 GGCAGGUUCUCACCCUCUCUAGG mmu-miR-221 AGCUACAUUGUCUGCUGGGUUUC hsa-miR-658 GGCGGAGGGAAGUAGGUCCGUUGGU mmu-miR-222 AGCUACAUCUGGCUACUGGGU hsa-miR-659 CUUGGUUCAGGGAGOGUCCCCA mmu-miR-223 UGUCAGUUUGUCAAAUACCCCA hsa-miR-660 UACCCAUUGCAUAUCOGAGUUG mmu-tniR-224 UAAGUCACUAGUGGUUCCGUU hsa-miR-661 UGCCUQGGUCUCUGGCCUGCGCGU mmu-miR-23a AUCACAUUGCCAGGGAUUUCC hsa-miR-662 UCCCACGUUGUGGCCCAGCAG mmu-miR-23b AUCACAUUGCCAGGGAUUACC hsa-miR-663 AGGCGGGGCGCCGCGGGACCGC mmu-miR-24 UGGCUCAGUUCAGCAGGAACAG hsa-miR-663b GGUGGCCCGGCCGUGCCUGAGG mmu-miR-24-1* GUGCCUACUGAGCUGAUAUCAGU hsa-miR-664 UAUUCAUUUAUCCCCAGCCUACA mmu-miR-24-2* GUGCCUACUGAGCUGAAACAGU hsa-miR-664* ACUGGCUAGGGAAAAUGAUUGGAU mmu-miR-25 CAUUGCACUUGUCUCGGUCUGA hsa-miR-665 ACCAGGAGGCUGAGGCCCCU mmu-miR-26a UUCAAGUAAUCCAGGAUAGGCU hsa miR-668 UGUCACUCGGCUCGGCCCACUAC minu-miR-26b UUCAAGUAAUUCAGGAUAGGU hsa miR 671-3p UCCGGUUCUCAGGGCUCCACC mmu-miR-26b* CCUGUUCUCCAUUACUUGGCUC hsa miR-671-5p AGGAAGCCCUGGAGGGGCUGGAG mmu miR 27a UUCACAGUGGCUAAGUUCCGC hsa miR-675 UGGUGCGGAGAGGGCCCACAGUG mmu-miR-27a* AGGGCUUAGCUGCUUGUGAGCA hsa-πuR-7 UGGAAGACUAGUGAUUUUGtJUGU mπm-miR-27b UUCACAGUGGCUAAGUUCUGC hsa-miR-708 AAGGAGCUUACAAUCUAGCUGGG mmu-miR 27b* AGAGCUUAGCUGAUUGGUGAAC hsa-miR 708* CAACUAGACUGUGAGCUUCUAG mmu-πuR-28 AAGGAGCUCACAGUCUAUUGAG hsa miR-7-1* CAACAAAUCACAGUCUGCCAUA mmu-miR-28* CACUAGAUUGUGAGCUGCUGGA hsa-miR-7-2* CAACAAAUCCCAGUCUACCUAA mmu-miR-290-3p AAAGUGCCGCCUAGUUUUAAGCCC hsa-miR-720 UCUCGCUGGGGCCUCCA. mmu-miR-290-5p ACUCAAACUAUGGGGGCACUUU hsa-miR-744 UGCGGGGCUAGGGCUAACAGCA mmu-miR-291a-3p AAAGUGCUUCCACUUUGUGUDC hsa-miR 744* CUGUUGCCACUAACCUCAACCU mmu miR 29Ia-Sp CAUCAAAGUGGAGGCCCUCUCU hsa-miR-758 UUUGUGACCUGGUCCACUAACC mmu-miR-291b-3p AAAGUGCAUCCAUUUUGUUUGU hsa-miR-760 CGGCUCUGGGUCUGUGGGGA mmu miR-291b-5p GAUCAAAGUGGAGGCCCUCUCC hsa-miR-765 UGGAGGAGAAGGAAGGUGAUG mmu-miR-292-3p AAAGUGCCGCCAGGUUUUGAGUGU hsa-miR-766 ACUCCAGCCCCACAGCCUCAGC mmu-miR-292 5p ACUCAAACUGGGGGCUCUUUUG hsa πuR 767-3p UCUGCUCAUACCCCAUGGUUUCU mmu-miR-293 AGUGCCGCAGAGUUUGUAGUGU hsa-πuR-767-5p UGCACCAUGGUUGUCUGAGCAUG mmu-miR-293 * ACUCAAACUGUGUGACAUUUUG hsa-mιR-768-3p UCACAAUGCUGACACUCAAACUGCUGAC mmu-miR 294 AAAGUGCUUCCCUUUUGUGUGU hsa-πnR-768-5p GUUGGAGGAUGAAAGUACQOAOUGAU mmu miR 294* ACUCAAAAUGGAGGCCCUAUCU hsa-πuR-769 3p CUGGGAUCUCCGGGGUCUUGGUU mmu πuR 29S AAAGUGCUACUACUUUUGAGUCU hsa-miR-769 Sp UGAGACCUCUGGGUUCUGAGCU mmu miR-295* ACUCAAAUGUGGGGCACACUUC hsa miR-770-5p UCCAGUACCACGUGUCAGGGCCA mmu miR-296-3p GAGGGUUGGGUGGAGGCUCUCC hsa-πuR-802 CAGUAACAAAGAUUCAUCCUUGU mmu-miR-296-5p AGGGCCCCCCCUCAAUCCUGTJ hsa imR-873 GCAGGAACUUGUGAGUCUCCU mmu miR-297a AUGUAUGUGUGCAUGUGCAUGU hsa miR 874 CUGCCCUGGCCCGAGGGACCGA mmu-miR-297a* UAUACAUACACACAUACCCAUA hsa-miR-875 3p CCUGGAAACACUGAGGUUGUG mmu-miR-297b-3p UAUACAUACACACAUACCCAUA hsa-miR-875 5p UAUACCUCAGUUUUAUCAGGUG mmu-miR-297b 5p AUGUAUGUGUGCAUGAACAUGU hsa-miR 876-3p UGGUGGUUUACAAAGUAAUUCA mmu miR 297c AUGUAUGUGUCCAUGUACAUGU hsa miR 876 5p UGGAUUUCUUUGUGAAUCACCA mmu miR-297c* UAUACAUACACACAUACCCAUA hsa miR 877 GUAGAGGAGAUQGCGCAGGG mmu-miR-298 CGCAGAGGAGGGCUGUUCUUCCC hsa miR-877* UCCUCUUCUCCCUCCUCCCAG mmu-miR-299 UAUGUGGGACGGUAAACCGCUU hsa nuR-8S5-3p AGGCAGCGGGGUGU AGUGGAUA mmu-miR-299* UGGUUUACCGUCCCACAUACAU hsa-miR-885-5p UCCAUUACACUACCCUGCCUCU mmu-miR 29a UAGCACCAUCUGAAAUCGGUUA hsa-miR 886 3p CGCGGGUGCUUACUGACCCUU mmu-miR-29a* ACUGAUUUCUUUUGGUGUUCAG hsa-miR-886-5p CGGGUCGGAGUUAGCUCAAGCGG mmu-miR-29b UAGCACCAUUUGAAAUCAGUGUU hsa-πuR-887 GUGAACGGGCGCCAUCCCGAGG ramu miR-29b* GCUGGUUUCAUAUGGUGGUUUA hsa-miR-888 UACUCAAAAAGCUGUCAGUCA mmu-miR-29c UAGCACCAUUUGAAAUCGGUUA hsa miR 888* GACUGACACCUCUUUGGGUGAA mmu miR-29c* UGACCGAUUUCUCCUGGU^QUUC hsa-miR-889 UUAAUAUCGGACAACCAUUGU mmu-miR-300 UAUGCAAGGGCAAGCUCUCUUC hsa-miR-890 UACUUOGAAAGGCAUCAGUUG πuπu mjR-300* UUGAAGAGAGGUUAUCCUUUGU hsa-miR-891a UQCAACGAACCUGAGCCACUGA mmu-miR-301a CAGUGCAAUAGUAUUGUCAAAGC hsa-miR-891b UGCAACUUACCUGAGUCAUUGA mmu-miR 301b CAGUGCAAUGGUAUUGUCAAAGC hsa-miR 892a CACUGUGUCCUUUCUGCGUAG mmu-miR-302a UAAGUGCUUCCAUGUUUUGGUGA hsa-miR-892b CACUGGCUCCUUUCUGGGUAGA mmu miR-302a* ACUUAAACGUGGUUGUACUUGC hsa-miR-9 UCUUUGGUUAUCUAGCUGUAUGA mmu-miR-302b UAAGUGCUUCCAUGUUUUAGUAG hsa miR 9* AUAAAGCUAGAUAACCGAAAGU mtnu-miR-302b* ACUUUAACAUGGGAAUGCUUUCU hsa-mιR-920 GGGGAGCUGUGGAAGCAGUA mmu miR 302c AAGUGCUUCCAUGUUUCAGUGG hsa miR 921 CUAGUGAGGGACAGAACCAGGAUUC mmu-miR-302c* GCUUUAACAUGGGGUUACCUGC hsa-miR-922 GCAGCAGAGAAUAGGACUACGUC mmu-miR-302d UAAGUGCUUCCAUGUUUGAGUGU hsa-miR-923 GUCAGCGGAGGAAAAGAAACU mmu-miR-30a UGUAAACAUCCUCGACUGGAAG

Ssa-rmR-924 AGAGUCUUGUGAUGUCUUGC mmu-miR 30a* CUUUCAGUCGGAUGUUUGCAGC hsa-miR 92a UAUUGCACUUGUCCCGGCCUGU mmu miR 30b UGUAAACAUCCUACACUCAGCU hsa-miR 92a l* AGGUUGGGAUCGGUUGCAAUGCU mmu πuR 30b* CUGGGAUGUGGAUGUUUACGUC hsa miR-92a-2* GGGUGGGGAUUUGUUGCAUUAC mmu πuR-30c UGUAAACAUCCUACACUCUCAGC hsa-miR-92b UAUUGCACUCGUCCCGGCCUCC mmu miR-30c-l* CUGGGAGAGGGUUGUUUACUCC hsa-miR-92b* AGGGACGGGACGCGGUGCAGUG mmυ miR-30e-2* CUGGGAGAAGGCUGUUUACUCU hsa-miR-93 CAAAGUGCUGUUCGUGCAGGUAG mmu miR-30d UGUAAACAUCCCCGACUGGAAG hsa-ttuR-93* ACUGCUGAGCUAGCACUUCCCG mmu-miR-30e UGUAAACAUCCUUGACUGGAAG hsa-miR-933 UGUGCGCAGGGAGACCUCUCCC mmu-miR 3Oe* CUUUCAGUCGGAUGUUUACAGC hsa-miR-934 UGUCUACU ACUGGAGACACUGG mmu πuR-3I AGGCAAGAUGCUGGCAUAGCUG hsa-miR 93S CCAGUUACCGCUUCCC3CUACCGC mmu miR-3 I* UGCUAUGCCAACAUAUUGCCAUC hsa-miR-936 ACAGUAGAGGGAQaAAUCGCAG mmu-miR-32 UAUUGCACAUUACUAAGUUGCA hsa-miR 937 AUCCGCGCUCUGACUCUCUGCC mmu-miR-320 AAAAGCUGGGUUGAGAGGGCGA hsa-miR 938 UGCCCUUAAAGGUGAACCCAGU mmu-mιR-322 CAGCAGCAAUUCAUGUUUUGGA hsa miR-939 UGGGGAGCUGAGGCUCUGGGGGUG mmu-miR 322* AAACAUGAAGCGCUGCAACAC hsa miR 940 AAGGCAGGGCCCCCGCUCCCC minu-πuR-323 3p CACAUUACACGGUCGACCUCU hsa miR-941 CACCCGGCUGUGUGCACAUGUGC mmu-miR 323 5p AGGUGGUCCGUGGCGCGUUCGC hsa miR-942 UCUUCUCUGUUUUGGCCAUGUG mmu miR-324-3p CCACUGCCCCAGGUGCUGCU hsa-miR-943 CUGACUGUUGCCGUCCUCCAG mmu-miR-324-5p CGCAUCCCCUAGGGCAUUGGUGU hsa miR-944 AAAUUAUUGUACAUCGGAUGAG mmu miR-325 UUUAUUGAGCACCUCCUAUCAA hsa-nuR-95 UUCAACGGGUAUUUAUUGAGCA mmu-miR-325* CCUAGUAGGUGCUCAGUAAGUGU hsa-miR-96 UUUOGCACUAGCACAUUUUUGCU mmu-iωR-326 CCUCUGGGCCCUUCCUCCAGU hsa-miR-96* AAUCAUGUGCAGUGCCAAUAUG mmu-imR-327 ACUUGAGGGGCAUGAGGAU hsa-miR-98 UGAGGUAGUAAGUUGUAUUGUU mmu-miR 328 CUGGCCCUCUCUGCCCUUCCGU hsa miR-99a AACCCGUAGAUCCGAUCUUGUG mmu-miR 329 AACACACCCAGCUAACCUUWU hsa-miR-99a* CAAGCUCGCUUCUAUGGGUCUG mmu miR 33 GUGCAUUGUAGUUGCAUUGCA hsa-miR-99b CACCCGUAGAACCGACCUUGCQ mmu-miR-33* CAAUGUUUCCACAGUGCAUCAC hsa-miR-99b* CAAGCUCGUGUCUGUGGGUCCG mmu-miR-330 UCUCUGGGCCUGUGUCUUAGGC aga-bantam UGAGAUCACUUUGAAAGCUGAUU mmu-miR-330* GCAAAGCACAGGGCCUGCAGAGA aga-let-7 UGAGGUAGUUGGUUGUAUAGU mmu-miR-331 -3p GCCCCUGGGCCUAUCCUAGAA aga-miR-1 UGGAAUGUAAAGAAGUAUGGAG mmu-miR-331-5p CUAGGUAUGGUCCCAGGGAUCC aga-miR-10 ACCCUGUAGAUCCGAAUUUGU mmu-miR-335-3p UUUUUCAUUAUUGCUCCUGACC aga-miR-100 AACCCGUAGAUCCGAACUUGUG mmu-miR-335-5p UCAAGAGCAAUAACGAAAAAUGU aga-miR-1174 UCAGAUCUACUUCAUACCCAUG mmu-miR-337-3p UUCAGCUCCUAUAUGAUGCCU aga-miR-1175 UGAGAUUCUACUUCUCCGACUUAA mmu-miR-337-5p GAACGGCGUCAUGCAGGAGUU aga-miR-12 UGAGUAUUACAUCAGGUACUGGU mmu-miR-338-3p UCCAGCAUCAGUGAUUUUGUUG aga-miR-124 UAAGGCACGCGGUGAAUGCCAAG ramu-iπiR-338-5p AACAAUAUCCUGGUGCUGAGUG aga miR-125 UCCCUGAGACCCUAACUUGUGA mmu-πnR-339-3p UGAGCGCCUCGGCGACAGAGCCG aga-miR-133 UUGGUCCCCUUCAACCAGCUGU mmu-miR-339-5p UCCCUGUCCUCCAGGAGCUCACG aga-miR-13b UAUCACAGCCAUUUUGACGAGU mmu-miR-340-3p UCCGUCUCAGUUACUUUAUAGC aga miR-14 UCAGUCUUUUUCUCUCUCCUA mmu-miR-340-5p UUAUAAAGCAAUGAGACUGAUU aga miR-184 UGGACGGAGAACUGAUAAGGG mmu-miR-341 UCGGUCGAUCGGUCGGUCGGU aga miR-2 GCUCAUCAAAGCUGGCUGUGAUA mmu-miR-342-3p UCUCACACAGAAAUCGCACCCGU aga-miR-210 UUGUGCGUGUGACAACGGCUA mmu-miR-342-5p AGGGGUGCUAUCUGUGAUUGAG aga-miR-219 UGAUUGUCCAAACGCAAUUCUUG mmu-miR-343 UCUCCCUUCAUGUGCCCAGA aga miR 263 UGUAAUGGCACUGGAAGAAUUCAC mmu-miR-344 UGAUCUAGCCAAAGCCUGACUGU aga-miR-275 UCAGGUACCUGAAGUAGCGCGCG nunu miR 345 3p CCUGAACUAGGGGUCUGGAGAC aga-miR-276 CAGCGAGGUAUAGAGUUCCUACG mmu-miR-345-5p GCUGACCCCUAGUCCAGUGCUU aga-miR-277 UAAAUGCACUAUCUGGUACGACA mmu-miR-346 UGUCUGCCCGAGUGCCUGCCUCU aga-miR-278 UCGGUGGGACUUUCGUCCGUUU mmu-miR-34a UGGCAGUGUCUUAGCUGGUUGU aga-miR-279 UGACUAGAUCCACACUCAUUAA mmu-miR-34b-3p AAUCACUAACUCCACUGCCAUC aga-πuR-281 UGUCAUGGAAUUGCUCUCUUUAU mmu-πuR-34b-5p AGGCAGUGUAAUUAGCUGAUUGU aga-miR-282 AAUCUAGCCUCUUCUAGGCUUUGUCUGU mmu-nuR-34o AGGCAGUGUAGUUAGCUGAUUGC aga miR-283 UAAAUAUCAGCUGGUAAUUCU mmu-πuR-34c* AAUCACUAACCACACAGCCAGG aga-miR-305 AUUGUACUUCAUCAGGUGCUCUG mmu-nuR-350 UUCACAAAGCCCAUACACUUUC aga-miR-306 UCAGGUACUGGAUGACUCUCAG mmu-DuR-351 UCCCUGAGGAGCCCUUUGAGCCUG aga-miR-307 UCACAACCUCCTJUGAGUGAG mmu-mjR-361 UUAUCAGAAUCUCCAGGGGUAC aga-miR-308 AAUCACAGGAGUAUACUGUGAG mmu-miR-362-3p AACACACCUGUUCAAGGAUUCA aga-miR-315 UUUUGAUUGUUGCUCAGAAAGC mmu-miR-362-5p AAUCCUUGGAACCUAGGUGUGAAU aga-miR-317 UGAACACAUCUGGUGGUAUCUCAGU mmu-miR-363 AAUUGCACGGUAUCCAUCUGUA aga-miR-34 UGGCAGUGUGGUUAGCUGGU mmu-miR-365 UAAUGCCCCUAAAAAUCCUUAU aga-miR-7 UGGAAGACUAGUGAUUUUGUUGU mmu miR-367 AAUUGCACUUUAGCAAUGGUGA aga-miR-79 UAAAGCUAGAUUACCAAAGCAU mmu-miR-369-3p AAUAAUACAUGGUUGAUCUUU aga-miR-8 UAAUACUGUCAGGUAAAGAUGUC πimu-miR-369-5p AGAUCGACCGUGUUAUAUUCGC aga-raiR-92a UAUUGCACUUGUCCCGGCCUAU mmu-m]R-370 GCCUGCUGGGGUGGAACCUGGU aga-miR-92b AAUUGCACUUGUCCCGGCCUGC mmu-miR-374 AUAUAAUACAACCUGCUAAGUG aga-miR-989 UGUGAUGUGACGUAGUGGUAC mmu-miR-374* GGUUGUAUUAUCAUUGUCCGAG aga-πuR-996 UGACUAGAUUACAUGCUCGUCU mmu-πuR-375 UUUGUUCGUUCGGCUCGCGUGA aga-miR-9a UCUUUGGUUAUCUAGCUGUAUGA mmu-miR-376a AUCGUAGAGGAAAAUCCACGU aga miR-9b ACUUUGGUGAUUUUAGCUGUAUG iranu-miR-376a* GGUAGAUUCUCCUUCUAUGAGU aga-miR-9c UCUUUGGUAUUCUAGCUGUAGA πunu-miR-376b AUCAUAGAGGAACAUCCACUU aga-miR-iab-4 ACGUAUACUGAAUGUAUCCUGA mmu-πuR-376b* GUGGAUAUUCCUUCUAUGGUUA age-miR-100 AACCCGUAGAUCCGAACUUGUG mmu-miR-376c AACAUAGAGGAAAUUUCACGU age-miR-101 UACAGUACUGUGAUAACUGAAG mmu-miR-376c* GUGGAUAUUCCUUCUAUGUUUA age-miR-103 AGCAGCAUUGUACAGGGCUAUGA mmu-miR-377 AUCACACAAAGGCAACUUUUGU age-miR-106a AAAAGUGCUUACAGUGCAGGUAGC mmu-miR-378 ACUGGACUUGGAGUCAGAAGG age-miR-106b UAAAGUGCUGACAGUGCAGAU mmu-miR-378* CUCCUGACUCCAGGUCCUGUGU age-miR-10a UACCCUGUAGAUCCGAAUUUGUG mmu miR-379 UGGUAGACUAUGGAACGUAGG age-πuR-124a UUAAGGCACGCGGUGAAUGCCA mmu-miR-380-3p UAUGUAGUAUGGUCCACAUCUU age-miR-125b UCCCUGAGACCCUAACUUGUGA mmu-miR-380-5p AUGGUUGACCAUAGAACAUGCG age miR-127 UCGGAUCCGUCUGAGCUUGGCU mmu-miR-381 UAUACAAGGGCAAGCUCUCUGU age-raiR-128 UCACAGUGAACCGGUCUCUUUU mmu-miR-382 GAAGUUGUUCGUGGUGGAUUCG age-miR-133a UUGGUCCCCUUCAACCAGCUGU mmu-miR 382* UCAUUCACGGACAACACUUUUU age-miR-135 UAUGGCUUUUUAUUCCUAUGUGA mmu-miR-383 AGAUCAGAAGGUGACUGUGGCU age-miR-15a UAGCAGCACAUAAUGGUUUGUG mmu-miR-384-3p AUUCCUAGAAAUUGUUCACAAU age-miR-15b UAGCAGCACAUCAUGGUUUACA πunu-miR-384-5p UGUAAACAAUUCCUAGGCAAUGU age-mjR-16 UAGCAGCACGUAAAUAUUGGCG mmu-miR-409-3p GAAUGUUGCUCGGUGAACCCCU age-rruR-17-3p ACUGCAGUGAAGGCACUUGU mmu-miR-409-5p AGGUUACCCGAGCAACUUUGCAU age-miR-17-5p CAAAGUGCUUACAGUGCAGGUAGU mmu-miR-410 AAUAUAACACAGAUGGCCUGU age-miR-18 UAAGGUGCAUCUAGUGCAGAUA mmu-miR-41 1 UAGUAGACCGUAUAGCGUACG age-miR-194 UGUAACAGCAACUCCAUGUGGA mmu-miR-41 1 * UAUGUAACACGGUCCACUAACC age-miR-196 UAGGUAGUUUCAUGUUGUUGGG mmu-miR-412 UUCACCUGGUCCACUAGCCG age-miR-197 UUCACCACCUUCUCCACCCAGC mmu-miR-421 AUCAACAGACAUUAAUUGGGCGC age-miR-198 GGUCCAGAGGGGAGCUAGG mmu-miR-423-3p AGCUCGGUCUGAGGCCCCUCAGU age-miR-19a UGUGCAAAUCUAUGCAAAACUGA mmu-πuR-423-5p UGAGGGGCAGAGAGCGAGACUUU age-miR-19b UGUGCAAAUCCAUGCAAAACUGA mmu-miR-425 AAUGACACGAUCACUCCCGUUGA age-miR-20 UAAAGUGCUUAUAGUGCAGGUA mmu-imR-425* AUCGGGAAUGUCGUGUCCGCC age-miR-205 UCCUUCAUUCCACCGGAGUCUG mmu-miR-429 UAAUACUGUCUGGUAAUGCCGU age-miR-21 UAGCUUAUCAGACUGAUGUUGA πumi-miR-431 UGUCUUGCAGGCCGUCAUGCA age-miR-214 ACAGCAGGCACAGACAGGCAG mmu-miR-431* CAGGUCGUCUUGCAGGGCUUCU age miR-218 UUGUGCUUGAUCUAACCAUGU mmu-miR-433 AUCAUGAUGGGCUCCUCGGUGU age-miR-22 AAGCUGCCAGUUGAAGAACUGU mmu-πuR-433* UACGGUGAGCCUGUCAUUAUUC age-miR-222 AGCUACAUCUGGCUACUGGGUCUC mmu-miR-434-3p UUUGAACCAUCACUCGACUCCU age-miR-23a AUCACAUUGCCAGGGAUUUCC mmu-πuR-434-5p GCUCGACUCAUGGUUUGAACCA age-nuR-27a UUCACAQUGGCUAAGUUCCGCC mmu-miR-448 UUGCAUAUGUAGGAUGUCCCAU age-miR-28 AAGGAGCUCACAGUCUAUUGAG mmu-miR-449a UGGCAGUGUAUUGUUAGCUGGU age-nuR-29a CUAGCACCAUCUGAAAUCGGUU mmu-miR-449b AGGCAGUGUUGUUAGCUGGC age-nuR-29b UAGCACCAUUUGAAAUCAGU mmu-miR-449o AGGCAGUGCAUUGCUAGCUGG age-miR-30b UGUAAACAUCCUACACUCAGC mmu-miR-450a-3p AUUGGGGAUGCUUUGCAUUCAU age-πuR-34a UGGCAGUGUCUUAGCUGGUUGU mmu-miR-450a-5p UUUUGCGAUGUGUUCCUAAUAU age-miR-506 AAUGGCGCCCUUCUGAGUAGA mmu-miR-450b-3p AUUGGGAACAUUUUGCAUGCAU age-miR-507 UUUGGCACUUUUUAGAGUGAA mmu-miR-450b-5p UUUUGCAGUAUGUUCCUGAAUA age-mJR-508 CGAUUGUCACCUUUUUGAGUAGA mmu-miR-451 AAACCGUUACCAUUACUGAGUU age-πuR-509a UGAUUGACACGUCUGCAGGUAGA mmu-miR-452 UGUUUGCAGAGGAAACUGAGAC age-miR-509b UGAUUGACACGUCUGCAGAUAGA mmu-miR-453 AGGUUGCCUCAUAGUGAGCUUGCA age-miR-510 UACUCCAGAGAGUAGCAAUCACG mmu-miR-455 GCAGUCCACGGGCAUAUACAC age-miR-513a UUCACAAGGAGGUGUCAUUCAU mmu-miR-455* UAUGUGCCUUUGGACUACAUCG age-miR-513b UUCACAAGGAGCUGUCAUUCAU mmu-miR-463 UGAUAGACACCAUAUAAGGUAG age-πuR-513c UUCUCAAGAAGGUGUCAUUCAU mmu-miR-463* UACCUAAUUUGUUGUCCAUCAU agE-miR-513d UUCACAACGAGGUGUCAUUUAU mmu-miR-464 UACCAAGUUUAUUCUGUGAGAUA age-miR-513e UUACAAGAAGGUGCCAUUCAU mmu-miR-465a-3p GAUCAGGGCCUUUCUAAGUAGA age-miR-514 AUUGACACUUUUGUGAGUAG mmu-miR-465a-5p UAUUUAGAAUGGCACUGAUGUGA agε-miR-9 UCUUUGGUUAUCUAGCUGUAUGA mmu-miR-465b-3p GAUCAGGGCCUUUCUAAGUAGA age-miR-92 UAUUGCACUUGUCCCGGCCUGU mmu-miR-465b-5p UAUUUAGAAUGGUGCUGAUCUG age-miR-93 AAAGUGCUGUUCGUGCAGGUAG mmu-miR-465c-3p GAUCAGGGCCUUUCUAAGUAGA age-miR-98 UGAGGUAGUAAGUUGUAUUGUU mmu-miR-465c-5p UAUUUAGAAUGGCGCUGAUCUG ame-bantam UGAGAUCAUUGUGAAAGCUGAUU mmu-miR-466a-3p UAUACAUACACGCACACAUAAGA ame-)et-7 UGAGGUAGUAGGUUGUAUAGU mmu-miR-466a-5p UAUGUGUGUGUACAUGUACAUA ame-miR-1 UGGAAUGUAAAGAAGUAUGGAG mmu-miR-466b-3-3p AAUACAUACACGCACACAUAAGA ame-miR-10 ACCCUGUAGAUCCGAAUUUGU mmu-miR-466b-3p UAUACAUACACGCACACAUAAGA ame-miR-100 AACCCGUAGAUCCGAACUUGUG mmu-miR-466b-5p GAUGUGUGUGUACAUGUACAUG ame-miR-12 UGAGUAUUACAUCAGGUACUGGU mmu-miR-466c-3p UAUACAUACACGCACACAUAAGA amβ-miR-124 UAAGGCACGCGGUGAAUGCCAAG mmu-miR-466c-5p GAUGUGUGUGUGCAUGUACAUA ame-πuR-125 CCCCUGAGACCCUAACUUGUGA mmu-miR-466d-3p UAUACAUACACGCACACAUAG ame-miR-133 UUGGUCCCCUUCAACCAGCUGU mmu-miR-466d-5p UGUGUGUGCGUACAUGUACAUG ame-miR-137 UUAUUGCUUGAGAAUACACGUA mmu-miR-466e-3p UAUACAUACACGCACACAUAAGA ame-miR-13a UAUCACAGCCAUUUUGAUGAG mmu-miR-466e-5p GAUGUGUGUGUACAUGUACAUA ame-miR-14 UCAGUCUUUUUCUCUCUCCUA mmu-miR-466f ACGUGUGUGUGCAUGUGCAUGU ame-miR-184 UGGACGGAGAACUGAUAAGGGC mmu-miR-466f-3p CAUACACACACACAUACACAC ame-miR-190 AGAUAUGUUUGAUAUUCUUGGUUGUU mmu-miR-466f-5p UACGUGUGUGUGCAUGUGCAUG ame-miR-2 UAUCACAGCCAGCUUUGAUGAGC mmu-miR-466g AUACAGACACAUGCACACACA ame-miR-210 UUGUGCGUGUGACAGCGGCUA mmu-miR-466h UGUGUGCAUGUGCUUGUGUGUA ame-miR-219 UGAUUGUCCAAACGCAAUUCUUG πunu-miR-466i AUACACACACACAUACACACUA ame-miR-263 GUAAAUGGCACUGGAAGAAUUCAC mmu-miR-466j UGUGUGCAUGUGCAUGUGUGUAA atne-miR-275 UCAGGUACCUGAAGUAGCGCGCG mmu-miR-466k UGUGUGUGUACAUGUACAUGUGA ame-miR-276 UAGGAACUUCAUACCGUGCUCU mmu-miR-4661 UAUAAAUACAUGCACACAUAUU ame-miR-277 UAAAUGCACUAUCUGGUACGACA mmu-miR-467a UAAGUGCCUGCAUGUAUAUGCG ame-miR-278 UCGGUGGGACUUUCGUCCGUUU mmu-miR-467a* AUAUACAUACACACACCUACAC ame-miR-279 UGACUAGAUCCACACUCAUUAA mmu-miR-467b GUAAGUGCCUGCAUGUAUAUG ame-miR-281 UGUCAUGGAGUUGCUCUCUUUGU mmu-miR-467b* AUAUACAUACACACACCAACAC ame-miR-282 GAUUUAGCCUCUCCUAGGCUUUGUCUGU mmu-imR-467c UAAGUGCGUGCAUGUAUAUGUG ame-miR-283 AAAUAUCAGCUGGUAAUUCU mmu-miR-467d UAAGUGCGCGCAUGUAUAUGCG ame-miR-29b UAGCACCAUUUGAAAUCAGU mmu-miR-467d* AUAUACAUACACACACCUACAC ame-miR-305 AUUGUACUUCAUCAGGUGCUCUG mmu-miR-467e AUAAGUGUGAGCAUGUAUAUGU amc-miR-315 UUUUGAUUGUUGCUCAGAAAGC mimi-miR-467e* AUAUACAUACACACACCUAUAU ame-miR-317 UGAACACAGCUGGUGGUAUCUCAGU mmu-miR-467f AUAUACACACACACACCUACA ame-miR-31a GGCAAGAUGUCGGCAUAGCUGA mmu-miR-467g UAUACAUACACACACAUAUAU ame-miR-33 GUGCAUUGUAGUUGCAUUG mmu-miR-467h AUAAGUGUGUGCAUGUAUAUGU ame-miR-34 UGGCAGUGUUGUUAGCUGGUUG mmu-miR-468 UAUGACUGAUGUGCGUGUGUCUG ame-miR-375 UUUGUUCGUUCGGCUCGAGUUA minu-miR-469 UGCCUCUUUCAUUGAUCUUGGUGUCC ame-miR-7 UGGAAGACUAGUGAUUUUGUUGU mmu-miR-470 UUCUUGGACUGGCACUGGUGAGU ame-miR-71 UGAAAGACAUGGGUAGUGA mmu-miR-470* AACCAGUACCUUUCUGAGAAGA ame-miR-79 UAAAGCUAGAUUACCAAAGCA mmu-miR-471 UACGUAGUAUAGUGCUUUUCAC ame-miR-8 UAAUACUGUCAGGUAAAGAUGUC mmu-miR-483 AAGACGGGAGAAGAGAAGGGAG ame-miR-87 GUGAGCAAAGUUUCAGGUGU mmu-miR-483* UCACUCCUCCCCUCCCGUCUU ame-miR-925 AGGGAUUCGGUUUUGUAACAUUCGC mmu-mιR-484 UCAGGCUCAGUCCCCUCCCGAU ame-miR-926 GCGGCCAGGUUGGCGGUGUACGA mmu-miR-485 AGAGGCUGGCCGUGAUGAAUUC ame-πuR-927 UUUUAGAAUUCCUACGCUUUACC mmu-miR-485* AGUCAUACACGGCUCUCCUCUC ame-miR-928 CUGGCUGUGGAAGCUGGCGAA mmu-miR-4S6 UCCUGUACUGAGCUGCCCCGAG ams-miR-929 AUUGACUCUAGUAGGGAGUCC mmu-miR-487b AAUCGUACAGGGUCAUCCACUU ame-miR-92a AUUGCACUUGUCCCGGCCUAU mmu-miR-488 UUGAAAGGCUGUUUCUUGGUC ame-miR-930 CAGGUGAAAAUCUGGUUCCAGA mmu-miR-488* CCCAGAUAAUAGCACUCUCAA ame-miR-931 GCCGUCACCCAGUCCUGCAGCA mmu-miR-489 AAUGACACCACAUAUAUGGCAGC ame-miR-932 UCAAUUCCGUAGUGCAUUGCAG mmu-miR-490 CAACCUGGAGGACUCCAUGCUG ame-miR-9a UCUUUGGUUAUCUAGCUGUAUGA mmu-miR-491 AGUGGGGAACCCUUCCAUGAGG ame-miR-9b GCUUUGGUAAUCUAGCUUUAUGA mmu-miR-493 UGAAGGUCCUACUGUGUGCCAGG ame-miR-iab-4 ACGUAUACUGAAUGUAUCCUGA mmu-miR-494 UGAAACAUACACGGGAAACCUC bmo-let-7 UGAGGUAGUAGGUUGUAUAGU mmu-miR-495 AAACAAACAUGGUGCACUUCUU bmo-miR-1 UGGAAUGUAAAGAAGUAUGGAG mmu-miR-496 UGAGUAUUACAUGGCCAAUCUC bmo-miR-10 ACCCUGUAGAUCCGAAUUUGU mmu-miR-497 CAGCAGCACACUGUGGUUUGUA bmo-miR-124 UAAGGCACGCGGUGAAUGCCAAG mmu-miR-499 UUAAGACUUGCAGUGAUGUUU bmo-miR-14 UCAGUCUUUUUCUCUCUCCUA πunu-πuR-500 AAUGCACCUGGGCAAGGGUUCA bmo miR-263a AAUGGCACUGGAAGAAUUCAC mmu-miR-501-3p AAUGCACCCGGGCAAGGAUUUG bmo-miR-263b CUUGGCACUGGGAGAAUUCAC mmu-πuR-501-5p AAUCCUUUGUCCCUGGGUGAAA bmo-miR-275 UCAGGUACCUGAAGUAGCGCGCG mmu-πuR-503 UAGCAGCGGGAACAGUACUGCAG bmo raiR-276 AGCGAGGUAUAGAGUUCCUACG mmu-πuR-503* GAGUAUUGUUUCCACUGCCUGG bmo miR-277 UAAAUGCACUAUCUGGUACGACA mmu miR-504 AGACCCUGGUCUGCACUCUAUC bmo miR-279 UGACUAGAUCCACACUCAU mmu-miR-505 CGUCAACACUUGCUGGUUUUCU bmo miR-282 ACCUAGCCUCUCCUUGGCUUUGUCUGU mmu-πuR-509-3p UGAUUGACAUUUCUGUAAUGG bmo miR-283 UAAAUAUCAGCUGGUAAUUCU mmu-miR-509-5p UACUCCAGAAUGUGGCAAUCAU bmo-miR-30S AUUGUACUUCAUCAGGUGCUCUG mmu-miR-511 AUGCCUUUUGCUCUGCACUC A bmo-miR-307 UCACAACCUCCUUGAGUGAG mmu-miR-532-3p CCUCCCACACCCAAGGCUUGCA bmo miR-31 GGCAAGAAGUCGGCAUAGCUG mmu-miR-532-5p CAUGCCUUGAGUGUAGGACCGU bmo-miR-34 UGGCAGUGUGGUUAGCUGGUUG mmu miR 539 GGAGAAAUUAUCCUUGGUGUGU bmo miR-7 UGGAAGACUAGUGAUUUUGUUGU mmu-miR-540-3p AGGUCAGAGGUCGAUCCUGG bmo-miR-71 UGAAAGACAUGGGUAGUGA mmu-miR-540-5p CAAGGGUCACCCUCUGACUCUGU bmo miR-8 UAAUACUGUCAGGUAAAGAUGUC mmu-miR-541 AAGGGAUUCUGAUGUUGGUCAC ACU bmo miR-9 UCUUUGGUUAUCUAGCUGUAUGA mmu-miR-S42-3p UGUGACAGAUUGAUAACUGAAA bta-let-7a UGAGGUAGUAGGUUGUAUAGUU mmu-mιR-542-5p CUCGGGGAUCAUCAUGUCACGA bta-let-7a* CUAUACAAUCUACUGUCUUUC mmu-miR-543 AAACAUUCGCGGUGCACUUCUU bta-let-7b UGAGGUAGUAGGUUGUGUGGUU mmu-miR 544 AUUCUGCAUUUUUAGCAAGCUC bta-let-7c UGAGGUAGUAGGUUGUAUGGUU mmu miR-546 AUGGUGGCACGGAGUC bta-let-7d AGAGGUAGUAGGtJUGCAUAGUU mmu-miR 547 CUUGGUACAUCUUUGAGUGAG bta-let-7e UGAGGUAGGAGGUUGUAUAGU mmu miR 55Ib GCGACCCAUACUUGGUUUCAG bta-let-7f UGAGGUAGUAGAUUGUAUAGUU mmu miR-568 AUGUAUAAAUGUAUACACAC bta let-7g UGAGGUAGUAGUUUGUACAGUU mmu miR 574 3p CACGCUCAUGCACACACCCACA bta-let-7i UGAGGUAGUAGUUUGUGCUGUU mmu miR-574-5p UGAGUGUGUGUGUGUGAGUGUGU bta-miR-101 UACAGUACUGUGAUAACUGAA mmu-miR-582-3p CCUGUUGAACAACUGAACCCAA bta-miR-103 AGCAGCAUUGUACAGGGCUAUGA mmu-miR-582-5p UACAGUUGUUCAACCAGUUACU bta-miR-106 AAAAGUGCUUACAGUGCAGGUA mmu miR-590-3p UAAUUUUAUGUAUAAGCUAGU bta-πuR-107 AGC AGCAUUGUAC AGGGCUAUC mmu-miR-590-5p GAGCUUAUUCAUAAAAGUGCAG bta-miR-lOa UACCCUGUAGAUCCGAAUUUGUG mmu-miR-592 AUUGUGUCAAUAUGCGAUGAUGU bta-miR-lOb UACCCUGUAGAACCGAAUUUGUG mmu-miR-598 UACGUCAUCGUCGUCAUCGUUA bta miR-122 UGGAGUGUGACAAUGGUGUUUG mmu-miR-615-3p UCCGAGCCUGGGUCUCCCUCUU bta-miR-124a UUAAGGCACGCGGUGAAUGCCAA mmu-miR-615-5p GGGGGUCCCCGGUGCUCGGAUC bta-miR-125a UCCCUGAGACCCUUUAACCUGUG mmu-miR-652 AAUGGCGCCACUAGGGUUGUG bta-miR-125b UCCCUGAGACCCUAACUUGUGA mmu-miR-653 GUGUUGAAACAAUCUCUACUG bta-miR-126 CGUACCGUGAGUAAUAAUGCG mmu-miR-654-3p UAUGUCUGCUGACCAUCACCUU bta-miR-126* CAUUAUUACUUUUGGUACGCG mmu-miR-654-5p UGGUAAGCUGCAGAACAUGUGU bta-miR-127 UCGGAUCCGUCUGAGCUUGGCU mmu-miR-665 ACCAGGAGGCUGAGGUCCCU bta-miR 128 UCACAGUGAACCGGUCUCUUUU mmu-miR-666-3p GGCUGCAGCGUGAUCGCCUGCU bta-miR 132 UAACAGUCUACAGCCAUGGUCG mmu-miR-666-5p AGCGGGCACAGCUGUGAGAGCC bta-miR-138 AGCUGGUGUUGUGAAUCAGGCCG mmu-mιR-667 UGACACCUGCCACCCAGCCCAAG bta-miR 139 UCUACAGUGCACGUC3UCUCCAGU mmu-miR-668 UGUCACUCGGCUCGGCCCACUACC bta miR 140 UACCAC AGGGUAGAACCACGGA mmu miR-669a AGUUGUGUGUGCAUGUUCAUGU bta miR-142 CAUAAAGUAGAAAGCACUAC mrau-miR-669b AGUUUUGUGUGCAUGUGCAUGU bta miR-142* AGUGUUUCCUACUUUAUGGAUG mmu-miR-669o AUAGUUGUGUGUGGAUGUGUGU bta-miR-145 GUCCAGUUUUCCCAGGAAUCCCU mmu-miR-669d ACUUGUGUGUGCAUGUAUAUGU bta-miR 148a UCAGUGCACUACAGAACUUUGU mmu-miR-669e UGUCUUGUGUGUGCAUGUUCAU bta πuR-I48b UCAGUGCAUCACAGAACUUUGU mmu-miR-669f CAUAUACAUACACACACACGUAU bta-miR-150 UCUCCCAACCCUUGUACCAGUGU mmu-miR-669g UGCAUUGUAUGUGUUGACAUGAU bta-miR-151 CUAGACUGAAGCUCCUUGAGG mmu-miR-669h 3p UAUGCAUAUACACACAUGCACA bta-miR-151* UCGAGGAGCUCACAGUCUAGU mmu miR-669h-5p AUGCAUGGGUGUAUAGUUGAGUGC bta-miR-15a UAGCAGCACAUAAUGGUUUGU mmu-miR-6691 UGCAUAUACACACAUGCAUAC bta-miR-I5b UAGCAGCACAUCAUGGUUUACA mmu-πuR-669j UGCAUAUACUCACAUGCAAACA bta-miR-16 UAGCAGCACGUAAAUAUUGGC mmu-miR-669k UAUGCAUAUACACGCAUGCAA bta-miR-17 3p ACUGCAGUGAAGGCACUUGU mmu-miR-670 AUCCCUGAGUGUAUGUGGUGAA bta miR-17-5p CAAAGUGCUUACAGUGCAGGUAGU mmu-miR-671 3p UCCGGUUCUCAGGGCUCCACC bta-miR-181 a AACAUUCAACGCUGUCGGUGAGUU mmu rniR 671-5p AGGAAGCCCUGGAGGGGCUGGAG bta-raiR-181b AACAUUCAUUGCUGUCGGUGGGUUU mmu-miR 672 UGAGGUUGGUGUACUGUGUGUGA bta-miR-181c AACAUUCAACCUGUCGGUGAGUUU mmu πuR 673-3p UCCGGGGCUGAGUUCUGUGCACC bta-miR-186 CAAAGAAUUCUCCUUUUGGGCU mmu miR 673-5p CUCACAGCUCUGGUCCUUGGAG bta-miR-18a UAAGGUGCAUCUAGUGCAGAUA mmu-m₁R-674 GCACUGAGAUGGGAGUGGUGUA bta-miR-18b UAAGGUGCAUCUAGUGCAGUUA mmu-miR-674* CACAGCUCCCAUCUCAGAACAA bta miR-191 CAACGGAAUCCCAAAAGCAGCUG mmu-miR-67S-3p CUGUAUGCCCUAACCGCUCAGU bta-miR-192 CUGACCUAUGAAUUGACAGCCAG mmu-miR-675-5p UGGUGCGGAAAGGGCCCACAGU bta-miR-193a AACUGGCCUACAAAGUCCCAGU mmu-miR-676 CCGUCCUGAGGUUGUUGAGCU bta-miR-193a* UGGGUCUUUGCGGGCGAGAUGA mmu-miR-676* ACUCUACAACCUUAGGACUUGC bta-miR-195 UAGCAGCACAGAAAU AUUGGCA mmu πuR 677 UUCAGUGAUGAUUAGCUUCUGA bta-miR-199a-3p ACAGUAGUCUGCACAUUGGUUA mmu-miR-678 GUCUCGGUGCAAGGACUGGAGG bta-miR-199a-5p CCCAGUGUUCAGACUACCUGUU mmu-πuR-679 GGACUGUGAGGUGACUCUUGGU bta-miR-199b CCCAGUGUUUAGACUAUCUGUUC mmu-miR-680 GGGCAUCUGCUGACAUGGGGG bta miR-19a UGUGCAAAUCUAUGCAAAACUGA mmu-miR-681 CAGCCUCGCUGGCAGGCAGCU bta-miR-19b UGUGC AAAUCCAUGC AAAACUG A mmu-miR-682 CUGCAGUCACAGUGAAGUCUG bta-miR-200a UAACACUGUCUGGUAACGAUGUU mmu-miR-683 CCUGCUGUAAGCUGUGUCCUC bta-miR-200b UAAUACUGCCUGGUAAUGAUG mmu-miR-684 AGUUUUCCCUUCAAGUCAA bta-miR 20Oo UAAUACUGCCGGGUAAUGAUGGA mmu-miR 685 UCAAUGGCUGAGGUGAGGCAC bta-miR-204 UUCCCUUUGUCAUCCUAUGCCU mmu imR 686 AUUGCUUCCCAGACGGUGAAGA bta-miR-205 UCCUUCAUUCCACCGGAGUCUG mmu-miR-687 CUAUCCUGGAAUGCAGCAAUGA bta-miR-20a UAAAGUGCUUAUAGUGCAGGUAG mmu-miR-688 UCGCAGGCGACUACUUAUUC bta-miR-20b CAAAGUGCUCACAGUGCAGGUA mimi-miR-689 CGUCCCCGCUCGGCGGGGUCC bta-raiR-21 UAGCUUAUCAGACUGAUGUUGACU mmu-miR-690 AAAGGCUAGGCUCACAACCAAA bta-miR-21* AACAGC AGUCGAUGGGCUGUCU mπra-miR-691 AUUCCUGAAGAGAGGCAGAAAA bta-miR-210 ACUGUGCGUGUGACAGCGGCUGA minu-miR-692 AUCUCUUUGAGCGCCUCACUC bta-miR-214 ACAGCAGGCACAGACAGGCAGU nunu-miR-693-3p GCAGCUUUCAGAUGUGGCUGUAA bta-miR-215 AUGACCU AUGAAUUGAC AGAC A mmu-πuR-693-5p CAGCCACAUCCGAAAGUUUUC bta-miR-218 UUGUGCUUGAUCUAACCAUGU mmu-miR-694 CUGAAAAUGUUGCCUGAAG bta-miR-221 AGCUACAUUGUCUGCUGGGUUU mmu-miR-695 AGAUUGGGCAUAGGUGACUGAA bta-miR-222 AGCUACAUCUGGCUACUGGGU mmu-miR-696 GCGUGUGCUUGCUGUGGG bta-miR-22-5p AGUUCUUCAGUGGCAAGCUUUA πnnu-miR-697 AACAUCCUGGUCCUGUGGAGA bta-miR-23a AUCACAUUGCCAGGGAUUUCCA mmu-miR-698 CAUUCUCGUUUCCUUCCCU bta-miR-23b AUCACAUUGCCAGGGAUUACCAC mmu-miR-699 AGGCAGUGCGACCUGGCUCG bta-miR-24 UGGCUCAGUUCAGCAGGAACAG mmu-miR-700 CACGCGGGAACCGAGUCCACC bta-miR-25 CAUUGCACUUGUCUCGGUCUGA mmu-miR-701 UUAGCCGCUGAAAUAGAUGGA bta-miR-26a UUCAAGUAAUCCAGGAUAGGCU mmu-miR-702 UGCCCACCCUUUACCCCGCUC bta-miR-26b UUCAAGUAAUUCAGGAUAGGUU mmu-miR-703 AAAACCUUCAGAAGGAAAGAA bta-miR-27a UUCACAGUGGCUAAGUUCCG πunu-miR-704 AGACAUGUGCUCUGCUCCUAG bta-miR-27b UUCACAGUGGCUAAGUUCUGC πunu-miR-705 GGUGGGAGGUGGGGUGGGCA bta-miR-29a CUAGCACCAUCUGAAAUCGGUUA πunu-miR-706 AGAGAAACCCUGUCUCAAAAAA bta-miR-29b UAGCACCAUUUGAAAUCAGUGUUU πunu-miR-707 CAGUCAUGCCGCUUGCCUACG bta-miR-29c UAGCACCAUUUGAAAUCGGUUA πunu-miR-708 AAGGAGCUUACAAUCUAGCUGGG bta-miR-3 Oa-Sp UGUAAAC AUCCUCGACUGGAAGCU πunu-miR-708* CAACUAGACUGUGAGCUUCUAG bta-miR-30b UGUAAACAUCCUACACUCAGCU mmu-miR-709 GGAGGCAGAGGCAGGAGGA bta-miR-30o UGUAAACAUCCUACACUCUCAGC ramu-miR-710 CCAAGUCUUGGGGAGAGUUGAG bta-miR-30d UGUAAACAUCCCCGACUGGAAGCU mmu-miR-711 GGGACCCGGGGAGAGAUGUAAG bta-miR-30e-5p UGUAAACAUCCUUGACUGGAAGCU mmu-miR-712 CUCCUUCACCCGGGCGGUACC bta-imR-31 AGGCAAGAUGCUGQCAUAGCU πunu-miR-712* UGCGAGUCACCCCCGGGUGUUG bta-miR-320 AAAAGCUGGGUUGAGAGGGCGA mmu miR 713 UGCACUGAAGGCACACAGC bta-miR-33 ] GCCCCUGGGCCUAUCCUAGAA mmu-miR-714 CGACGAGGGCCGGUCGGUCGC bta-miR-342 UCUCACACAGAAAUCGCACCCAUCU mmu-miR-715 CUCCGUGCACACCCCCGCGUG bta-miR-345 GCUGACUCCUAGUCCAGUGCU mmu-miR-717 CUCAGACAGAGAUACCUUCUCU bta-miR-34a UGGCAGUGUCUUAGCUGGUUGU mmu-πuR-718 CUUCCGCCCGGCCGGGUGUCG bta-miR-34b AGGCAGUGUAAUUAGCUGAUUG mmu-miR-719 AUCUCGGCUACAGAAAAAUGUU bta-πuR-34c AGGCAGUGUAGUUAGCUGAUUG mmu-miR-720 AUCUCGCUGGGGCCUCCA bta-miR-361 UUAUCAGAAUCUCCAGGGGUAC mmu-miR-721 CAGUGCAAUUAAAAGGGGGAA bta-miR-363 AUUGCACGGUAUCCAUCUGCG mmu-miR-741 UGAGAGAUGCCAUUCUAUGUAGA bta-miR-365 UAAUGCCCCUAAAAAUCCUUAU mmu-miR-742 GAAAGCCACCAUGCUGGGUAAA bta-miR-369-3p AAUAAUACAUGGUUGAUCUUU mmu-miR-742* UACUCACAUGGUUGCUAAUCA bta-miR-369-5p AUCGACCGUGUUAUAUUCGC mmu-miR-743a GAAAGACACCAAGCUGAGUAGA bta-raiR-374 UUAUAAUACAACCUGAUAAGUG mmu-miR-743b-3p GAAAGACAUCAUGCUGAAUAGA bta-miR-38O-3p UAUGUAAUGUGGUCCACGUCU mmu-miR-743b-5p UGUUCAGACUGGUGUCCAUCA bta-miR-380-5p UGGUUGACC AUAGAACAUGCGC mmu-miR-744 UGCGGGGCUAGGGCUAACAGCA bta-πuR-423 AAGCUCGGUCUGAGGCCCCUCAGU mmu-miR-744* CUGUUGCCACUAACCUCAACCU bta-miR-425-3p AUCGGGAAUGUCGUGUCCGCCC mmu-miR-758 UUUGUGACCUGGUCCACUA bta-miR-425-5p AUGACACGAUCACUCCCGUUGA mmu-miR-759 GCAGAGUGCAAACAAUUUUGAC bta-miR-450 UUUUGCGAUGUGUUCCUAAUAU mmu-miR-760 CGGCUCUGGGUCUGUGGGGA bta-miR-455 UAUGUGCCUUUGGACUACAUC iπinu-miR-761 GCAGCAGGGUGAAACUGACACA bta miR-455* GCAGUCCAUGGGCAUAUACACU mmu-miR-762 GGGGCUGGGGCCGGGACAGAGC bta-miR-484 UCAGGCUCAGUCCCCUCCCGAU mrau-miR-763 CCAGCUGGGAAGAACCAGUGGC bta-miR-487a AAUCAUAC AGGGAC AUCCAGU nraiu-miR-764-3p AGGAGGCCAUAGUGGCAACUGU bta-miR-487b AAUCGUACAGGGUCAUCCACUU mimi-miR-764-5p GGUGCUCACAUGUCCUCCU bta-imR-497 CAGCAGCACACUGUGGUUUGUA mmu-miR-770-3p CGUGGGCCUGACGUGGAGCUGG bta-miR-499 UUAAGACUUGCAGUGAUGUUU mmu-miR-770-5p AGCACCACGUGUCUGGGCCACG bta-miR-532 CAUGCCUUGAGUGUAGGACCGU mmu-miR-7a UGGAAGACUAGUGAUUUUGUUGU bta-miR-545 AUCAACAAACAUUUAUUGUGUG mmu-miR-7a* CAACAAAUCACAGUCUGCCAUA bta-nuR-545* UCAGUAAAUGUUUAUUGGAUG mmu-miR-7b UGGAAGACUUGUGAUUUUGUUGU bta-miR-660 UACCCAUUGCAUAUCGGAGCUG mmu-miR-802 UCAGUAACAAAGAUUCAUCCUU bta-iruR-7 UGGAAGACUAGUGAUUUUGUUGUU mmu-miR-804 UGUGAGUUGUUCCUCACCUGGA bta-miR-92 UAUUGCACUUGUCCCGGCCUGU tranu-miR-805 GAAUUGAUCAGGACAUAGGG bta-miR-93 CAAAGUGCUGUUCGUGCAGGUA mmu-miR-871 UAUUCAGAUUAGUGCCAGUCAUG bta-miR-98 UGAGGUAGUAAGUUGUAUUGUU mmu-miR-872 AAGGUUACUUGUUAGUUCAGG bta-miR-99a AACCCGUAGAUCCGAUCUUGU mmu-miR-872* UGAACUAUUGCAGUAGCCUCCU bta-miR-99b CACCCGUAGAACCGACCUUGCG mmu-miR-873 GCAGGAACUUGUGAGUCUCCU obr-let-7 UGAGGUAGUAGGUUGUAUAGUU mmu-miR-874 CUGCCCUGGCCCGAGGGACCGA cbr-Iin-4 UCCCUGAGACCUCAAGUGUGA mmu-miR-875-3p CCUGAAAAUACUGAGGCUAUG cbr-lsy-6 UUUUGUAUGAGACGCAUUCCG mmu-raiR-875-5p UAUACCUCAGUUUUAUCAGGUG cbr-miR-1 UGGAAUGUAAAGAAGUAUGUA mmu-raiR-876-3p UAGUGGUUUACAAAGUAAUUCA cbr-miR-124 UAAGGCACGCGOUGAAUGCCA πunu-miR-876-5p UGGAUUUCUCUGUGAAUCACUA cbr-miR-228 AAUGGCACUGCAUGAAUUCACGG mmu-mιR-877 GUAGAGGAGAUGGCGCAGGG cbr-miR-230 GUAUUAGUUGUGCGACCAGGAAA mmu-miR-877* UGUCCUCUUCUCCCUCCUCCCA cbr-miR-231 UAAGCUCGUGAACAACAGGCAGGA mmu-miR-878-3p GCAUGACACCACACUGGGUAGA cbr-miR-232 UAAAUGCAUCUUAACUGCGGUGA mmu-miR-878-5p UAUCUAGUUGGAUGUCAAGACA cbr-miR-233 UUGAGCAAUGCGCAUGUGCGGGA mmu-miR-879 AGAGGCUUAUAGCUCUAAGCC cbr-imR-234 UUAUUGCUCGAGAAUACCCUU mmu-miR-879* GCUUAUGGCUUCAAGCUUUCGG obr-miR-235 UAUUGCACUUUCCCUGGCCAGA mmu-miR-880 UACUCCAUCCUCUCUGAGUAGA cbr-miR-236 UAAUACUGUCAGGUAAUGACGCU mmu-mlR-881 AACUGUGUCUUUUCUGAAUAGA cbr-miR-239a UUUGUACUACAAUUAGGUACUGG mmu-mjR-881* CAGAGAGAUAACAGUCACAUCU obr-miR-239b UUGUACUGCACAAAAGUACUG mmu-miR-882 AGGAGAGAGUUAGCGCAUUAGU cbr-miR-240 UACUGGCCUCCAAAUUUUCGCU mmu-miR-883a-3p UAACUGCAACAGCUCUCAGUAU cbr-miR-241 UGAGGUAGGUGUGAGAAAUGA mmu-miR-883a-Sp UGCUGAGAGAAGUAGCAGUUAC cbr-raiR-242 UUGCGUAGGCCUUUGUUUCGA mmu-miR-883b-3p UAACUGCAACAUCUCUCAGUAU cbr-miR-244 UCUUUGGUUGUACAAAGUGGUAUG mmu-miR-883b-5p UACUGAGAAUGGGUAGCAGUCA cbr-miR-245 AUUGGUCCCCUCCAAGUAGCUC mmu-miR-9 UCUUUGGUUAUCUAGCUGUAUGA cbr-miR-246 UUACAUGUAUUGGOUAGGAGCU mmu-miR-9* AUAAAGCUAGAUAACCGAAAGU cbr-miR-248 UACACGUGCUCGGAUAACGCUCA mmu-πuR-92a UAUUGCACUUGUCCCGGCCUG cbr-miR-249 UCACAGGAUUUUUGAGUGUUGC mmu-miR-92a* AGGUGGGGAUUGGUGGCAUUAC cbr-miR-250 UCACAGUCAACUGUUGGCACGG ramu-miR-92b UAUUGCACUCGUCCCGGCCUCC cbr-miR-251 UUAAGUAGUGGUGCCGCUCUUAUU mmu-miR-93 CAAAGUGCUGUUCGUGCAGGUAG cbr-miR-252 UAAGUAGUAGUGCCGCAGGUAAC mmu-miR-93* ACUGCUGAGCUAGCACUUCCCG obr-raiR-253 CACACCUCACUAACACUAACU mmu-miR-96 UUUGGCACUAGCACAUUUUUGCU cbr-miR-254 UGCAAAUCUUUUGCAACUGUAUA mmu-miR-98 UGAGGUAGUAAGUUGUAUUGUU cbr-miR-255 AAACUGAAGAGAUUUUUUACAG mrau-miR-99a AACCCGUAGAUCCGAUCUUGUG cbr-miR-259 AAAUCUCAUCCUAAUCUGGUU mmu-miR-99b CACCCGUAGAACCGACCUUGCG cbr-miR-268 GGCAAGAAUUAGAAGCAGUUUUGGU mmu-miR-99b* CAAGCUCGUGUCUGUGGGUCCG cbr-miR-34 AGGCAGUGUGGUUAGCUGGUUG mne-miR 101 UACAGU ACUGUGAUAACUG AAG cbr-raiR-35 UCACCGGGUGAAAACUUGCAAG mne-miR-103 AGCAGCAUUGUACAGGGCUAUGA cbr-miR-353 CAAGUAUCAUGUGUUGGUAUC mne-miR-105 UCAAAUGCUCAGACUCCUGU cbr miR-354 ACCUUGUUUGUUGCUGCUCCU mne-miR-106a AAAAGUGCUUACAGUGCAGGUAGC cbr-miR-355 UUUGUUUUAGCCUGAGCUAUG πme-miR-106b UAAAGUGCUGACAGUGCAGAU cbr-miR-356 AUGAGCAACGCGAACAAAUCC mne-miR-107 AGCAGCAUUGUACAGGGCUAUCA cbr-miR-357 AAAAUGCCAGUCAUUGACGGA mne-miR-lOb UACCCUGU AGAACCGAAUUUGU cbr-miR-358 CAAUUGGUAUCCUUAGUCGUGG mne-miR-125b UCCCUGAGACCCUAACUUGUGA cbr-miR-359 UCACUGGUUAUCCUCUGUCGAA mne-miR-127 UCGGAUCCGUCUGAGCUUGGCU cbr-miR-36 UCACCGGGUGAAAAUUCGCAAU mne-miR-130a CAGUGCAAUGUUAAAAGGGC cbr-miR-360 UGACCGUAAUCCCGUUCACAA mne-miR-133a UUGGUCCCCUUCAACCAGCUGU cbr-miR-38 UCACCGGGAGACAACCUGGUAU mne-miR-134 UGUGACUGGUUGACCAGAGGG cbr-miR-39 UCACCGGGUGAAAAACGGUUAG mne-miR-140 AGUGGUUCUACCCUAUGGUAG obr-miR-392 UAUCAUCGAUCAUGUGAGCUGU mne-miR-144 UACAGUAUAGAUGAUGUACUAG obr-miR-40 UCACCGGGUGUCAAUCAGCUAG mne-miR-145 GUCCAGUUUUCCCAGGAAUCCCUU cbr-miR-4I UCACCGGGUGAAAAACUCCCA mne-raiR-147 GUGUGUGGAAAUGCUUCUGC obr-miR-42 CACCGGGUUAACAUCUACAG mne-miR-153 UUGCAUAGUCACAAAAGUGA obr-miR-43 UAUCACAGUUUACUUGCUGUCGC mne-miR-154 UAGGUUAUCCGUGUUGCCUUCG obr-miR-44 UGACUAGAGACACAUUCAGCU mne-miR-15a UAGCAGCACAUAAUGGUUUGUG obr-miR-45 UGACUAGAGACACAUUCAGCU mne-miR-15b UAGCAGCACAUCAUGGUUUACA cbr-miR-46 UGUCAUGGAGUCGCUCUCUUCA mne-miR-16 UAGCAGCACGUAAAUAUUGGCG cbr-miR-47 UGUCAUGGAGGCGCUCUCUUCA mne-miR-17-3p ACUGCAGUGAAGGCACUUGU cbr-miR-48 UGAGGUAGGCUCAGUAGAUGCGA mne-miR-17-5p CAAAGUGCUUACAGUGCAGGUAGU cbr-miR-49 AAGCACCACGAGAAGCUGCAGA mne-miR-18 UAAGGUGCAUCUAGUGCAGAUA cbr-miR-50 UGAUAUGUCUGAUAUUCUUGGGUU mne-miR-181a AACAUUCAACGCUGUCGGUGAGU cbr-miR-51 UACCCGUAGCUCCUUGCCAUGUU mne-miR-181a* ACCAUCGACCGUUGAUUGUACC cbr-miR-52 CACCCGUACAUAUGUUUCCGUGCU mne-miR-181b AACAUUCAUUGCUGUCGGUGGGUU obr-miR-55 UACCCGUAUAUUUUUCUGCCGAG mne-miR-183 UAUGGCACUGGUAGAAUUCACUG cbr-miR-57 UACCCUGUAGAUCGAGCUGUGUGU mne-πuR-184 UGGACGGAGAACUGAUAAGGGU cbr-miR-58 UGAGAUCGUUCAGUACGGCAAU mne-miR-187 UCGUGUCUUGUGUUGCAGCCG cbr-miR-60 UAUUAUGCACAUUUUCUAGUCCA mne-miR-188 CAUCCCUUGCAUGGUGGAGGGU cbr-miR-61 UGACUAGAACCUUGACUCUGCUC mne-miR-189 GUGCCUACUGAGCUGAU AUCAGU cbr-miR-62 UGAUAUGUAAUCUAGCUUACAG mne-miR-194 UGUAACAGCAACUCCAUGUGGA cbr-miR-64 CAUGACACUGAAGCGUGUACGGA mne-miR-197 UUCACCACCUUCUCCACCCGGC cbr-miR-67 UCACAACCUCCUAGAAAGAGUAGA mne-miR-198 GGUCCAGAGGGGAAAUAGG cbr-miR-70 UAAUACGUGAUUGGUGUUCCCAG mne-miR-199a CCCAGUGUUCAGACUACCUGUUC cbr-miR-7l UGAAAGACAUGGGUAGUGA mnβ miR-19a UGUGCAAAUCUAUGCAAAACUGA cbr-miR-72 AGGCAGAUGUUGGCAUAGC iraie-miR-19b UGUGCAAAUCCAUGCAAAACUGA obr-miR-73 UGGCAAGAUGUUGGCAGUUCAGU iraie-miR-20 UAAAGUGCUUAUAGUGCAGGUA cbr-miR-74 UGGCAAGAAAUGGCAGUCUAGA mne-miR-204 UUCCCUUUGUCAUCCUAUGCCU cbr-miR-75 UUAAAGCUACCAACCGCCUUCA mne-miR-205 UCCUUCAUUCCACCGGAGUCUG obr-miR-77 UUCAUCAGGCCAUAGCUGUCCA mne-miR-206 UGGAAUGUAAGGAAGUGUGUGG cbr-miR-784 UGGCACAAUACCUGUAUGUAGA mne-miR-21 UAGCUUAUCAGACUGAUGUUGA cbr-miR-785 UAAGUGAAUACUCUGUGUUGA mne-miR-211 UUCCCUUUGUCAUCCUUCGCCU cbr-miR-786 UAAUGCCCUGUACGAGAUUUGGU mne-miR-214 ACAGCAGGCACAGACAGGCAG cbr-miR-787 UAAGCUCGUCUUAGUUUUCCUCU mne-miR-215 AUGACCUAUGAAUUGACAGAC cbr-miR-788 UCCGCUUCUCAAUGCUCCAUUUGCAA mne-miR-218 UUGUGCUUGAUCUAACC AUGU cbr-miR-789a UCCCUGCCUGGGUCAAAUGUUUU mne-miR-22 AAGCUGCCAGUUGAAGAACUGU cbr-miR-789b GCCCUGCCUGGGUCACCAUGUGA mne-miR-220 CCACCACCAUGUCUGACACUUU obr-miR-79 AUAAAGCUAGGUUACCAAAGCU mne-πuR-224 CAAGUCACUAGUGGUUCCGUUUA cbr-miR-790 CUUGGCACUCGCGAACACCGCG mne-miR-23a AUCACAUUGCCAGGGAUUUCC obr-miR-791 AUUGGCACUCCGCUGAUUUGGUG mne-miR-24 UGGCUCAGUUCAGCAGGAACAG obr-miR-792 UUGAAAUUUUUUCUAUUUUCGGU mne-miR-25 CAUUGCACUUGUCUCGGUCUGA cbr-miR-80 UGAGAUCAUUAGUUGAAAGCCGA mne-miR-26a UUCAAGUAAUCCAGGAUAGGCU cbr-miR-81 UGAGAUCAUCGUGAAAGCUAGU mne-miR-27a UUCACAGUGGCUAAGUUCCGCC cbr-miR-82 UGAGAUCAUCGUGAAAGCCAGU mne-miR-28 AAGGAGCUCACAGUCUAUUGAG cbr-miR-83 UAGCACCAUAUAAAUUCAGUGU πuie-πiiR-29a CUAGCACCAUCUGAAAUCGGUU cbr-miR-84 UGAGGUAGUUUGCAAUGCUGUC mne miR 29b UAGCACCAUUUGAAAUCAGU cbr miR-85 UACAAAGUAUUUGAAAAGGCGUGC mne miR 30b UGUAAACAUCCUACACUCAGC cbr-miR-86 UAAGUGAAUGCUUUGCCACAGUC mne-miR-300 UGUAAACAUCCUACACUCUCAGC cbr-imR-87 GUGAGCAAAGUUUCAGGUGU mne-miR-30d UGUAAACAUCCCCGACUGGAAG cbr-miR-90 UGAUAUGUUGUUUGAAUGCCCC mne-tniR-31 GGCAAGAUGCUGGCAUAGCUG eel let 7 UGAGGUAGUAGGUUGUAUAGUU mπe-miR-32 UAUUGCACAUUACUAAGUUGC cel-lin-4 UCCCUGAGACCUCAAGUGUGA mne-tniR-33 GUGCAUUGUAGUUGCAUUG oel-lsy-6 UUUUGUAUGAGACGCAUUUCG rane-miR 34a UGGCAGUGUCUUAGCUGGUUGU eel miR-1 UGGAAUGUAAAGAAGUAUGUA πuie-tniR-7 UGGAAGACUAGUGAUUUUGUU eel πuR-1018 AGAGAGAUCAUUGGACUUACAG mne-miR-9 UCUUUGGUUAUCUAGCUGUAUGA cel-πuR-1019 CUGUAAUUCCACAUUGCUUUCCAG mne-miR-92 UAUUGCACUUOUCCCGGCCUGU od-miR-1019* GUGAGCAUUGUUCGAGUUUCAUUUU imie-miR-93 AAAGUGCUGUUCGUGCAGGUAG oel miR 1020 AUUAUUCUGUGACACUUUCAG mne-miR-96 UUUGGCACUAGCACAUUUUUGC oel-miR-1021 AAGUGAGAUCAUGUGAAAUCCUCGG mne-miR-99a AACCCGUAGAUCCGAUCUUGUG cel-miR-1022 AAGAUCAUUGUUAGGACGCCAUC oar-miR-127 AUCGGAUCCGUCUGAGCUUGGCU cεl-miR-124 UAAGGCACGCGGUGAAUGCCA oar miR-136 ACUCCAUUUGUUUUGAUGAUGGA cd-miR-1817 UAGCCAAUGUCUUCUCUAUCAUG oar-miR-431 UGUCUUGCAGGCCGUC AUGC AGG cel miR-1818 UGUGGUCUUCAUGCCAUGAUUUU oar-miR-432 UCUUGGAGUAGGUCAUUGGGUGG cel-miR-1819 UGGAAUGAUUGAGCUUGAUGGA odi-let-7a UGAGGUAGUGGACUGUUUAGGA cel-miR-1820 UUUUGAUUGUUUUUCGAUGAUGUUC odi-let-7b UGAGGUAGUGGUUGUAAUAGCU cel raiR 1821 UGAGGUCUUAUAGUUAGGUAG odi-let-7c AUGAGGUAGUAGGUUAUGCUGU cel-miR 1822 GAGCUGCCCUCAGAAAAACUCU odi-let-7d UGAGGUAGUGGGUUGUAUCGCU cel-miR 1823 UACUGGAAGUGUUUAGGAGUAA odi miR 124a UAAGGCACGCGGUGAAUGCUAA cel miR 1824 UGGCAGUGUUUCUCCCCCAACUU odi-miR-124b UAAGGCACUCGGUGAAUGCUAA oel miR 1828 ACUGGAAGCAUUUAAGUGAUAGU odi-miR-1468 UAAGGCGAGAUGAGGUCUUUGGACA oel miR 1829a CAACCAUUGGAAUUUCUCUAUU odi-miR-1469 UGGCAAGAUGGUCGCGAAACUUCC eel miR-1829b AAGCGAUCUUCUAGAUGGUUGUA odi-miR-1470 CACACCUUAACACCAGUGCGCUGA cel-miR-1829c AAGCGAAAUUCAAGAUGGUUGUA odi-miR-1471 UCACCUUGGUAUCAAAAUUUGCG eel miR 1830 CGAGGUUUCACGUUUUCUAGGC odi-miR 1472 UGGCAGUAAGAUGAUUUAGUACC oel-miR-1831 ACCUGGCUGGGGGUAUCUCGUG odi-miR 1473 UCAAGCUCGGGUUUAUCGGUGU cel-miR-1832 UGGGCGGAGCGAAUCGAUGAU odi miR 1474 UGUCAGGACUGAGGUUGUGCUU cel-miR-1833 CGAGGCUUGCGAAAUAAGUGUGC odi miR 1475 UCUGGGCACAGGUAAACUUUG cel-miR-1834 AGAGAUCAACCAUUGAGAUCCAA odi miR-1476-3p UACAUGUACCGUUGCUCAGAGA cel-miR-2 UAUCACAGCCAGCUUUGAUGUGC odi miR-1476-5p UCUGGGCAAAGGUAAAUGUAUG cel-πuR-227 AGCUUUCGACAUGAUUCUGAAC odi-miR-1477 UGUGCAAAGCCCUAACAUUUCUA cel-miR-228 AAUGGCACUGCAUGAAUUCACGG odi-miR-1478 UGGAACUAGUAUGGAGCAGGCUGA cel-miR 229 AAUGACACUGGUUAUCUUUUCCAUCG odi-miR-1479 CAACGAGUCCUUGAAAUUACCGG eel miR-230 GUAUUAGUUGUGCGACCAGGAGA odi-miR-1480 GGUGGCUCAUUCUCGGCUUGUGUC cel-miR 231 UAAGCUCGUGAUCAACAGGCAGAA odi miR 1481 CCACAAUGAAGAUAGAAGAUGGCU cel-miR-232 UAAAUGCAUCUUAACUGCGGUGA odi-miR-1482 UUGAACUUCUCAGGAACAGGCUAG cel-miR-233 UUGAGCAAUGCGCAUGUGCGG odi-miR-1483-3p AGGGCCAUCGCCUAUAUCUGCCCA cel-miR-234 UUAUUGCUCGAGAAUACCCUU odi-miR-1483-5p CGGCAGUGAGUCGAUAGCGCCCUUU cel-miR-235 UAUUGCACUCUCCCCGGCCUGA odi-miR-1484 UGAAACUUCGUAGAUUUGGUCACU oel-miR-236 UAAUACUGUCAGGUAAUGACGCU odi-miR-1485 AAGGUAAAGCUGGCUACAUAACGU oel miR 237 UCCCUGAGAAUUCUCGAACAGCU odi-miR-1486 CUAGGUGGUUUUUUCGAUGAAGGU oel πuR-238 UUUGUACUCCGAUGCCAUUCAGA odi-miR-1487 UGGCAGUGGGGACAAGUUUAGG eel miR-239a UUUGUACUACACAUAGGUACUGG odi miR-1489 UAGGUAAACCACGGAUUGCUUA cel-miR-239b UUUGUACUACACAAAAGUACUG odi-miR-1490a AGGCAGUGAGUUGAUAGCGCCCUGA eel miR-240 UACUGGCCCCCAAAUCUUCGCU odi-miR- 1490b AGGCAGUGAGUUGAUAGCGCCCUGU oel-miR-241 UGAGGUAGGUGCGAGAAAUGA odi-miR-1491 ACCCUGAGUGCAGAAUCUUGGU oel miR-242 UUGCGUAGGCCUUUGCUUCGA odl-πuR-1492 UAUUGCACAUACCCGGCCUUG cel-miR-243 CGGUACGAUCGCGGCGGGAUAUC odι-πuR-1493 AGAACUGUCUGAAUGGUUGGC oel miR 244 UCUUUGGUUGUACAAAGUGGUAUG odi-πuR-1494 AAGCAGCAAGGACAGUGUUUGG cel-miR-245 AUUGGUCCCCUCCAAGUAGCUC odi miR 1495 AGUGUAAUACCCAUGGAAGCAUU cel-miR-246 UUACAUGUUUCGGGUAGGAGC odi-miR-1496 UAGCAGUGAGAGUUUAGCAUUCGCAAC cel-miR-247 UGACUAGAGCCUAUUCUCUUCU odi-miR-1497a UUGAAGAACUGCAGGUGGUGGAU cel-miR-248 AUACACGUGCACGGAUAACGCUCA odi-miR-1497b UUGAAGAACUGCAGGUGGUGGUC cel-miR-249 UCACAGGACUUUUGAGCGUUGCC odi-miR-1497c UUGAAGAAUUGCAGGUGGUGGUC cel-miR 250 AAUCACAGUCAACUGUUGGCA odi miR-1497d UUGAAGAAUUGCAGGUGGUGGAU cel-miR 251 UUAAGUAGUGGUGCCGCUCUUAUU odi-miR-1497c UUGAAGAAUUACAGGUGGUGGAA oel miR 252 AUAAGUAGUAGUGCCGCAGGUAA odi-miR-1497t UUGAAGAAUUGCAGGUGGUAGGG oel-miR-253 UUAGUAGGCGUUGUGGGAAGG odi-miR-1497g UUGAAGAAUUGCAGGUGGUAGGU oel miR 253* CACACCUCACUAACACUGACC odi miR 1497h UUGAAGAAUUGCAGGUGGUGGAC oel miR-254 UGCAAAUCUUUCGCGACUGUAGG odi-miR-1498 AGGAAUGUAGAAUUAGGAAUUCGG cel-miR-255 AAACUGAAGAGAUUUUUUACAG odi-miR-1499 CACACCUUUACCAGUGCGCUGG cel-miR-256 UGGAAUGCAUAGAAGACUGUA odi miR- 1500 UUGAUAAGACUGUCAUUGAUGA cel-miR-257 GAGUAUCAGGAGUACCCAGUGA odi-miR- 1501 UAUGCUGUACUGCAAAGGCUCC cel-miR-258 GGUUUUGAGAGGAAUCCUUUU odi-miR-1502 UGAACUUUACCAUGGAACCGGG cel-miR 259 AAAUCUCAUCCUAAUCUGGUAGCA odi miR 1503 CGAGGAAGAUCUUGUGGCAA oel-πuR-260 GUGAUGUCGAACUCUUGUAG odi miR 1504 AGUGUACUUGGUGCUUGGGUU cel-miR-261 UAGCUUUUUAGUUUUCACG odi miR 1505 AGUAGACUGACUCGGCGCCUCAU cel-miR-262 GUUUCUCGAUGUUUUCUGAU odi-miR-1506 UGGCAGUACCUAAGUCCCUGA cel-miR-264 GGCGGGUGGUUGUUGUUAUG odi-miR-la UGGAAUGUUGAGAAGUGUGAUU cel-imR-265 UGAGGGAGGAAGGGUGGUAU odi-miR-lb UGGAAUGUUAAGAAGUGUGACU cel-nuR-266 AGGCAAGACUUUGGCAAAGC odi-miR-lc UGGAAUGUAAAGAAGUAUGUGA cel-miR-267 CCCGUGAAGUGUCUGCUGCA odi-miR-219 UGAUUGUCCAAACGCAAUUAG eel miR-268 GGCAAGAAUUAGAAGCAGUUUGGU odι-miR-281 UGUCAUGGAAUUGCUCUCUUG cel-miR-269 GGCAAGACUCUGGCAAAACU odi-miR 31 AGGCAAGAUGCUGGCAUUGCUG cel-miR-270 GGCAUGAUGUAGCAGUGGAG odi-miR-7 UGGAAGACUAGUGAUUUUGUUG cel-miR-271 UCGCCGGGUGGGAAAGCAUU odi-miR-92a UAUUGCACUCGUCCCGGCCUUG cel-πuR-272 UGUAGGCAUGGGUGUUUG odi-miR-92b UAUUGCACUGGUCCCGACUAAU cel-πuR-273 UGCCCGUACUGUGUCGGCUG pbi miR-506 UAAGGCACCCUUCUGAGUAGA oel-miR-34 AGGCAGUGUGGUUAGCUGGUUG pbi-miR-507 UUUUGCACCUUUUGGAGUGAA cel-miR-35 UCACCGGGUGGAAACUAGCAGU pbi-πuR-508 UGAUUGUCACCUUUUUGAGUAGA cel-miR-353 CAAUUGCCAUGUGUUGGUAUU pbi-miR-509 UGAUUGAUACGUCUGUGGGUAGA cel-miR-354 ACCUUGUUUGUUGCUGCUCCU pbi πuR-510 UACUCCGGAGAGUGGCAAUCACA cel-miR-355 UUUGUUUUAGCCUGAGCUAUG pbi-πuR-513a UUCACAGGGAGGUGUCAUUUAU cel-πuR-356 UUGAGCAACGCGAACAAAUCA pbi-miR-513b UUCACAAGGAGGUGUCAUUUAU cel-miR-357 UAAAUGCCAGUCGUUGCAGGAGU pbi-imR-513c UUCACAGGGAGGUGUCAUUUGU cel-miR-358 AUUGGUAUCCCUGUCAAGGUC pbi-miR-514 AUUGACACUUCUGUGAGUAG cel-miR-359 UCACUGGUCUUUCUCUGACGAA ppa-miR-1 UGGAAUGUAAAGAAGUAUGUA cel-miR-36 UCACCGGGUGAAAAUUCGCAUG ppa-miR-100 AACCCGUAGAUCCGAACUUGUG cel-raiR-360 UGACCGUAAUCCCGUUCACAA ppa-miR-101 UACAGUACUGUGAUAACUGAAG cel-miR-37 UCACCGGGUGAACACUUGCAGU ppa-miR-103 AGCAGCAUUGUACAGGGCUAUGA cel-miR-38 UCACCGGGAGAAAAACUGGAGU ppa-miR-105 UCAAAUGCUCAGACUCCUGU cel-miR-39 UCACCGGGUGUAAAUCAGCUUG ppa-miR-106a AAAAGUGCUUACAGUGCAGGUAGC cd-miR-392 UAUCAUCGAUCACGUGUGAUGA ppa-miR-106b UAAAGUGCUGACAGUGCAGAU oel-miR-40 UCACCGGGUGUACAUCAGCUAA ppa-raiR-107 AGCAGCAUUGUACAGGGCUAUCA cel-miR-41 UCACCGGGUGAAAAAUCACCUA ppa-miR-10a UACCCUGUAGAUCCGAAUUUGUG cel-miR-42 UCACCGGGUUAACAUCUACAGA ppa-miR-lOb UACCCUGUAGAACCGAAUUUGU cel-miR-43 UAUCACAGUUUACUUGCUGUCGC ppa miR-124a UUAAGGCACGCGGUGAAUGCCA cel-miR-44 UGACUAGAGACACAUUCAGCU ppa-miR-125b UCCCUGAGACCCUAACUUGUGA eel miR-45 UGACUAGAGACACAUUCAGCU ppa-miR-128 UCACAGUGAACCGGUCUCUUUU oel-miR-46 UGUCAUGGAGUCGCUCUCUUCA ppa-tniR-130a CAGUGCAAUGUUAAAAGGGC cel-miR-47 UGUCAUGGAGGCGCUCUCUUCA ppa-miR-133a UUGGUCCCCUUCAACCAGCUGU cel-miR-48 UGAGGUAGGCUCAGUAGAUGCGA ppa-imR-134 UGUGACUGGUUGACCAGAGGG cel-imR-49 AAGCACCACGAGAAGCUGCAGA ppa-miR-135 UAUGGCUUUUUAUUCCUAUGUGA cel-miR-50 UGAUAUGUCUGGUAUUCUUGGG ppa-miR 136 ACUCCAUUUGUUUUGAUGAUOGA cel-miR-51 UACCCGUAGCUCCUAUCCAUGUU ppa-nuR-139 UCUACAGUGCACGUGUCU cel-miR-52 CACCCGUACAUAUGUUUCCGUGCU ppa miR 141 AACACUGUCUGGUAAAGAUGC oel-miR-53 CACCCGUACAUUUGUUUCCGUGCU ppa πuR-143 UGAGAUGAAGCACUGUAGCUCA cel-miR-54 UACCCGUAAUCUUCAUAAUCCGAG ppa-miR-144 UACAGUAUAGAUGAUGUACUAC cel-miR-55 UACCCGUAUAAGUUUCUGCUGAG ppa-πuR-147 GUGUGUGGAAAUGCUUCUGC cel-miR-56 UACCCGUAAUGUUUCCGCUGAG ppa-mιR-154 UAGGUUAUCCGUGUUGCCUUCG cel-miR-56* UGGCGGAUCCAUUUUGGGUUGUA ppa-πuR-15a UAGCAGCACAUAAUGGUUUGUG cel-miR-57 UACCCUGUAGAUCGAGCUGUGUGU ppa-πuR-15b UAGCAGCACAUCAUGGUUUACA cel-miR-59 UCGAAUCGUUUAUCAGGAUGAUG ppa-miR-16 UAGCAGCACGUAAAUAUUGGCG cel-miR-60 UAUUAUGCACAUUUUCUAGUUCA ppa-miR-17-3p ACUGCAGUGAAGGCACUUGU cel-miR-61 UGACUAGAACCGUUACUCAUC ppa-miR-17-5p CAAAGUGCUUACAGUGCAGGUAGU ceI-miR-62 UGAUAUGUAAUCUAGCUUACAG ppa-miR-18 UAAGGUGCAUCUAGUGCAGAUA cel-miR-63 UAUGACACUGAAGCGAGUUGGAAA ppa-miR- 181a AACAUUCAACGCUGUCGGUGAGU cel-miR-64 UAUGACACUGAAGCGUUACCGAA ppa-miR-181a* ACCAUCGACCGUUGAUUGUACC eel miR-65 UAUGACACUGAAGCGUAACCGAA ppa-miR-181b AACAUUCAUUGCUGUCGGUGGGUU cel-πuR-66 CAUGACACUGAUUAGGGAUGUGA ppa-miR 181o AACAUUCAACCUGUCGGUGAGU cel-miR-67 UCACAACCUCCUAGAAAGAGUAGA ppa-πuR-183 UAUGGCACUGGUAGAAUUCACUG cel-miR-70 UAAUACGUCGUUGGUGUUUCCAU ppa-miR-186 CAAAGAAUUCUCCUUUUGGGCUU cel-miR-71 UGAAAGACAUGGGUAGUGA ppa-miR-187 UCGUGUCUUGUGUUGCAGCCG cel-miR-72 AGGCAAGAUGUUGGCAUAGCUGA ppa-miR-188 CAUCCCUUGCAUGGUGGAGGGU cel-πuR-73 UGGCAAGAUGUAGGCAGUUCAGU ppa-miR-189 GUGCCUACUGAGCUGAUAUCAGU eel miR 74 UGGCAAGAAAUGGCAGUCUACA ppa-miR-190 UGAUAUGUUUGAUAUAUUAGGU oel-miR-75 UUAAAGCUACCAACCGGCUUCA ppa-miR-195 UAGCAGCACAGAAAUAUUGGC cel-πnR-76 UUCGUUGUUGAUGAAGCCUUGA ppa miR-196 UAGGUAGUUUCAUGUUGUUGGG oel-miR-77 UUCAUCAGGCCAUAGCUGUCCA ppa-miR-197 UUCACC ACCUUCUCC ACCCAGC cel-miR-78 UGGAGGCCUGGUUGUUUGUGC ppa-πuR-198 GGUCCAGAGGGGAGAUAGG cel-miR-784 UGGCACAAUCUGCGUACGUAGA ppa-miR-199a CCCAGUGUUCAGACUACCUGUUC cel-miR-785 UAAGUGAAUUGUUUUGUGUAGA ppa-miR-19a UGUGCAAAUCUAUGCAAAACUGA cel-miR-786 UAAUGCCCUGAAUGAUGUUCAAU ppa-miR-19b UGUGCAAAUCCAUGCAAAACUGA csl miR 787 UAAGCUCGUUUUAGUAUCUUUCG ppa-miR-20 UAAAGUGCUUAUAGUGCAGGUA del-miR-788 UCCGCUUCUAACUUCCAUUUGCAG ppa-miR-204 UUCCCUUUGUCAUCCUAUGCCU eel πuR-789 UCCCUGCCUGGGUCACCAAUUGU ppa-miR-205 UCCUUCAUUCCACCGGAGUCUG eel imR-79 AUAAAGCUAGGUUACCAAAGCU ppa-miR-21 UAGCUUAUCAGACUGAUGUUGA cel-miR-790 CUUGGCACUCGCGAACACCGCG ppa-miR-214 ACAGCAGGCACAGACAGGCAG oel-miR-791 UUUGGCACUCCGCAGAUAAGGCA ppa-miR-216 U AAUCUC AGCUGGC AACUGUG oel-miR-792 UUGAAAUCUCUUCAACUUUCAGA ppa-miR-217 UACUGCAUCAGGAACUGAUUGGAU cel-miR-793 UGAGGUAUCUUAGUUAGACAGA ppa-miR-218 UUGUGCUUGAUCU AACCAUGU oel-miR 794 UGAGGUAAUCAUCGUUGUCACU ppa-miR-22 AAGCUGCCAGUUGAAGAACUGU oel-miR-795 UGAGGUAGAUUGAUCAGCGAGCUU ppa-miR-220 CCACACCGUAUCUGACACUUU cel-miR-796 UGGAAUGUAGUUGAGGUUAGUAA ppa-miR 221 AGCUACAUUGUCUGCUGGGUUUC cel-miR-797 UAUCACAGCAAUCACAAUGAGAAGA ppa-miR 223 UGUCAGUUUGUCAAAUACCCC cel-miR-798 UAAGCCUUACAUAUUGACUGA ppa-miR-224 CAAGUCACUAGUGGUUCCGUUUA cel-miR-799 UGAACCCUGAUAAAGCUAGUGG ppa-miR-23a AUCACAUUOCCAGGGAUUUCC oel-miR-80 UGAGAUCAUUAGUUGAAAGCCGA ppa-miR-23b AUCACAUUGCCAGGGAUUACCAC cel-miR-800 CAAACUCGGAAAUUGUCUGCCG ppa-miR-24 UGGCUCAGUUCAGCAGGAACAG oel-miR-81 UGAGAUCAUCGUGAAAGCUAGU ppa-miR-25 CAUUGCACUUGUCUCGGUCUGA cεl-miR-82 UGAGAUCAUCGUGAAAGCCAGU ppa-miR-26a UUCAAGUAAUCCAGGAUAGGCU cel-miR-83 UAGCACCAUAUAAAUUCAGUAA ppa-niiR-27a UUCACAGUGGCUAAGUUCCGCC eel πuR-84 UGAGGUAGUAUGUAAUAUUGUA ppa-miR-28 AAGGAGCUCACAGUCUAUUGAG cel-miR-8S UACAAAGUAUUUGAAAAGUCGUGC ppa-miR-29a CUAGCACCAUCUGAAAUCGGUU cel-miR-86 UAAGUGAAUGCUUUGCCACAGUC ppa-miR-29b UAGCACCAUUUGAAAUCAGU cel-miR-87 GUGAGCAAAGUUUCAGGUGUGC ppa-miR-30a-3p CUUUCAGUCGGAUGUUUGCAGC cel-miR-90 UGAUAUGUUGUUUGAAUGCCCCU ppa-miR-30a-5p UGUAAACAUCCUCGACUGGAAG cfa-Iβt-7a UGAGGUAGUAGGUUGUAUAGUU ppa-miR-30b UGUAAACAUCCUACACUCAGC cfa-let-7o UGAGGUAGUAGGUUGUAUGGUU ppa-miR-30d UGUAAACAUCCCCGACUGGAAG ofa let-7e UGAGGUAGGAGGUUGUAUAGUU ppa-miR-31 CGCAAGAUGCUGGCAUAGCUG ofa-let-7f UGAGGUAGUAGAUUGUAUAGUU ppa-miR-32 UAUUGCACAUUACUAAGUUGC cfa-let-7g UGAGGUAGUAGUUUGUACAGUU ppa-miR-33 GUGCAUUGUAGUUGCAUUG cfa-let-7j UGAGGUAGUAGAGUGCAGUAGUU ppa-miR-34a UGGCAGUGUCUUAGCUGGUUGU cfa-miR-1 UGGAAUGUAAAGAAGUAUGUA ppa-miR-7 UGGAAGACUAGUGAUUUUGUU cfa-miR-10 UACCCUGUAGAUCCGAAUUUGU ppa-miR-92 UAUUGCACUUGUCCCGGCCUGU cfa-miR-101 UACAGUACUGUGAUAACUGA ppa-miR-93 AAAGUGCUGUUCGUGCAGGUAG ofa-miR-103 AGCAGCAUUGUACAGGGCUAUGA ppa-miR-95 UUCAACGGGUAUUUAUUGAGCA cfa-miR-106a AAAGUGCUUACAGUGCAGGUAG ppa-miR-96 UUUGGCACUAGCACAUUUUUGC efa-miR-lOβb UAAAGUGCUGACAGUGCAGAU ppa-miR-98 UGAGGUAGUAAGUUGUAUUGUU cfa-miR-107 AGCAGCAUUGUACAGGGCUAU ppa-miR-99a AACCCGUAGAUCCGAUCUUGUG cfa-miR-122 UGGAGUGUGACAAUGGUGUUUG ppy-miR-100 AACCCGUAGAUCCGAACUUGUG cfa-miR-12₄ UAAGGCACGCGGUGAAUGCCA ppy-miR-101 UACAGUACUGUGAUAACUGAAG cfa-miR-125a UCCCUGAGACCCUUUAACCUGU ppy-miR- 103 AGCAGCAUUGUACAGGGCUAUGA cfa-miR-125b UCCCUGAGACCCUAACUUGUGA ppy-miR-105 UCAAAUGCUCAGACUCCUGU cfa-miR-126 CAUUAUUACUUUUGGUACGCG ppy-miR- 106a AAAAGUGCUUACAGUGCAGGUAGC cfa-miR-127 UCGGAUCCGUCUGAGCUUGGCU ppy-miR-106b UAAAGUGCUGACAGUGCAGAU cfa-miR-1271 CUUGGCACCUAGUAAGCACU ppy-miR-107 AGCAGCAUUGUACAGGGCUAUCA cfa-miR-128 UCACAGUGAACCGGUCUCUUU ppy-miR-lOa UACCCCGUAGAUCCGAAUUUGUG cfa-πuR-129 CUUUUUGCGGUCUGGGCUUGC ppy-miR- 124a UUAAGGCACGCGGUGAAUGCCA cfa-miR-1306 CCACCUCCCCUGCAAACGUCC ppy-miR-125b UCCCUGAGACCCUAACUUGUGA cfa-miR-1307 ACUCGGCGUGGCGUCGGUCGUG ppy-miR-127 UCGGAUCCGUCUGAGCUUGGCU cfa-πuR-130a CAGUGCAAUGUUAAAAGGGCAU ppy-miR-128 UCACAGUGAACCGGUCUCUUUU cfa-miR-130b CAGUGCAAUGAUGAAAGGGCAU ppy-miR-133a UUGUCCCCUUCAACCAGCUGU ofa-miR-132 UAACAGUCUACAGCCAUGGUCGC ppy-miR-134 UGUGACUGGUUGACCAGAGGG cfa-miR-135 UGUAGGGAUGGAAGCCAUGAAA ppy-nuR-135 UAUGGCUUUUUAUUCCUAUGUGA cfa-miR-136 ACUCCAUUUGUUUUGAUGAUGGA ppy-miR-136 ACUCCAUUUGUUUUGAUGAUGGA cfa-miR-137 UUAUUGCUUAAGAAUACGCGU ppy-miR-141 AACACUGUCUGGUAAAGAUGG cfa-miR-138a AGCUGGUGUUGUGAAUCAGGCCG ppy-miR-143 UGAGAUGAAGCACUGUAGCUCA cfa-miR-138b AGCUGGUGUUGUGAAUCAUGCCGA ppy-miR-144 UACAGUAUAGAUGAUGUACUAG cfa-miR-139 UGGAGACGCGGCCCUGUUGGAA ppy-miR-145 GUCCAGUUUUCCCAGGAAUCCCUU ofa-miR-140 ACCACAGGGUAGAACCACGGA ppy-miR-147 GUGUGUGGAAAUGCUUCUGC ofa-miR-142 CCCAUAAAGUAGAAAGCACUA ppy-raiR-153 UUGCAUAGUCACAAAAGUGA cfa-miR-143 UGAGAUGAAGCACUGUAGCUC ppy-miR-154 UAGGUUAUCCGUGUUGCCUUCG cfa-miR-144 UACAGUAUAGAUGAUGUACUAG ppy-miR-15a UAGCAGCACAUAAUGGUUUGUG cfa-miR-146a UGAGAACUGAAUUCCAUGGGUU ppy-miR-15b UAGCAGCACAUCAUGGUUUACA cfa-miR-146b UGAGAACUGAAUUCCAUAGGCU ppy-miR-16 UAGCAGCACGUAAAUAUUGGCG cfa-miR-148a UCAGUGCACUACAGAACUUUGU ppy-miR-17-3p ACUGCAGUGAAGGCACUUGU cfa-miR-148b UCAGUGCAUCACAGAACUUUGU ppy-miR-17-5p CAAAGUGCUUACAGUGCAGGUAGU ofa-miR-150 UCUCCCAACCCUUGUACCAGUG ppy-miR-18 UAAGGUGCAUCUAGUGCAGAUA cfe-miR-151 UCGAGGAGCUCACAGUCUAGU ppy-miR-181a AACAUUCAACGCUGUCGGUGAGU cfa-miR-152 UCAGUGCAUGACAGAACUUGG ppy-miR-18 Ia* ACCAUCGACCGUUGAUUGUACC cfa-miR-155 UUAAUGCUAAUCGUGAUAGGGGU ppy-miR-181b AACAUUCAUUGCUGUCGGUGGGUU cfa-miR-15a UAGCAGCACAUAAUGGUUUGU ppy-miR- 182 UUUGGCAAUGGUAGAACUCACA cfa-miR-15b UAGCAGCACAUCAUGGUUUA ppy-miR-184 UGGACGGAGAACUGAUAAGGGU cfa-miR-16 UAGCAGCACGUAAAUAUUGGCG ppy-miR-187 UCGUGUCUUGUGUUGCAGCCG cfa-miR-17 ACUGCAGUGAAGGCACUUGUAG ppy-miR-188 CAUCCCUUGCAUGGUGGAGGGU cfa-miR-181a AACAUUCAACGCUGUCGGUGAG ppy-miR-189 GUGCCUACUGAGCUGAUAUCAGU ofa-miR-181b AACAUUCAUUGCUGUCGGUG ppy-miR-194 UGUAACAGCAACUCCAUGUGGA ofa-miR-181c AACAUUCAACCUGUCGGUGAGUU ppy-miR- 196 UAGGUAGUUUCAUGUUGUUGG cfa-miR-181d AACAUUCAUUGUUGUCGGUGGGU ppy-miR-196-2 UAGGUAGUUUCAUGUUGUUGGG cfe-miR-183 UAUGGCACUGGUAGAAUUCACU ppy-miR-197 UUCACCACCUUCUCCACCCAGC cfa-miR-1835 UGCACCCUGAGAGCUGGAGCAG ppy-miR-198 GGUCCAGAGGGGAGAUAGG ofa-miR-1836 UAGGCCAUGGUAGAUAGAGAUGG ppy-miR-199a CCCAGUGUUCAGACUACCUGUUC ofa-miR-1837 UCUCAGAGGGACUGCGACAUCU ppy-miR-19a UGUGCAAAUCUAUGCAAAACUGA ofa-miR-1838 CCACCAGCUGGCGUUCCCUGG ppy-miR-19b UGUGCAAAUCCAUGCAAAACUGA cfa-miR-1839 AAGGUAGAUAGAACAGGUCUUG ppy-miR-20 UAAAGUGCUUAUAGUGCAGGUA cfa-miR-1840 UCACGUGACGGGCCUCGGCG ppy-miR-200c AAUACUGCCGGGUAAUGAUGGA cfa-miR-1841 AGAGGAAAGCUGGACGGCAAGC ppy-miR-204 UUCCCUUUGUCAUCCUAUGCCU cfa-miR-1842 UGGCUCUGCGAGGUCAGCUCA ppy-miR-206 UGGAAUGUAAGGAAGUGUGUGG cfa-miR-1843 ACUGGAGGUCUCUGUCUGGCUU ppy-miR-21 UAGCUU AUC AGACUGAUGUUGA cfa-miR-1844 AGGACUACGGACGGGCUGAG ppy-miR-211 UUCCCUUUGUC AUCCUUCGCCU cfa-miR-185 UGGAGAGAAAGGCAGUUCCUGA ppy-miR-214 ACAGCAGGCACAGACAGGCAG ofa-miR-186 CAAAGAAUUCUCCUUUUGGGCU ppy-miR-215 AUGACCUAUGAAUUGACAGAC cfa-miR-191 CAACGGAAUCCCAAAAGCAGCU ppy-miR-216 UAAUCUCAGCUGGC AACUGUG ofa-miR-192 CUGACCUAUGAAUUGACAGCC ppy-miR-218 UUGUGCUUGAUCUAACCAUGU cfa-miR-193a UGGGUCUUUGCGGGCGAGAUGA ppy-miR-219 UGAUUGUCCAAACGCAAUUCU ofa-miR-193b CGGGGUUUUGAGGGCGAGAUGA ppy-miR-22 AAGCUGCCAGUUGAAGAACUGU cfa miR-194 UGUAACAGCAACLCCAUGUGGA ppy-miR 221 AGCUACAUUGUCUGCUGGGUUUC cfe miR-195 UAGCAGCACAGAAAUAUUGGCA ppy-miR-223 UGUCAGUUUGUCAAAUACCCC cfa-miR-196a UAGGUAGUUUCAUGUUGUUGGG ppy-miR-224 CAAGUCACUAGUGGUUCCGUUUA cfa miR-196b UAGGUAGUUUCCUGUUGUUGGGA ppy-miR-23a AUCACAUUGCCAGGGAUUUCC cfe-miR-197 UUCACCACCUUCUCCACCCAGC ppy-miR-23b AUCACAUUGCCAGGGAUUACCAC cfa-miR-199 ACAGUAGUCUGCACAUUGGUU ppy-miR-24 UGGCUCAGUUCAGCAGGAACAG cfe-πuR-l9a UGUGCAAAUCUAUGCAAAACUGA ppy-miR-25 CAUUGCACUUGUCUCGGUCUGA oft miR 19b UGUGCAAAUCCAUGCAAAACUG ppy miR 26a UUCAAGUAAUCCAGGAUAGGCU cfa-miR-20 UAAAGUGCUUAUAGUGCAGGUAG ppy-miR-27a UUCACAGUGGCUAAGUUCCGCC cfa-miR-200c UAAUACUGCCGGGUAAUGAUGaA ppy-miR-28 AAGGAGCUCACAGUCUAUUOAG cfa-miR-204 UUCCCUUUGUCAUCCUAUGCCU ppy-πuR-29a CUAGCACCAUCUGAAAUCQαUU cfa-miR-206 UGGAAUGUAAGGAAGUGUGUGG ppy-raiR-29b UAGCACCAUUUGAAAUCAGU cfa-miR-21 UAGCUUAUCAGACUGAUGUUGA ppy-miR-30a-3p CUUUCAGUCGGAUGUUUGCAGC cfa-miR-212 ACCUUGGCUCUAGACUGCUUACU ppy-miR-30a-5p UGUAAACAUCCUCGACUGGAAG cfa miR 216 AAAUCUCUGCAGGCAAAUGUGA ppy miR 31 GGCAAGAUGCUGGCAU AGCUG cfa-miR-218 UUGUaCUUGAUCUAACCAUGU ppy-miR-32 UAUUGCACAUUACUAAGUUGC cfa miR-219 UGAUUGUCCAAACGCAAUUCU ppy miR 33 GUGCAUUGUAGUUGCAUUG cfa-miR-219* AGAAUUGUGGCUGGACAUCUGU ppy-miR-34a UGGCAGUGUCUUAGCUGQUUGU cfa-imR-22 AAGCUaCCAGUUGAAGAACUGU ppy-miR-7 UGGAAGACUAGUGAUUUUOUU cfa-miR-221 AGCUACAUUGUCUGCUGGGUUU ppy-miR-92 UAUUGCACUUOUCCCαQCCUGU cfa-miR-224 CAAGUCACUAGUaOUUCCGUUU ppy-miR-93 AAAGUGCUGUUCGUGCAGGUAG cfa-iruR-23a AUCACAUUGCCAGGGAUUU ppy-miR-95 UUCAACGGGUAUUUAUUGAGCA cfa miR-23b AUCACAUUGCCAGGGAUUA ppy-miR-98 UGAGGUAGUAAGUUGUAUUGUU cfa-miR-24 UGGCUCAGUUCAGCAGGAACAGG ppy-miR-99a AACCCGUAGAUCCGAUCUUGUG cfa-miR-25 CAUUGCACUUGUCUCGGUCUGA ptr-miR-IOO AACCCGUAGAUCCGAACUUGUG cfa-miR-26a UUCAAGUAAUCCAGGAUAGGCU ptr miR-101 UACAGUACUGUGAUAACUGAAG cfa-miR-26b UUCAAGUAAUUCAGGAUAGGUU ptr-miR-103 AGCAGCAUUGUAC AGGGCUAUGA cfe-rmR-27a UUCACAGUGGCUAAGUUCCG ptr miR-105 UCAAAUGCUCAGACUCCUQU cfe-rmR-27b UUCACAGUGGCUAAGUUCUGC ptr miR 106a AAAAGUGCUUACAGUGCAGGUAGC cfe-miR-28 CACUAGAUUGUGAGCUCCUGGA ptr miR 106b UAAAGUGCUGACAGUGCAGAU ofe miR 29a UAGCACCAUCUGAAAUCGGUUA ptr miR-107 AGC AGCAUUGU AC AGGGCUAUC A c& miR 29b UAGCACCAUUUGAAAUCAGUGUU ptr-miR-1224-3p CCCCACCUCCUCUCUCCUCAG cfe miR-29c UAGCACCAUUUGAAAUCGGUUA ptr-miR-1224-5p GUGAGGACUCGGGAGGUGGAGGGU o& miR 30a UGUAAACAUCCUCGACUGGAAGC ptr-miR-1226 UCACCAGCCCUGUGUUCCCUAG cfa miR-30b UGUAAACAUCCUACACUCAGCU ptr πuR-124a UUAAGGCACGCGGUGAAUGCCA cfa-miR-30c UGUAAACAUCCUACACUCUCAGCU ptr-itnR-125b UCCCUGAGACCCUAACUUGUGA cfa miR-30d UGUAAACAUCCCCGACUGGAAGCU ptr-mιR-127 UCGG AUCCGUCUG AGCUUGGCU cfa-miR-30e CUUUCAGUCGGAUGUUUACAGC ptr miR 128 UCACAGUGAACCGGUCUCUUUU cfa-miR 31 AGGCAAGAUGCUGGCAUAGCUGU ptr-miR-133a UUGGUCCCCUUCAACCAGCUG cfa miR-32 UAUUGCACAUUACUAAGUUGCAU ptr-miR-135 UAUGGCUUUUUAUUCCUAUGUGA cfa-miR-320 AAAAGCUGGGUUGAGAGGGCQA ptr-πuR-136 ACUCCAUUUGUUUUOAUGAUGGA cfa-miR-323 CACAUUACACGGUCGACCUCU ptr-miR-140 AGUGGUUUUACCCUAUGGUAG cfa-miR-328 CUGGCCCUCUCUGCCCUUCCGU ptr-iraR-143 UGAGAUG AAGCACUGUAGCUCA cfa-miR-329 AGAGGUUUUCUGGGUUUCUGUUU ptr miR 144 UACAGUAUAGAUGAUGUACUAG cfa-miR-33 GUGCAUUGUAGUUGCAUUGC ptr-miR-145 GUCCAGUUUUCCCAGGAAUCCCUU cfa-miR-335 UCAAGAGCAAUAACGAAAAAUGU ptr miR-147 GUGUGUGGAAAUGCUUCUGC cfa miR-338 UCCAGCAUCAGUCAUUUUGUUGA ptr-miR- 154 UAGOUU AUCCGUOUUOCCUUCG cfa-miR-342 UCUCACACAGAAAUCGCACCCGU ptr-miR-15a UAGCAGCACAUAAUGGUUUGUG cfa miR-345 CCUGAACUAGGGGUCUGGAGG ptr-miR-15b UAGCAGCACAUCAUGGUUUACA cfa-miR-34a UGGCAGUGUCUUAGCUGGUUGU ptr-miR- 16 UAGCAGC ACGU AAAU AUUGGCG cfa-miR-34c AGGCAGUGUAGUUAGCUGAUUGC ptr-miR-17-3p ACUGCAGUGAAGGCACUUGU cfc-miR-350 UUCACAAAGCCCAUACACUUUU ptr-miR-17-5p CAAAGUGCUUACAGUGCAGGUAGU cfa miR-361 UUAUCAGAAUCUCCAGGGGUAC ptr imR lβ UAAGGUGCAUCUAGUGCAGAUA cfa-miR-363 AAUUGCACGGUAUCCAUCUGUAA ptr miR 181a AACAUUCAACGCUGUCGGUGAGU cfa miR 365 UAAUGCCCCUAAAAAUCCUUAU ptr-miR- 181a* ACCAUCGACCGUUOAUUGUACC cfa-miR-369 AAUAAUACAUGGUUOGUCUUU ptr-miR-181b AACAUUCAUUGCUGUCGGUGGGUU cfa-miR-374a UUAUAAUACAACCUGAUAAGU ptr-miR- 181c AACAUUC AACCUGUCGGUGAGU ofa miR-374b AUAUAAUACAACCUGCUAAGUG ptr-miR-183 UAUGGCACUGGUAGAAUUCACUG cfa-miR-376 AUCAUAGAGGAAAAUCCACGU ptr-miR-184 UGGACGGAGAACUGAUAAGGOU cfa-miR-378 ACUOOACUUGGAGUCAGAAGGC ptr-miR-186 CAAAGAAUUCUCCUUUUGGGCUU cfa-miR-379 UGGUAGACUAUGGAACGUAGG ptr-miR-188 CAUCCCUUGCAUGGUGGAGGGU cfa miR-380 UAUGUAAUAUGGUCCACGUCU ptr miR 190 UGAUAUGUUUGAUAUAUUAGGU cfa miR 382 AAUCAUUCACGGACAACACUUU ptr-miR-194 UGUAACAGCAACUCCAUGIUGGA cfa-mlR-383 AGAUCAGAAGGUGAUUGUGGCU ptr-miR-196 UAGGUAGUUUCAUGUUGUUGGG cfa-miR-384 AUUCCUAGAAAUUGUUCACAAU ptr miR 197 UUCACCACCUUCUCCACCCAGC ofa miR-409 AAUGUUOCUCGUUGAACCCCU ptr-miR 198 GGUCCAGAGGGGAGAUAGG ofa miR-410 AAUAUAACACAGAUGGCCUGU ptr-miR-199a CCCAGUGUUCAGACUACCUGUUC cfa miR-41 1 AUAGUAGACCGUAUAGCGUACG ptr miR 19a UGUGCAAAUCUAUGCAAAACUGA ofa miR-421 AUCAACAGACAUUAAUUGGGCG ptr-miR-19b UGUGC AAAUCCAUGC AAAACUGA ofa miR-423a UGAGGGGCAGAGAGCGAGACUUU ptr miR 20 UAAAGUGCUUAUAGUGCAGGUA cfa miR-424 CAAAACGUGAGGCGCUGCUAU ptr-miR-204 UUCCCUUUGUCAUCCUAUGCCU ofa-miR-425 AAUGACACGAUCACUCCCGUUGA ptr-miR-205 UCCUUCAUUCCACCGGAGUCUG cfa-miR-429 UAAUACUGUCUGGUAAUGCCGU ptr-miR-21 UAGCUUAUCAGACUGAUGUUGA cfa-miR-433 AUCAUGAUGGGCUCCUCGGUGU ptr-miR-214 ACAGC AGGCAC AGAC AGGCAG cfa-miR-448 UUGCAUAUGUAGGAUGUCCCAU ptτ-πuR-215 AUGACCU AUG AAUUGACAGAC cfa miR-449 UGGCAGUGUAUUGUUAGCUGGU ptr-rmR-216 UUAUCUCAQCUGGCAACUGUG cfa-miR-450a UUUUUGCGAUGUGUUCCUAAUA ptr-πuR-218 UUGUGCUUGAUCUAACCAUGU cfa-miR-450b UUUUGCAAUAUGUUCCUGAAU ptr-miR-22 AAGCUGCCAGUUGAAGAACUGU cfa-miR455 UAUGUGCCUUUGGACUACAUCG ptr-miR-220 CCACACCGUAUCUGACACUUU cfa-miR-485 AGAGGCUGGCCGUGAUGAAUUCG ptr-miR-223 UGUCAGUUUGUCAAAUACCCC cfa-miR-487 AAUCGUACAGGGUCAUCCACUU ptr-miR-224 CAAGUCACUAGUGGUUCCGUUUA ofa-miR-4θl CUUAUGCAAGAUUCCCUUCUA ptr-miR-23a AUCACAUUGCCAGGGAUUUCC cfa-miR-493 UGAAGGUCUACUGUGUGCCAG ptr-miR-23b AUCACAUUGCCAGGGAUUACCAC cfa-miR-495 AAACAAACAUGGUGCACUUCUU ptr-miR-24 UGGCUCAGUUCAGCAGGAACAG cfa-miR-497 CAGCAGCACACUGUGGUUUGU ptr-miR-25 CAUUGCACUUGUCUCGGCUGA cfa-nuR-499 UUAAGACUUGCAGUGAUGUUU ptr-miR-26a UUCAAGUAAUCCAGGAUAGGCU cfa-miR-500 AUGCACCUGGGCAAGGAUUCU ptr-miR-27a UUCACAGUGGCUAAGUUCCGCC cfa-miR-502 AAUGCACCUGGGCAAGGAUUCA ptr-miR-28 AAGGAGCUCACAGUCUAUUGAG cfa-miR-503 UAGCAGCGGGAACAGUACUG ptr-miR-29a CUAGCACCAUCUGAAAUCGGUU cfa-πuR-532 CAUGCCUUGAGUGUAGGACCGU ptr-miR-29b UAGCACCAUUUGAAAUCAGU cfa-miR-542 UGUGACAGAUUGAUAACUGAAA ptr miR-30a-3p CUUUCAGUCGGAUGUUUGCAGC cfa-miR-543 AAACAUUCGCGGUGCACUUCUU ptr-iruR-3Oa-5p UGUAAACAUCCUCGACUGGAAG cfa-miR-574 CACGCUCAUGCACACACCCACA ptr-miR-30b UGUAAACAUCCUACACUCAGC cfa-miR-590 UAAUUUUAUGUAUAAGCUAGU ptr-miR-30c UGUAAACAUCCUACACUCUCAGC cfa-miR-652 AAUGGCGCCACUAGGGUUGUGC ptr-miR-30d UGUAAACAUCCCCGACUGGAAG cfa-miR-660 UACCCAUUGCAUAUCGGAGUUG ptr-miR-31 GGCAAGAUGCUGGCAUAGCUG cfe-miR-664 UGGGCUAGGAAAAAUGAUUGGA ptr-miR-32 UAUUGCACAUUACUAAGUUGC cfa-miR-676 CUCUUCAAUCUCAGGACUCGC ptr miR 33 GUGCAUUGUAGUUGCAUUG cfa-πuR-7 UGGAAGACUAGUGAUUUUGUUGU ptr miR-34a UGGCAGUGUCUUAGCUGGUUGU cfe-miR-708 AAGGAGCUUACAAUCUAGCUGGG ptr-miR-506 UAAGGCACCCUUCUGAGUAGA cfa miR-9 UCUUUGGUUAUCUAGCUGUAUGA ptr-miR-507 UUUUGCACCUUUUGGAGUGAA cfa-miR-92a UAUUGCACUUGUCCCGGCCUGU ptr-miR-508 UGAUUGUAGCCUUUUUGAGUAGA cfa-miR-92b UAUUGCACUCGUCCCGGCCUCC ptr-miR-509a UGAUUGGUACGUCUGUGGAUAGA cfa-miR-93 CAAAGUGCUGUUCGUGCAGGUAG ptr-miR-509b UGAUUGGUACGUCUGUGAGUAGA cfa miR-98 UGAGGUAGUAAGUUGUAUUGUU ptr-nuR-510 UACCCAGGAGAGUGGCAAUCACA cfa-miR-99a AACCCGUAGAUCCGAUCUUGU ptr-miR S 13a UUCACAGGGAGGUGUCAUUUAU ofa-miR-99b CACCCGUAGAACCGACCUUGCG ptr-miR-513b UUCACAAGGAGAUGUCAUUUAU cin-let-7a UGAGGUAGUAGGUUAUGCAGU ptr-miR-S14 AUUGACACUUCUGUGAGUAG oin let 7b UGAGGUAGUAGGUUAUGUUGUU ptr-miR-7 UGGAAGACUAGUGAUUUUGUU om-let-7o UGAGGUAGUAGGUUAUAUCAGU ptr-nuR-9 UCUUUGGUUAUCUAGCUGUAUGA oin let-7d UGAGGUAGUUGGUUGUAUUGUU ptr-πuR-92 UAUUGCACUUGUCCCGGCCUGU cin let 7e UGAGGUAGUUGGUUGUAUCGGU ptr-miR-93 AAAGUGCUGUUCGUGCAGGUAG cin miR 101 UACAGUACUGUGAUAAAUAUUU ptr-miR-95 UUCAACGGGUAUUUAUUGAGCA oin miR-124 UAAGGCACGCGGUGAAUGCCAA ptr-miR-96 UUUGGCACUAGCACAUUUUUGC oin miR-126 UCGUACCGUGAGUAAUAAAGC ptr-miR-98 UGAGGUAGUAAGUUGUAUUGUU oin-miR-133 UUGGUCCCCUUCAACCAGCUG ptr-miR-99a AACCCGUAGAUCCGAUCUUGUG oin miR-141 UAACACUGUCUGGUAAAGAUGC rlcv-miR-rLl-1 UAACCUGAUCAGCCCCGGGGUU cin-miR-1473 UCAAGCUCGGGUUUAUGGGUGU rlcv-miR-rLl-10 UAGUGCQCCGGUGACCUGAUAG cin-miR-1497 UUGAAGAAUUGCAGGUGGUAGGU rlcv-miR-rLl-11 UGACACUCGAUAGGAUACGGGG cm-miR-153 UUGCAUAGUAACAAAAGUGAUC rlcv-miR-rLl-12-3p AACGGUGCAUGGACUGGCUAGA oin-miR-155 UUAAUGCUAAUAGUGAUAGGG rlov-miR-rLl-12-5p AGACCAGACCAUGCACAGUGGG cin-miR-181 AACAUUCAACCUGUCGAGCAAG rlcv-miR-rLl-13 GAUCAUAGCCAGUGUCCAGGGA cin-miR-183 UAUGGCACUGGUAGAAUUCACUG rlcv-miR-rLl - 14-3p UCGCACAUCAGGCUGAACGAC cin-miR-184 UGGACGGAGAACUGAUAAGGGC rlcv-miR-rLl- 14-5p UCGGACGGUCUGGUGCGCUUGAU cin miR-199-3p ACAGUAGUCUGCACAUUGGGUG ricv-miR-rLl-15 UCCUGUAGAGUAUGGGUGUGGUUU ciπ-miR-200 UAAUACUGCCUGGUAAUGGUGA rlcv-miR-rLl-16-3p CAUGAAACACAUGGCCUGUUCC cin-miR-216 UAAUCUCAGCUGGCAAUCUGUGA rlcv-miR-rLl -16-Sp AGCAGGCAUGUCUUCAUUCC cin-m]R-217 UACUGCAUUAGGAACUGAUUGG rlcv-miR-rLl-2 UAUCUUUUGCGGGGGAAUUUCCA cin-miR-219 UGAUUGUCCAAACGCAAGCUCAG rlov-miR rLl 3 CGCACCUCGCCGUCUCUACUGCU cin-miR-281 UGUCAUGGAGUUGCUCUCUUAUU rlov-miR-rLl-4-3p CACCACACGAUCCACUAGGUCU cin-miR-31 UGGCAAGAUGUUGGCAUAGCUA rlev-miR-rLl -4-Sp ACCUAGUAAUUGUGCGGUGUU oin-miR-33 GUGCAUUGUAGUUGCAUUG rlov-miR-rLl-5-3p CGCACCACUUUUCACUAGGUGU cin miR-34 AGGCAGUGUAGUUAGCUAGUUG rlov-miR-rLl-5-5p AACCUAGUGCCGGUGAUGUGCU cin-miR-672 UGAGUUUGGUGUACUGUGUGUU rlov-miR-rLl 6 UAGCACCGCUAUCCACUAUGUC cm-πiiR-7 UGGAAGACUAGUGAUUUUGUUG rlov-πuR-rLl-β 5p UUUAGUGGAAGUGACGUGCUGUG cin-raiR-78 UGGAGGCCUGGUUGUUUCCUG rlov miR rLl -7 CGAGGUAAACAUCGGCUUACUG cin-miR-92a UAUUGCACUUGUCCCGGUCUU rlov-miR-rLl-8 UAAGGUGAAUAUAGCUGCCCAUUG cm-miR-92b UAUUGCACUUGUCCCGGCCUU rlov-miR-rLl-9 UCGAUGCAUGGUCCCCCCUUAGU cm-miR-92c UAUUGCACUCGUCCCGGUCUAU rno-let-7a UGAGGUAGUAGGUUGUAUAGUU csa-let-7a UGAGGUAGUAGGUUAUAUCAGU rno-let-7b UGAGGUAGUAGGUUGUGUGGUU osa-let-7b UGAGGUAGUAGGUUAUGUUGUU rao-let-7b* CUAUACAACCUACUGCCUUCCC csa-let-7c UGAGGUAGUAGGUUAUGCAGUU rno-let-7o UGAGGUAGUAGGUUGUAUGGUU csa-let-7d UGAGGUAGUUGGUUGUAUUGUU mo-let-7d AGAGGUAGUAGGUUGCAUAGUU csa-miR-124 UAAGGCACGCGGUGAAUGCCAA rno-let-7d* CUAUACGACCUGCUGCCUUUCU csa-miR-126 UCGUACCGUGAGUAAUAAAGC mo-let-7e UGAGGUAGGAGGUUGUAUAGUU osa-miR-133 UUGGUCCCCUUCAACCAGCUA mo let-7e* CUAUACGGCCUCCUAGCUUUCC osa-mιR-141 UAACACUGUCUGGUAAAGAUGC rno-let-7f UGAGGUAGUAGAUUGUAUAGUU osa πuR 1473 UCAAGCUCGGUUUUAUGGGUGC rno-let-7i UGAGGUAGUAGUUUGUGCUGUU csa-miR-1497 UUGAAGAAUUGCAGGUGGUAGGU rno-let-7i* CUGCGCAAGCUACUGCCUUGCU osa-miR-153 UUGCAUAGUAAUAAAAGUGAUC rao-miR-1 UGGAAUGUAAAGAAGUGUGUAU osa-miR-155 UUAAUGCUAAUAAGUGAUUUAUG rno-miR-1* GCACAUACUUCUUUAUGUACCC osa-miR-183 UAUGGCACUAGUAGAAAUCACUG mo-miR-100 AACCCGUAGAUCCGAACUUGUG csa-miR-200 UAAUACUGCCUGGUAAUGAUGA mo-miR-101a UACAGUACUGUGAUAACUGAA csa-miR-216a UAAUCUCAGCUGGCAAUCUGUGA mo-miR-101a* UCAGUUAUCACAGUGCUGAUGC osa πuR-216b UAAUCUCUGCAGGCAACUGUGA mo-miR-101b UACAGUACUGUGAUAGCUGAA csa-miR-217 UACUGCAUUAGGAACUGAUUGG mo-miR-103 AGCAGCAUUGUACAGGGCUAUGA csa-πuR-219 UGAUUGUCCAAACGCAAUACA mo miR-106b UAAAGUGCUGACAGUGCAGAU csa-πuR-281 UGUCAUGGAGUUGCUCUCUCAUU mo-miR-106b* CCGCACUGUGGGUACUUGCUGC csa-miR-31 UGGCAAGAUGUUGGCAUAGCU mo-miR-107 AGCAGCAUUGUACAGGGCUAUCA csa-rraR-34 AGGCAGUGUAGUUAGCUAGUUG rno-miR-10a-3p CAAAUUCGUAUCUAGGGGAAUA csa-miR-7 UGGAAGACUAGUGAUUUUGUUGU mo-miR 10a-5p UACCCUGUAGAUCCGAAUUUGUG csa-miR-92a UAUUGCACUUGUCCCGGUCUA mo-miR-10b CCCUGUAGAACCGAAUUUGUGU csa-rmR-92ti UAUUGCACUUGUCCCGGUCUU mo miR-122 UGGAGUGUGACAAUGGUGUUUG csa-πnR-92c UAUUGCACCUGUCCCGGCCGAU mo miR 124 UAAGGCACGCGGUGAAUGCC dme-bantam UGAGAUCAUUϋUGAAAGCUGAUU mo-miR-124* CGUGUUCACAGCGGACCUUGAU dme-let-7 UGAGGUAGUAGGUUGUAUAGU mo-miR-125a-3p ACAGGUGAGGUUCUUGGGAGCC dme-miR-1 UGGAAUGUAAAGAAGUAUGGAG rno-miR-125a-5p UCCCUGAGACCCUUUAACCUGUGA dme-miR-10 ACCCUGUAGAUCCGAAUUUGU mo-nuR-125b* ACAAGUCAGGCUCUUGGGACCU dme-miR-100 AACCCGUAAAUCCGAACUUGUG rao-miR-125b-3p ACGGGUUAGGCUCUUGGGAGCU dme-miR-10O0 AUAUUGUCCUGUCACAGCAGU mo-miR-125b-5p UCCCUGAGACCCUAACUUGUGA dme-miR-1001 UGGGUAAACUCCCAAGGAUCA mo-miR-126 UCGUACCGUGAGUAAUAAUGCG dme-πuR-1002 UUAAGUAGUGGAUACAAAGGGCGA mo-miR-126* CAUUAUUACUUUUGGUACGCG dme-πuR-1003 UCUCACAUUUACAUAUUCACAG mo-miR-127 UCGGAUCCGUCUGAGCUUGGCU drae-miR-1004 UCUCACAUCACUUCCCUCACAG mo-miR-128 UCACAGUGAACCGGUCUCUUU dme-miR-1005 UCUGGAAUCUUUAAUUCGCAG mo-miR-129 CUUUUUGCGGUCUGGGCUUGC dme-miR-1006 UAAAUUCGAUUUCUUAUUCAUAG rno-πuR-129* AAGCCCUUACCCCAAAAAGCAU dme-raiR-1007 UAAGCUCAAUUAACUGUUUGCA mo-imR-130a CAGUGCAAUGUUAAAAGGGCAU dme-miR-1008 UCACAGCUUUUUGUGUUUACA rno-raiR-130b CAGUGCAAUGAUGAAAGGGCAU dme-miR-1009 UCUCAAAAAUUGUUACAUUUCAG rao-miR-132 UAACAGUCUACAGCCAUGGUCG dme-miR-1010 UUUCACCUAUCGUUCCAUUUGCAG rno-miR-133a UUUGGUCCCCUUCAACCAGCUG dme-miR-1011 UUAUUGGUUCAAAUCGCUCGCAG rno-miR-133b UUUGGUCCCCUUCAACCAGCUA dme-miR 1012 UUAGUCAAAGAUUUUCCCCAUAG mo-miR-134 UGUGACUGGUUGACCAGAGGGG dme-miR-1013 AUAAAAGUAUGCCGAACUCG mo-miR-135a UAUGGCUUUUUAUUCCUAUGUGA dmβ miR 1014 AAAAUUCAUUUUCAUUUGCAG rno-miR-135a* UGUAGGGAUGGAAGCCAUGAAA dme-miR-1015 UCCUGGGACAUOUCUCUUGCAG mo-πuR-135b UAUGGCUUUUCAUUCCUAUGUGA dme miR-1016 UUCACCUCUCUCCAUACUUAG rno-miR-136 ACUCCAUUUGUUUUGAUGAUGGA dme-miR-1017 GAAAGCUCUACCCAAACUCAUCC mo miR-136* CAUCAUCGUCUCAAAUGAGUCU dme-miR-11 CAUCACAGUCUGAGUUCUUGC mo-raiR-137 UUAUUGCUUAAGAAUACGCGUAG dme-miR-12 UGAGUAUUACAUCAGGUACUGGU rno-miR-138 AGCUGGUGUUGUGAAUCAGGCCG dme-miR-124 UAAGGCACGCGGUGAAUGCCAAG mo-miR-138* CGGCUACUUCACAACACCAGGG dme-miR-125 UCCCUGAGACCCUAACUUGUGA mo-miR 139 3p UGGAGACGCGGCCCUGUUGGAG dme-miR-133 UUGGUCCCCUUCAACCAGCUGU mo-πuR-139 5p UCUACAGUGCACGUGUCUCCAG dme-miR-137 UAUUGCUUGAGAAUACACGUAG mo-miR-140 CAGUGGUUUUACCCUAUGGUAG dme-miR-13a UAUCACAGCCAUUUUGAUGAGU mo raiR 140* UACCACAGGGUAGAACCACGG dme-miR-13b UAUCACAGCCAUUUUGACGAGU mo miR-141 UAACACUGUCUGGUAAAGAUGG dme-miR-14 UCAGUCUUUUUCUCUCUCCUA mo-miR-142-3p UGUAGUGUUUCCUACUUUAUGGA dme-miR-184 UGGACGGAGAACUGAUAAGGGC mo-miR-142-5p CAUAAAGUAGAAAGCACUACU dme-miR-184* CCUUAUCAUUCUCUCGCCCCG mo-miR-143 UGAGAUGAAGCACUGUAGCUCA dme-miR-190 AGAUAUGUUUGAUAUUCUUGGUUG mo-mιR-144 UACAGUAUAGAUGAUGUACU dme-miR-193 UACUGGCCUACUAAGUCCCAAC mo-miR-145 GUCCAGUUUUCCCAGGAAUCCCU dme-miR-210 UUGUGCGUGUGACAGCGGCUA mo-miR-146a UGAGAACUGAAUUCCAUGGGUU dme-m]R-219 UGAUUGUCCAAACGCAAUUCUUG mo miR-146b UGAGAACUGAAUUCCAUAGGCUGU dme-raiR-252 CUAAGUACUAGUGCCGCAGGAG mo-miR-147 GUGUGCGGAAAUGCUUCUGCUA dme-miR-263a GUUAAUGGCACUGGAAGAAUUCAC rno-miR-148b-3p UCAGUGCAUCACAGAACUUUGU dme-miR-263b CUUGGCACUGGGAGAAUUCAC mo-miR-14Sb-5p GAAGUUCUGUUAUACACUCAGG dme-miR-274 UUUUGUGACCGACACUAACGGGUAAU mo-miR-150 UCUCCCAACCCUUGUACCAGUG dme-miR-275 UCAGGUACCUGAAGUAGCGCGCG tno-miR-151 UCGAGGAGCUCACAGUCUAGU dme-miR-276* CAGCGAGGUAUAGAGUUCCUACG rno-miR-151* CUAGACUGAGGCUCCUUGAGG dme-miR-276a UAGGAACUUCAUACCGUGCUCU mo-miR-152 UCAGUGCAUGACAGAACUUGG dme-miR-276b UAGGAACUUAAUACCGUGCUCU mo-imR-153 UUGCAUAGUCACAAAAGUGAUC dme-miR-277 UAAAUGCACUAUCUGGUACGACA mo-miR-154 UAGGUUAUCCGUGUUGCCUUCG dme-miR-278 UCGGUGGGACUUUCGUCCGUUU mo-tniR-15b UAGCAGCACAUCAUGGUUUACA drae-miR-279 UGACUAGAUCCACACUCAUUAA mo-miR-16 UAGCAGCACGUAAAUAUUGGCG dmc-miR-280 UGUAUUUACGUUGCAUAUGAAAUGAUA mo-miR-17 CAAAGUGCUUACAGUGCAGGUAG dme-miR 281 UGUCAUGGAAUUGCUCUCUUUGU rno-miR-17-3p ACUGCAGUGAAGGCACUUGUGG drae-miR-281-1* AAGAGAGCUGUCCGUCGACAGU rao-πuR-17-5p CAAAGUGCUUACAGUGCAGGUAG dme-miR-281-2* AAGAGAGCUAUCCGUCGACAGU mo-miR-181a AACAUUCAACGCUGUCGGUGAGU dme-miR 282 AAUCUAGCCUCUACUAGGCUUUGUCUGU rno-miR-181a* ACCAUCGACCGUUGAUUGUACC dme-miR-283 UAAAUAUCAGCUGGUAAUUCU mo-πuR-181b AACAUUCAUUGCUGUCGGUGGGU dme miR 284 UGAAGUCAGCAACUUGAUUCCAGCAAUUG mo-miR-lSlc AACAUUCAACCUGUCGGUGAGU dme miR-28S UAGCACCAUUCGAAAUCAGUGC mo-miR-181d AACAUUCAUUGUUGUCGGUGGGU dme-miR-286 UGACUAGACCGAACACUCGUGCU mo-miR-182 UUUGGCAAUGGUAGAACUCACACCG dme miR-287 UGUGUTJGAAAAUCGUUUGCAC rno-miR-183 UAUGGCACUGGUAGAAUUCACU dme miR 28S UUUCAUGUCGAUUUCAtTUUCAUG mo-miR-184 UGGACGGAGAACUGAUAAGGGU dme-miR-289 UAAAUAUUUAAGUGGAGCCUGCGACU mo-miR-185 UGGAGAGAAAGGCAGUUCCUGA dme-miR-2a UAUCACAGCCAGCUUUGAUGAGC mo-miR 186 CAAAGAAUUCUCCUUUUGGGCU dme-miR-2b UAUCACAGCCAGCUUUGAGGAGC mo-miR-187 UCGUGUCUUGUGUUGCAGCCGG dme-miR-2c UAUC AC AGCC AGCUUUGAUGGGC mo-miR-188 CAUCCCUUGCAUGGUGGAGGG dme-miR-3 UCACUGGGCAAAGUGUGUCUCA mo-miR 18a UAAGGUGCAUCUAGUGCAGAUAG dme-miR-303 UUUAGGUUUCACAGGAAACUGGU mo miR-190 UGAUAUGUUUGAUAUAUUAGGU dme-miR 304 UAAUCUCAAUUUGUAAAUGUGAG mo-miR-190b UGAUAUGUUUGAUAUUAGGUU dme-miR-305 AUUaUACUUCAUCAGGUQCUCUG rno-miR 191 CAACGG AAUCCCAAAAGC AGCUG dme-miR-306 UCAGGUACUUAGUGACUCUCAA mo-miR-192 CUGACCUAUGAAUUGACAGCC dme-miR-306* GGGGGUCACUCUGUGCCUGUGC mo-miR-193 AACUGGCCUACAAAGUCCCAGU dme-miR-307 UCACAACCUCCUUGAGUGAG mo-miR-193* UGGGUCUUUGCGGGCAAGAUGA dme-miR-308 AAUCACAGGAUUAUACUGUGAG mo-miR-194 UGUAACAGCAACUCCAUGUGGA drae-miR-309 GCACUGGGUAAAGUUUGUCCUA mo-miR-195 UAGCAGCACAGAAAUAUUGGC dme-miR-310 UAUUGCACACUUCCCGGCCUUU rno-miR- 196a UAGGU AGUUUCAUGUUGUUGGG dme-miR-311 UAUUGCACAUUCACCGGCCUGA rno-πuR-196a* UCGGCAACAAGAAACUGCCUGA dme-miR-312 UAUUGCACUUGAGACGGCCUGA rno-πuR-196b UAGGUAGUUUCCUGUUGUUGGG dme-miR-313 UAUUGCACUUUUCACAGCCCGA mo-miR-196c UAGGUAGUUUCGUGUUGUUGGQ dme-πuR-314 UAUUCGAGCCAAUAAGUUCGG mo-miR-199a-3p ACAGUAGUCUGCACAUUGGUUA dme-πuR-315 UUUUGAUUGUUGCUCAGAAAGC mo-imR-199a-5p CCCAGUGUUCAGACU ACCUGUUC dme miR-316 UGUCUUUUUCCGCUUACUGGCG tno-miR-19a UGUGCAAAUCUAUGCAAAACUGA dme-miR-317 UGAACACAGCUGGUGGUAUCCAGU mo-πuR-19b UGUGCAAAUCCAUGCAAAACUGA dme-πuR-318 UCACUGGGCUUUGUUUAUCUCA mo-miR-200a UAACACUGUCUGGUAACGAUGU dme-miR-31a UGGCAAGAUGUCGGCAUAGCUGA mo-miR-200b UAAUACUGCCUGGUAAUGAUGAC dme-nuR-31b UGGCAAGAUGUCGGAAUAGCUG rno-miR-200c UAAUACUGCCGGGUAAUGAUGG dme-miR-33 AGGUGCAUUGUAGUCGCAUUG mo-miR-203 GUGAAAUGUUUAGGACCACUAG dme-miR-34 UGGCAGUGUGGUUAGCUGGUUGUG mo-miR-204 UUCCCUUUGUCAUCCUAUGCCU dme-miR-375 UUUGUUCGUUUGGCUUAAGUUA mo-miR-204* GCUGGGAAGGCAAAGGGACGUU dme-miR-4 AUAAAGCUAGACAACCAUUGA mo-miR-205 UCCUUCAUUCCACCGGAGUCUG dme-miR-S AAAGGAACGAUCGUUGUGAUAUG mo-miR-206 UGGAAUGUAAGGAAGUGUGUGG dtne-miR-6 UAUCACAGUGGCUGUUCUUUUU mo-miR-207 GCUUCUCCUGGCUCUCCUCCCUU dme-miR-7 UGGAAOACUAGUGAUUUUGUUGU mo-miR-208 AUAAGACGAGCAAAAAGCUUGU dme-miR-79 UAAAGCUAGAUUACCAAAGCAU rno-miR-20a UAAAGUGCUUAUAGUGCAGGUAG dme-miR-8 UAAUACUGUCAGGUAAAGAUGUC mo-miR-20a* ACUGCAUUACGAGCACUUACA dme-miR-87 UUGAGCAAAAUUUCAGGUGUG mo-miR-20b-3p ACUGCAGUGUGAGCACUUCUGG dme-πnR-927 UUUAGAAUUCCUACGCUUUACC rno-miR-20b-5p CAAAGUGCUCAUAGUGCAGGU dme miR-929 CUCCCUAACGGAGUCAGAUUG rao-miR-21 UAGCUUAUCAGACUGAUGUUGA dme-rruR-92a CAUUGCACUUGUCCCGGCCUAU mo-miR-21* C AACAGC AGUCGAUGGGCUGUC dme-miR-92b AAUUGCACUAGUCCCGGCCUGC rno-πuR-210 CUGUGCGUGUGACAGCGGCUGA dme-miR-932 UCAAUUCCGUAGUGCAUUGCAG mo-miR-211 UUCCCUUUGUCAUCCUUUGCCU dme-miR-954 UCUGGGUGUUGCGUUGUGUGU mo-πuR-212 UAACAGUCUCCAGUCACGGCCA dme-miR-955 CAUCGUGCAGAGGUUUGAGUGUC rno-πuR-214 ACAGCAGGCACAGACAGGCAG dme-nuR-956 UUUCGAGACCACUCUAAUCCAUU rao-miR-215 AUGACCUAUGAUUUGACAGAC dme-miR-957 UGAAACCGUCCAAAACUGAGGC mo-nuR-216a UAAUCUC AGCUGGCAACUGUG A dme-miR-958 UGAGAUUCUUCUAUUCUACUUU mo-miR-217 UACUGCAUCAGGAACUGACUGGAU dme-miR-959 UUGUCAUCGGGGGUAUUAUGAA rno-miR-218 UUGUGCUUGAUCUAACCAUGU dme-miR-960 UGAGUAUUCCAGAUUGCAUAGC rao-miR-218* CAUGGUUCUGUCAAGCACCGCG dme-miR-961 UUUGAUCACCAGUAACUGAGAU rao-miR^lθ-l-Sp AGAGUUGCGUCUGGACGUCCCG dme-miR-962 AUAAGGUAGAGAAAUUGAUGCUGUC mo-miR-219-2-3p AGAAUUGUGGCUGGACAUCUGU dme-miR-963 ACAAGGUAAAUAUCAGGUUGUUUC mo-miR-219-5p UGAUUGUCC AAACGC AAUUCU drae-miR-964 UUAGAAUAGGGGAGCUUAACUU mo-miR-22 AAGCUGCCAGUUGAAGAACUGU dme-miR-965 UAAGCGUAUAGCUUUUCCCCUU mo-miR-22* AGUUCUUCAGUGGCAAGCUUUA dme-miR-966 UGUGGGUUGUGGGCUGUGUGG rno-miR-221 AGCUACAUUGUCUGCUGGGUUUC dme-miR-967 AGAGAUACCUCUGGAGAAGCG rno-miR-222 AGCUACAUCUGGCUACUGGGU dme-miR-968 UAAGUAGUAUCCAUUAAAGGGUUG mo-miR-223 UGUCAGUUUGUCAAAUACCCC dme-miR-969 GAGUUCCACUAAGCAAGUUUU mo-miR-224 CAAGUCACUAGUGGUUCCGUUUA dme-miR-970 UCAUAAGACACACGCGGCUAU mo-miR-23a AUCACAUUGCCAGGGAUUUCC dme-miR-971 UUGGUGUUACUUCUUACAGUGA mo-miR-23a* GGGGUUCCUGGGGAUGGGAUUU dmc-nuR-972 UGUACAAUACGAAUAUUUAGGC mo-miR-23b AUCACAUUGCCAGGGAUUACC dme-miR-973 UGGUUGGUGGUUGAACUUCGAUUUU rao-miR-24 UGGCUCAGUUCAGCAGGAACAG dme-miR-974 AAGCGAGCAAAGAAGUAGUAUU mo-miR-24-1* GUGCCUACUGAGCUGAUAUCAG dme-miR-975 UAAACACUUCCUACAUCCUGUAU mo-miR-24-2* GUGCCUACUGAGCUGAAACAGU dme-miR-976 UUGGAUUAGUUAUCAUCAAUGC rao-miR-25 CAUUGCACUUGUCUCGGUCUGA dme-miR-977 UGAGAUAUUCACGUUGUCUAA mo-miR-25* AGGCGGAGACACGGGCAAUUGC dme-miR-978 UGUCCAGUGCCGUAAAUUGCAG mo-πuR-26a UUCAAGUAAUCCAGGAUAGGCU dme-miR-979 UUCUUCCCGAACUCAGGCUAA mo-miR-26b UUCAAGUAAUUCAGGAUAGGU dme-miR-980 UAGCUGCCUUGUGAAGGGCUUA mo-miR-26b* CCUGUUCUCCAUUACUUGGCUC dme-miR-981 UUCGUUGUCGACGAAACCUGCA rno-miR-27a UUCACAGUGGCUAAGUUCCGC dme-miR-982 UCCUGGACAAAUAUGAAGUAAAU mo-miR-27a* AGGGCUUAGCUGCUUGUGAGCA dme-miR-983 AUAAUACGUUUCGAACUAAUGA mo-miR-27b UUCACAGUGGCUAAGUUCUGC dme-miR-984 UGAGGUAAAUACGGUUGGAAUUU mo-miR-28 AAGGAGCUCACAGUCUAUUGAG dme-miR-98S CAAAUGUUCCAAUGGUCGGGCA mo-miR-28* CACUAGAUUGUGAGCUCCUGGA dme-miR-986 UCUCGAAUAGCGUUGUGACUGA rao-miR-290 CUCAAACUAUGGGGGCACUUUUU dme-miR-987 UAAAGUAAAUAGUCUGGAUUGAUG mo-miR-291a-3p AAAGUGCUUCCACUUUGUGUGCC dme-miR-988 CCCCUUGUUGCAAACCUCACGC rao-miR-291a-5p CAUCAAAGUGGAGGCCCUCUCU dme-miR-989 UGUGAUGUGACGUAGUGGAAC rao-miR-292-3p AAGUGCCGCCAGGUUUUGAGUGU dme-miR-990 AUUCACCGUUCUGAGUUGGCC mo-imR-292-5p ACUCAAACUGGGGGCUCUUUUG dme-miR-991 UUAAAGUUGUAGUUUGGAAAGU mo-miR-296 GAGGGUUGGGUGGAGGCUCUCC dme-miR-992 AGUACACGUUUCUGGUACUAAG rno-miR 296* AGGGCCCCCCCUCAAUCCUGU dme-miR-993 GAAGCUCGUCUCUACAGGUAUCU mo-ttnR-297 AUGUAUGUGUGCAUGUAUGCAUG dme-miR-994 CUAAGGAAAUAGUAGCCGUGAU mo-miR-298 GGCAGAGGAGGGCUGUUCUUCCC dme-πuR-995 UAGCACCACAUGAUUCGGCUU mo-miR-299 UGGUUUACCGUCCCACAUACAU dme-miR-996 UGACUAGAUUUCAUGCUCGUCU mo-miR-29a UAGCACCAUCUGAAAUCGGUUA dme-miR-997 CCCAAACUCGAAGGAGUUUCA mo-πuR-29a* ACUGAUUUCUUUUGGUGUUCAG dme-miR-998 UAGCACCAUGAGAUUCAGCUC mo-nuR-29b UAGCACCAUUUGAAAUCAGUGUU dme-miR-999 UGUUAACUGUAAGACUGUGUCU mo-miR-29b-l * UUUCAUAUGGUGGUUUAGAUUU dme-miR-9a UCUUUGGUUAUCUAGCUGUAUGA rao-miR-29b-2* CUGGUUUCACAUGGUGGCUUAG dme-miR-9b UCUUUGGUGAUUUUAGCUGUAUG rao-miR-29c UAGCACCAUUUGAAAUCGGUUA dme-miR-9o UCUUUGGUAUUCUAGCUGUAGA mo-miR-29c* UGACCGAUUUCUCCUGGUGUUC dme-ituR-iab-4-3p CGGUAUACCUUCAGUAUACGUAAC rno-miR-300-3p UAUGCAAGGGCAAGCUCUCUUC dme-miR-iab-4-5p ACGUAUACUGAAUGUAUCCUGA mo-πuR-300-Sp UUGAAGAGAGGUUAUCCUUUGU dme-miR-iab-4as-3p GGAUACAUUCAGUAUACGUUUA rno-miR-301a CAGUGCAAUAGUAUUGUCAAAGC dme-n)iR-iab-4as-Sp UUACGUAUACUGAAGGUAUACCG rno-imR-301b CAGUGCAAUGGUAUUGUCAAAGC dps bantam UGAGAUCAUUUUGAAAGCUGAUU rno-nJR-30a UGUAAACAUCCUCGACUGGAAG dps-let-7 UGAGGUAGUAGGUUGUAUAGU mo-miR-30a* CUUUCAGUCGGAUGUUUGCAGC dps-tniR-1 UGGAAUGUAAAGAAGUAUGaAG rno miR-30b-3p CUGGGAUGUGGAUGUUUACGUC dps-miR-10 ACCCUGUAGAUCCGAAUUUGU mo miR-30b-5p UGUAAACAUCCUACACUCAGCU dps-πuR-100 AACCCGUAAUUCCGAACUUGUG mo-miR-30c UGUAAACAUCCUACACUCUCAGC dps-miR-11 CAUCACAGUCUGAGUUCUUGC mo miR-30c-l* CUGGGAGAGGGUUGUUUACUCC dps-miR-12 UGAGUAUUACAUCAGGUACUGGU mo miR-30c-2* CUGGGAGAAGGCUGUUUACUCU dps-miR-124 UAAGGCACGCGGUGAAUGCCAAG rno-miR-30d UGUAAACAUCCCCGACUGGAAG dps miR-125 UCCCUGAGACCCUAACUUGUGA mo-miR-30d* CUUUCAGUCAGAUGUUUGCUGC dps-miR-133 UUGGUCCCCUUCAACCAGCUGU rno-πuR 3Oe UGUAAACAUCCUUGACUGGAAG dps-miR-13a UAUCACAGCCAUUUUGAUGAGU mo-πuR-30e* CUUUCAGUCGGAUGUUUACAGC dps-miR-Bb UAUCACAGCCAUUUUGACGAGU mo-miR-31 AGGCAAGAUGCUGGCAUAGCUG dps-miR-14 UCAGUCUUUUUCUCUCUCCUA mo-miR-32 UAUUGCACAUUACUAAGUUGCA dps-miR-184 UGGACGGAGAACUGAUAAGGGC mo-miR-320 AAAAGCUGGGUUGAGAGGGCGA dps-miR-210 UUGUGCGUGUGACAGCGGCUA mo-miR-322 CAGCAGCAAUUCAUGUUUUGGA dps-miR-219 UGAUUGUCCAAACGCAAUUCUUG rno-miR-322* AAACAUGAAGCGCUGCAACA dps-miR-263a GUUAAUGGCACUGGAAGAAUUCAC mo-miR-323 CACAUUACACGGUCGACCUCU dps-miR-263b CUUGGCACUGGGAGAAUUCAC mo raiR-323* AGGUGGUCCGUGGCGCGUUCGC dps-miR-274 UUUUGUGACCGACACUAACGGGUAAU rno-miR-324-3p CCACUGCCCCAGGUGCUGCUGG dps-miR-275 UCAGGUACCUGAAGUAGCGCGCG mo-miR-324-5p CGCAUCCCCUAGGGCAUUGGUGU dps-miR-276a UAGGAACUUCAUACCGUGCUCU mo-miR-325-3p UUUAUUGAGCACCUCCUAUCAA dps-miR-276b UAGGAACUUAAUACCGUGCUCU rno-miR-325-5p CCUAGUAGGUGCUCAGUAAGUGU dps-miR-277 UAAAUGCACUAUCUGGUACGACA mo-miR-326 CCUCUGGGCCCUUCCUCCAGU dps-miR-278 UCGGUGGGACUUUCGUCCGUUU mo-miR-327 CCUUGAGGGGCAUGAGGGU dps-miR-279 UGACUAGAUCCACACUCAUUAA rno-iniR-328 CUGGCCCUCUCUGCCCUUCCGU dps-miR-280 UGUAUUUACGUUGCAUAUGAAAUGAUA mo-miR-329 AACACACCCAGCUAACCUUUUU dps-miR-281 UGUCAUGGAAUUGCUCUCUUUGU rno-miR-33 GUGCAUUGUAGUUGCAUUGCA dps-πuR-282 AAUCUAGCCUCUACUAGGCUUUGUCUGU mo-miR-330 UCUCUGGGCCUGUGUCUUAGGC dps-miR-283 UAAAUAUCAGCUGGUAAUUCU mo-miR-330* GCAAAGCACAGGGCCUGCAGAGA dps-πuR-284 UGAAGUCAGCAACUUGAUUCCAGCAAUUG mo-miR-331 GCCCCUGGGCCUAUCCUAGAA dps-miR-285 UAGCACCAUUCGAAAUCAGUGC mo-πuR-333 GUGGUGUGCUAGUUACUUUU dps-miR-286 UGACUAGACCGAACACUCGUGCU rno-miR-335 UCAAGAGCAAUAACGAAAAAUGU dps-miR-287 UGUGUUGAAAAUCGUUUGCAC mo-miR 336 UCACCCUUCCAUAUCUAGUCU dps-miR-288 UUUCAUGUCGAUUUCAUUUCAUG mo-miR-337 UUCAGCUCCUAUAUGAUGCCUUU dps-miR 289 UAAAUAUUUAAGUGGAGCCUGCGACU rno-miR-338 UCCAGCAUCAGUGAUUUUGUUGA dps-πuR-2a UAUCACAGCCAGCUUUGAUGAGC rno-miR-338* AACAAUAUCCUGGUGCUGAGUG dps-πuR-2b UAUCACAGCCAGCUUUGAGGAGC mo-miR-339-3p UGAGCGCCUCGACGACAGAGCCA dps miR-2c UAUCACAGCCAGCUUUGAUGGGC mo-miR-339-5p UCCCUGUCCUCCAGGAGCUCACG dps-miR-3 UCACUGGGCAAAGUGUGUCUCA mo πuR-340-3p UCCGUCUCAGUUACUUUAUAGCC dps-miR-304 UAAUCUCAAUUUGUAAAUGUGAG mo-miR-340-5p UUAUAAAGCAAUGAGACUGAUU dps-mιR-305 AUUGUACUUCAUCAGGUGCUCUG mo-miR-341 UCGGUCGAUCGGUCGGUCGGU dps-miR-306 UCAGGUACUUAGUGACUCUCAA mo-miR-342-3p UCUCACACAGAAAUCGCACCCGU dps-miR-307 UCACAACCUCCUUGAGUGAG mo-miR-342-Sp AGGGGUGCUAUCUGUGAUUGAG dps-miR-308 AAUCACAGGAUUAUACUGUGAG mo-nuR-343 UCUCCCUCCGUGUGCCCAGA dps-miR-309 GCACUGGGUGAAGUUUGUCUUA rno-miR-344-3p UGAUCUAGCCAAAGCCUGACCGU dps-miR-314 UAUUCGAGCCAAUAAGUUCGG mo-miR-344-5p UCAGGCUCCUGGCUAGAUUCCAGG dps-miR-315 UUUUGAUUGUUGCUCAGAAAGC mo-miR-345-3p CCCUGAACUAGGGGUCUGGAGA dps-miR-316 UGUCUUUUUCCGCUUACUGGCG mo-miR-34S-5p UGCUGACCCCUAGUCCAGUGC dps-miR-317 UGAACACAGCUGGUGGUAUCCAAU mo-miR-346 UGUCUGCCUGAGUGCCUGCCUCU dps-miR-318 UCACUGGGCUUUGUUUAUCUCA πio-miR-347 UGUCCCUCUGGGUCGCCCA dps-miR-31a UGGCAAGAUGUCGGCAUAGCUGA mo-nuR-349 CAGCCCUGCUGUCUUAACCUCU dps-miR-31b UGGCAAGAUGUCGGAAUAGCUGA rno-miR-34a UGGCAGUGUCUUAGCUGGUUGU dps-miR-33 AGGUGCAUUGUAGUCGCAUUG rno-πuR-34b UAOGCAGUGUAAUUAGCUGAUUG dps-miR-34 UGGCAGUGUGGUUAGCUGGUUG mo-miR-34c AGGCAGUGUAGUUAGCUGAUUGC dps-miR-4 AUAAAGCUAGACAACCAUUGA rao-πnR-34o* AAUCACUAACCACACAGCCAGG dps-miR-5 AAAGGAACGAUCGUUGUGAUAUG mo-miR-350 UUCACAAAGCCCAUACACUUUCAC dps-miR-6 UAUCACAGUGGCUGUUCUUUUU rno-miR-351 UCCCUGAGGAGCCCUUUGAGCCUGA dps-miR-7 UGGAAGACUAGUGAUUUUGUUGU rao-miR-352 AGAGUAGUAGGUUGCAUAGUA dps-miR-79 UAAAGCUAGAUUACCAAAGCAU rno-miR-361 UUAUCAGAAUCUCCAGGGGUAC dps-miR-8 UAAUACUGUCAGGUAAAGAUGUC mo-miR-363 AAUUGCACGGUAUCCAUCUGUA dps-miR-87 UUGAGCAAAAUUUCAGGUGUG rno-tniR-363* CGGGUGGAUCACGAUGCAAUUU dp5-miR-92a CAUUGCACUUGUCCCGGCCUAU mo-miR-365 UAAUGCCCCUAAAAAUCCUUAU dps-miR-92b AAUUGCACUAGUCCCGGCCUGC mo-miR-369-3p AAUAAUACAUGGUUGAUCUUU dps-miR-9a UCUUUGGUUAUCUAGCUGUAUGA mo-miR-369-5p AGAUCGACCGUGUUAUAUUCGC dps-miR-9b UCUUUGGUGAUUUUAGCUGUAUG mo-miR-370 GCCUGCUGGGGUGGAACCUGGUU dps-miR-9o UCUUUGGUAUUCUAGCUGUAGA rαo miR-374 AUAUAAUACAACCUGCUAAGUG dps-miR-iab-4 3p CGGUAUACCUUCAGUAUACGUAAC πio-miR-375 UUUGUUCGUUCGGCUCGCGUGA dps-miR iab-4 5p ACGUAUACUGAAUGUAUCCUGA πio-miR-376a AUCGUAGAGGAAAAUCCACGU ebv-miR-B ARTlO UACAUAACCAUGGAGUUGGCUGU mo-miR-376a* GGUAGAUUCUCCUUCUAUGAG cbv-miR-BARTlO* GCCACCUCUUUGGUUCUGUACA rno-miR-376b-3p AUCAUAGAGGAACAUCCACUU ebv-miR-BARTll-3p ACGCACACCAGGCUGACUGCC mo-miR-376b-5p GUGGAUAUUCCUUCUAUGGUUA ebγ-πuR-BARTll-5p UCAGACAGUUUGGUGCGCUAGUUG rno-miR-376c AACAUAGAGGAAAUUUCACGU ebv-miR-BART12 UCCUGUGGUGUUUGGUGUGGUU mo miR 377 AUCACACAAAGGCAACUUUUGG ebv-miR-BART13 UGUAACUUGCCAGGGACGGCUGA rno miR-37S ACUGGACUUGGAGUCAGAAGG ebv-imR BARTl 3* AACCGGCUCGUGGCUCGUACAG mo-miR-378* CUCCUGACUCCAGGUCCUGUGU ebv miR BARTl-3p UAGCACCGCUAUCCACUAUGUC mo-miR-379 UGGUAGACUAUGGAACGUAGG ebv-miR BARTl₄ UAAAUGCUGCAGUAGUAGGGAU mo-miR-379* CUAUGUAACAUGGUCCACUAAC ebv ΠΠR-BART14* UACCCUACGCUGCCGAUUUACA rno-mιR-380 AUGGUUGACCAUAGAACAUGCG ebv miR-BART15 GUCAGUGGUUUUGUUUCCUUGA rno-nuR-381 UAUACAAGGGCAAGCUCUC ebv-miR-BARTl-5p UCUUAGUGGAAGUGACGUGCUGUG mo-miR-382 GAAGUUGUUCGUGGUGGAUUCG ebv-miR-BART16 UUAGAUAGAGUGGGUGUGUGCUCU mo-miR-382* AAUCAUUCACGGACAACACUU ebv-miR-BART17-3p UGUAUGCCUGGUGUCCCCUUAGU rao-mjR-383 AGAUCAGAAGGUGACUGUGGCU ebv-miR-BART17-5p UAAGAGGACGCAGGCAUACAAG mo-miR-384-3p AUUCCUAGAAAUUGUUCACAAU ebv-miR-BARTl 8-3p UAUCGGAAGUUUGGGCUUCGUC mo-miR-384-5p UGUAAACAAUUCCUAGGCAAUGU ebv-miR-BART18-5p UCAAGUUCGCACUUCCUAUACA rno-miR-409-3p AAUGUUGCUCGGUGAACCCC ebv-miR-BART19 3p UUUUGUUUGCUUGGGAAUGCU mo miR-409-Sp AGGUUACCCGAGCAACUUUG ebv-miR-BART19-5p ACAUUCCCCGCAAACAUGACAUG rno-miR-410 AAUAUAACACAGAUGGCCUGU ebv-miR-BART20-3p CAUGAAGGCACAGCCUGUUACC mo-miR-411 UAGUAGACCGUAUAGCGUACG ebv-miR-BART20-5p UAGCAGGCAUGUCUUCAUUCC rno-miR-412 ACUUCACCUGGUCCACUAGCCGU ebv-miR-BART2-3p AAGGAGCGAUUUGGAGAAAAUAAA rno-miR-421 GGCCUCAUUAAAUGUUUGUUG ebv-miR-BART2-5p UAUUUUCUGCAUUCGCCCUUGC mo-miR-423 AGCUCGGUCUGAGGCCCCUCAGU ebv-miR-BART3 CGCACCACUAGUCACCAGGUGU rao-miR-425 AAUGACACGAUCACUCCCGUUGA ebv-miR-BART3* ACCUAGUGUUAGUGUUGUGCU mo miR-429 UAAUACUGUCUGGUAAUGCCGU ebv-miR-BART4 GACCUGAUGCUGCUGGUGUGCU rao-miR-431 UGUCUUGCAGGCCGUCAUGCA ebv-miR-BART5 CAAGGUGAAUAUAGCUGCCCAUCG mo-miR-433 AUCAUGAUGGGCUCCUCGGUGU ebv-miR-BART6-3p CGGGGAUCGGACUAGCCUUAGA rao-miR-434 UUUGAACCAUCACUCGACUCCU ebv-miR-BART6-5p UAAGGUUGGUCCAAUCCAUAGG rno-miR-448 UUGCAUAUGUAGGAUGUCCCAU ebv-πuR-BART7 CAUCAUAGUCCAGUOUCCAGGG mo-miR-449a UGGCAGUGUAUUGUUAGCUGGU ebv-miR-BART7* CCUGaACCUUGACUAUGAAACA mo-miR-450a UUUUUGCGAUGUGUUCCUAAUG ebv-miR-BART8 UACGGUUUCCUAGAUUGUACAG mo-miR-451 AAACCGUUACCAUUACUGAGUU ebv-miR-BART8* GUCACAAUCUAUGGGGUCGUAGA mo miR-455 UAUGUGCCUUUGGACUACAUCG ebv-miR-BART9 UAACACUUCAUGGGUCCCGUAGU mo-miR-463 UGAUAGACGCCAAUUUGGGUAG ebv-miR-BART9* UACUGGACCCUGAAUUGGAAAC mo-miR-466b UAUGUGUGUGUGUAUGUCCAUG ebv-miR-BHRFl-1 UAACCUGAUCAGCCCCGGAGUU rno-πuR-466c UGUGAUGUGUGCAUGUACAUG ebv-miR-BHRFl-2 UAUCUUUUGCGGCAGAAAUUGA mo miR-471 UACGUAGUAUAGUGCUUUUCAC ebv-miR-BHKJFl-2* AAAUUCUGUUGCAGCAGAUAGC mo-miR-483 UCACUCCUCCCCUCCCGUCUUGU ebv-miR-BHRFl-3 UAACGGGAAGUGUGUAAGCACA mo-miR-484 UCAGGCUCAGUCCCCUCCCGAU gga-let-7a UGAGGUAGUAGGUUGUAUAGUU mo-nuR-485 AGAGGCUGGCCGUGAUGAAUUC gga let 7b UGAGGUAGUAGGUUGUGUGGUU mo-miR-487b AAUCGUACAGGGUCAUCCACU gga let 7o UGAGGUAGUAGGUUGUAUGGUU mo-miR-488 UUGAAAGGCUGUUUCUUGGUC gga let 7d AGAGGUAGUGGGUUGCAUAGU mo-miR-489 AAUGACAUCACAUAUAUGGCAGC gga let 7f UGAGGUAGUAGAUUGUAUAGUU mo-πuR-493 UGAAGGUCUACUGUGUGCCAG gga let 7g UGAGGUAGUAGUUUGUACAGU mo-miR-494 UGAAACAUACACGGGAAACCU gga-let-7i UGAGGUAGUAGUUUGUGCUGU rno-miR-495 AAACAAACAUGGUGCACUUCUU gga-let-7j UGAGGUAGUAGGUUGUAUAGUU mo-πuR-497 CAGCAGCACACUGUGGUUUGUA gga-let-7k UGAGGUAGUAGAUUGAAUAGUU mo-miR-499 UUAAGACUUGCAGUGAUGUUU gga-miR-100 AACCCGUAGAUCCGAACUUGUG mo-miR 500 AAUGCACCUGGGCAAGGGUUCA gga miR-101 UACAGUACUGUGAUAACUGAAG rno-miR-501 AAUCCUUUGUCCCUGGGUGAAA gga-miR-103 AGCAGCAUUGUACAGGGCUAUGA mo-miR-503 UAGCAGCGGGAACAGUACUGCAG gga-miR-106 AAAAGUGCUUACAGUGCAGGUA mo-miR-505 GUCAACACUUGCUGGUUUCC gga-miR-107 AGCAGCAUUGUACAGGGCUAUCA rno-πuR-532-3p CCUCCCACACCCAAGGCUUGCA gga-miR-10b UACCCUGUAGAACCGAAUUUGU rno-miR-532-5p CAUGCCUUGAGUGUAGGACUGU gga-raiR-122 UGGAGUGUGACAAUGGUGUUUGU mo-miR-S39 GGAGAAAUUAUCCUUGGUGUGU gga-miR-124a UUAAGGCACGCGGUGAAUGCCA mo-miR-540 AGGUCAGAGGUCGAUCCUGG gga-miR-124b UUAAGGCACGCAGUGAAUGCCA rno-miR 541 AAGGGAUUCUGAUGUUGGUCACACU gga miR-125b UCCCUGAGACCCUAACUUGUGA rno-miR-542-3p UGUGACAGAUUGAUAACUGAAA gga-miR-126 UCGUACCGUGAGUAAUAAUGCGC mo-miR-542-5p CUCGGGGAUCAUCAUGUCACGA gga-miR-126* CAUUAUUACUUUUGGUACGCO rno-miR-543 AAGUUGCCCGCGUGUUUUUCGC gga-miR-128 UCACAGUGAACCGGUCUCUUU mo-miR-543* AAACAUUCGCGGUGCACUUCU gga-πuR-130a CAGUGCAAUAUUAAAAGGGCAU πio-πnR-55 Ib GGCGACCCAUACUUGGUUUCAOU gga-miR-130b CAGUGCAAUAAUGAAAGGGCGU mo-imR-598-3p UACGUCAUCGUCGUCAUCGUUA gga-miR-133a UUGGUCCCCUUCAACCAGCUGU rno-miR-598-5p GCGGUGAUGCCGAUGGUGCGAG gga miR-133b UUGGUCCCCUUCAACCAGCUA mo-miR 652 AAUGGCGCCACUAGGGUUGUG gga-miR-133c UUGGUCCCCUUCAACCAGCUGC rno-miR-664 UAUUCAUUUACUCCCCAGCCUA gga-miR-135a UAUGGCUUUUUAUUCCUAUGUGA mo-miR-671 UCCGGUUCUCAGGGCUCCACC gga-miR-137 UAUUGCUUAAGAAUACGCGUAG mo-πuR-672 UGAGGUUGGUGUACUGUGUGUGA gga-miR-138 AGCUGGUGUUGUGAAUC mo-miR-673 CUCACAGCUCCGGUCCUUGGAG gga-miR-140 AGUGGUUUUACCCUAUGGUAG mo-miR-674-3p CACAGCUCCCAUCUCAGAACAA gga-miR-140* CCACAGGGUAGAACCACGGAC rno-miR-674-5p GCACUGAGAUGGGAGUGGUGUA gga-miR-142-3p UGUAGUGUUUCCUACUUUAUGG mo-miR-708 AAGGAGCUUACAAUCUAGCUGGG gga miR 142-5p CCCAUAAAGUAGAAAGCACUAC mo miR 708* CAACUAGACUGUGAGCUUCUAG gga-πuR-144 CUACAGUAUAGAUGAUGUACUC mo miR-742 GAAAGCCACCAUGUUGGGUAAA gga-miR-146a UGAGAACUGAAUUCCAUGGGUU mo-miR-743a GAAAGACGCCAAACUGGGUAGA gga miR-146b UGAGAACUGAAUUCCAUAGGCG mo-miR-743b GAAAGACACCAUACUGAAUAGA gga miR-146b* CCCUAUGGAUUCAGUUCUGC rno-miR-758 UUUGUGACCUGGUCCACUAACC gga-miR-147 GUGUGCGGAAAUGCUUCUGC rπo-miR-760-3p CGGCUCUGGGUCUGUGGGGA gga-miR-148a UCAGUGCACUACAGAACUUϋOU mo-miR-760-5p CCCCUCAGGCCACCAGAGCCCG gga-miR-153 UUGCAUAQUCACAAAAGUGA mo miR 770 AGCACCACGUGUCUGGGCCACG gga-miR-155 UUAAUGCUAAUCGUGAUAGGGG mo-miR-7a UGGAAGACUAGUGAUUUUGUUGU gga-miR-15a UAGCAGCACAUAAUGGUUUGU mo-miR-7a* ACAACAAAUCACAGUCUGCCAU gga-miR-15b UAGCAGCACAUCAUGGUUUGCA mo-miR 7b UGGAAGACUUGUGAUUUUGUUGU gga miR 16 UAGCAGCACGUAAAUAUUGGUG mo miR 871 UAUUCAGAUUGGUGCCGGUCACA gga-miR-17-3p ACUGCAGUGAAGGCACUUGU mo miR-872 AAGGUUACUUGUUAGUUCAGG gga-miR-17-5p CAAAGUGCUUACAGUGCAGGUAGU mo miR-872* UGAACUAUUGCAGUAGCCUCCU gga-miR- 181a AAC AUUCAACGCUGUCGGUG AGU rno-miR 873 GCAGGAACUUGUGAGUCUCCU gga-miR-lSla* ACCAUCGACCGUUGAUUGUACC mo-miR-874 CUGCCCUGGCCCGAGGGACCGA gga-miR-181b AACAUUCAUUGCUGUCGGUGGG mo-miR-877 GUAGAGGAGAUGGCGCAGGG gga-miR-183 UAUGGCACUGGUAGAAUUCACUG mo-miR-878 GCAUGACACCAUACUGGGUAGA gga miR 184 UGGACGGAGAACUGAUAAGGGU mo-miR-879 AGAGGCUUAUAGCUCUAAGCC gga-πuR-187 UCGUGUCUUGUGUUGCAGCC mo-miR-880 UACUCCAUUCAUUCUGAGUAGA gga-miR-18a UAAGGUGCAUCUAGUGCAGAUA mo-miR-881 AACUGUGGCAUUUCUGAAUAGA gga-miR-18b UAAGGUGCAUCUAGUGCAGUUA rno-tniR-883 UAACUGCAACAUCUCUCAGUAU gga-miR-190 UGAUAUGUUUGAUAUAUUAGGU mo miR 9 UCUUUGGUUAUCUAGCUGUAUGA gga-raiR-193b AACUGGCCCACAAAGUCCCGCUUU rno-miR-9* AUAAAGCUAGAUAACCGAAAGU gga-miR-194 UGUAACAGCAACUCCAUGUGGA mo-trnR-92a UAUUGCACUUGUCCCGGCCUG gga miR-196 UAGGUAGUUUCAUGUUGUUGG mo-miR-92b UAUUGCACUCGUCCCGGCCUCC gga miR-199 CCCAGUGUUCAGACUACCUGUUC mo-miR-93 CAAAGUGCUGUUCGUGCAGGUAG gga-miR-199* UACAGUAGUCUGCACAUUGG mo-miR-96 UUUGGCACUAGCACAUUUUUGCU gga-miR 19a UGUGCAAAUCUAUGCAAAACUGA mo-miR-98 UGAGGUAGUAAGUUGUAUUGUU gga miR-19b UGUGCAAAUCCAUGCAAAACUGA mo-miR 99a AACCCGUAGAUCCGAUCUUGUG gga miR-la UGGAAUGUAAAGAAGUAUGUA mo πuR-99a* CAAGCUCGUUUCUAUGGGUCUG gga miR-lb UGGAAUGUUAAGAAGUAUGUA mo-miR-99b CACCCGUAGAACCGACCUUGCG gga miR-200a UAACACUGUCUGGUAACGAUGU mo-miR-99b* CAAGCUCGUGUCUGUGGGUCCG gga-miR-200b UAAUACUGCCUGGUAAUGAUGAU rτv-miR-rRl-1 CGAUCGCACCUUUGGCCGGCCGG gga-miR 202 AGAGGCAUAGAGCAUGGGAAAA rrv-miR-rRl-1* GGCCACCGAGGAUGCGGUC gga-miR-202* UUUCCUAUGCAUAUACUUCUUU πv-miR-rRl-2 AUACGGCGCUGCACGGUUGGA gga-imR-203 GUGAAAUGUUUAGGACCACUUG rrv-miR-rRl-3 CCCGAUGAGCAGUUAGUCC gga-miR-204 UUCCCUUUGUCAUCCUAUGCCU rrv-miR rRl-4 UGGGGAGGGCGGUCAGCGCGCG gga-miR-205a UCCUUCAUUCCACCGGAGUCUG rrv-miR-rRl-4* CUCGUUAACCGCCCUCCCGAGA gga-miR-205b CCCUUCAUUCCACCGGAAUCUG rrv-miR-rRl-5 CCGGAACCCAAAGACACGUGCCCG gga-miR-206 UGGAAUGUAAGGAAGUGUGUGG rτv-miR rRI 6 CGCGGAAAGGUGUGCACAUCGUA gga-miR-20a UAAAGUGCUUAUAGUGCAGGUAG rrv-miR rRl 6* CGAUGUACGCCCUUUCGCAGU gga-miR 20b CAAAGUGCUCAUAGUGCAGGUAG iτv-miR-rRl-7-3p CGCACGUCGAUUGCUCUCUAG gga-miR-21 UAGCUUAUC AGACUG AUGUTJGA rrv-miR rRl-7-5p UGGAGAGCAGUUAACGUGCGUUC gga-miR-211 UUCCCUUUGUCAUCCUAUGCCU sla miR-100 AACCCGUAGAUCCGAACUUGUG gga-miR-215 AUGACCUAUGAAUUGACAGAC sla miR-101 UACAGUACUGUGAUAACUGAAG gga-miR-216 UAAUCUCAGCUGGCAACUGUG sla-πuR-105 UCAAAUGCUCAGACUCCUGU gga-πuR-217 UACUGCAUCAGGAACUGAUUGGAU sla-miR-106a AAAAGUGCUUACAGUGCAGGUAGC gga-miR-218 UUGUGCUUGAUCUAACCAUGU sla-miR-106b UAAAGUGCUGACAGUGCAGAU gga-πuR-219 UGAUUGUCCAAACGCAAUUCU sla-miR-10a UACCCUGUAGAUCCGAAUUUGUG gga-πuR 221 AGCUACAUUGUCUGCUGGGUUUC sla-miR-125b UCCCUGAGACCCUAACUUGUGA gga-miR-222 AGCUACAUCUGGCUACUGGGUCUC sla-miR-127 UCGGAUCCGUCUGAGCUUGGCU gga-miR-223 UGUCAGUUUGUCAAAUACCCC sla-miR-128 UCACAGUGAACCGGUCUCUUUU gga-miR-23b AUCACAUUGCCAGGGAUUACC sla-miR 133a UUGGUCCCCUUCAACCAGCUGU gga-miR-24 UGGCUCAGUUCAGCAGGAACAG sla-miR-147 GUGUGUGGAAAUGCUUCUGC gga-miR-26a UUCAAGUAAUCCAGGAUAGGC sla-miR-15a UAGCAGCACAUAAUGGUUUGUG gga-miR-27b UUCACAGUGGCUAAGUUCUGC sla-miR-16 UAGCAGCACGUAAAUAUUGGCG gga-miR-29a UAGCACCAUUUGAAAUCGGUU sla-miR-17-3p ACUGCAGUGAAGGCACUUGU gga miR 29b UAGCACCAUUUGAAAUCAGUGUU sla-miR-17-5p CAAAGUGCUUACAGUGCAGGUAGU gga-miR-29c UAGCACCAUUUGAAAUCGGU sla-miR-18 UAAGGUGCAUCUAGUGCAGAUA gga-miR-301 C AGUGC AAU AAU AUUGUC AAAGCAU sla-miR-18 Ia AACAUUCAACGCUGUCGGUGAGU gga-miR-302a AAGUGCUUCCAUGUUUUAGUGA sla miR 183 UAUGGCACUGGUAGAAUUCACUG gga-miR-302b UAAGUGCUUCCAUGUUUUAGUAG sla-miR-198 GGUCCAGAGGGGAGCUCGA gga-miR-302b* ACUUUAACAUGGAGGUGCUUUCU sla-miR-199a CCCAGUGUUCAGACUACCUGUUC gga-miR 302c UAAGUGCUUCCAUGUUUCAGUGG sla-miR-19a UGUGCAAAUCUAUGCAAAACUGA gga miR 302c* UUUAACAUGGAGGUACCUGCUG sla-miR-19b UGUGCAAAUCCAUGCAAAACUGA gga miR 302d UAAGUGCUUCCAUGUUUUAGUUG sla-miR-20 UAAAGUGCUUAUAGUGCAGGUA gga miR-30a 3p CUUUCAGUCGGAUGUUUGCAGC sla-miR-204 UUCCCUUUGUCAUCCUAUGCCU gga miR 30a-5p UGUAAACAUCCUCGACUGGAAG sla-miR-214 ACAGCAGGCACAGACAGGCAG gga miR-30b UGUAAACAUCCUACACUCAGCU sla miR-218 UUGUGCUUGAUCUAACCAUGU gga-miR-30c UGUAAACAUCCUACACUCUCAGCU sla-miR-22 AAGCUGCCAGUUGAAGAACUGU gga-miR-30d UGUAAACAUCCCCGACUGGAAG sla-miR-223 UGUCAGUUUGUCAAAUACCCC gga-miR-30e UGUAAACAUCCUUGACUGG sla-miR-23a AUCACAUUGCCAGGGAUUUCC gga-miR-31 AGGCAAGAUGUUGGCAUAGCUG sla-miR-27a UUCACAGUGGCUAAGUUCCGCC gga miR 32 UAUUGCACAUUACUAAGUUGC sla-miR-28 AAGGAGCUCACAGUCUAUUGAG gga-miR-33 GUGCAUUGUAGUUGCAUUG sla-miR-29a CUAGCACCAUCUGAAAUCGGUU gga-miR-34a UGGCAGUGUCUUAGCUGGUUOUU sla imR 29b UAGCACCAUUUGAAAUCAGU gga-miR-34b CAGGCAGUGUAGUUAGCUGAUUG sla-miR 32 UAUUGCACAUUACUAAGUUGC gga-miR-34c AGGCAGUGUAGUUAGCUGAUUGC sla-imR-34a UGGCAGUGUCUUAGCUGGUUGU gga-miR-365 UAAUGCCCCUAAAAAUCCUUAU sla miR-7 UGGAAGACUAGUGAUUUUGUU gga-miR-367 AAUUGCACUUUAGCAAUGGUG sla-miR-92 UAUUGCACUUGUCCCGGCCUGU gga-miR-375 UUUGUUCGUUCGGCUCGCGUUA sla-miR-93 AAAGUGCUGUUCGUGCAGGUAG gga miR-383 AGAUCAGAAGGUGAUUGUGGCU sla-miR-95 UUCAACGGGUAUUUAUUGAGCA gga-miR-429 UAAUACUGUCUGGUAAUGCCGU sla-miR-96 UUUGGCACUAGCACAUUUUUGC gga miR-449 UGGCAGUGUAUGUUAGCUGGU sme-bantam-a UGAGAUCACUAUGAAAGCUGG gga-miR-451 AAACCGUUACCAUUACUGAGUUU sme-bantam-b UGAGAUCACUGCGAAAGCUGAU gga-miR-455 UAUGUGCCCUUGGACUACAUCG sme-bantam c UGAGAUCAUUAUGAAAGCUUUU gga-miR-456 CAGGCUGGUUAGAUGGUUGUCA sme-let-7a UGAGGUAGAAUGUUGGAUGACU gga-raiR-460 CCUGCAUUGUACACACUGUGUG sme-let-7b UGAGGUAGAUUGUUGGAUGACU gga miR-466 AUAUAUACACACACACAUAAGAC sme-lBt-7b* CCAUUCAACUAUCUGUCUUCUC gga miR-489 AGUGACAUCAUAUGUACGGCUGC sme-let-7c UGAGGUAGUGACUCAAAAGGUU gga miR-490 CAACCUGGAGGACUCCAUGCUG sme-lin-4 UCCCUGAGACCUUCGACUGUGU gga-miR-499 UUAAGACUUGUAGUGAUGUUUAG sme-miR-10 AACCCUGUAGAUCCGAGUUUGA gga-miR-7 UGGAAGACUAGUGAUUUUGUUG sme-miR-10* UCGAAUCUUCAAGGUGAA gga-miR-757 GCAGAGCUGCAGAUGGGAUUC ame-miR-12 UG AGU AUUCU AUCAGGAGUCGA gga-miR-7b UGGAAGACUAGUGAUUUUUGUU sme-πuR-124a UAAGGCACGCGGUGAAUGCUU gga-miR-9 UCUUUGGUUAUCUAGCUGUAUGA sme-miR-124b UAAGGCACGCGGUGAAUGCUGA gga-miR-9* UAAAGCUAGAGAACCGAAUGU sme-miR 124o UAAGGCACGCGGUGAAUGCCA gga-miR 92 UAUUGCACUUGUCCCGGCCUG sme-miR 124o* GCGCUCACCUCGUGACCUUUGU gga-miR-99a AACCCGUAGAUCCGAUCUUGUG sme miR-125a UCCCUGAGACCAUUGACUGCAU ggo-miR-100 AACCCGUAGAUCCGAACUUGUG sme-miR-125a* GUAGUUUUUGGUAUCAGGAU ggo-miR-101 UACAGUACUGUGAUAACUGAAG sme-miR-125b UCCCUGAGAUCAUAAUAUGCCU ggo-miR-103 AGCAGCAUUGUACAGGGCUAUGA εme miR-13 UAUCACAGUCAUGCUAAAGAGC ggo-miR-105 UCAAAUGCUCAGACUCCUGU sme-miR-133 UUGGUCCCCAUCAACCAGCA ggo-raiR-106a AAAAGUGCUUACAGUGCAGGUAGC sme-miR-184 GACGGAGGUUUGCUAAGGAA ggo-miR-106b UAAAGUGCUGACAGUGCAGAU sme-miR-190a AGAUAUGUUUGGUUAAUUGGUGA ggo-miR-107 AGCAGCAUUGUACAGGGCUAUCA sme-miR-190a* ACCACUGACCGAGCAU AUCCA ggo miR-lOa UACCCUGUAGAUCCGAAUUUGUG sme-miR-190b UGAUAUGUUUGGUUUAUUGGUGA ggo-miR-10b UACCCUGUAGAACCGAAUUUGU sme-πuR-190b* ACCAUUAGCCUAAUGUAUCGUGU ggo-miR-124a UUAAGGCACGCGGUGAAUGCCA sme miR Ia UGGAAUGUCGAGAAAUAUGCAU ggo-miR-125b UCCCUGAGACCCUAACUUGUGA sme-miR-lb UGGAAUGUCGUGAAUUAUGGUC ggo-miR-130a CAGUGCAAUGUUAAAAGGGC sme-miR-lc UGGAAUGUUGUGAAUAGUGUC ggo-miR-133a UUGGUCCCCUUCAACCAGCUGU sme-nuR-219 UGAUUGUCCAUACGCAGUUCUCA ggo-πuR-134 UGUGACUGGUUGACCAGAGGG sme-πuR-277a UAAAUGCACUAUCGGAUAUGAC ggo nuR 135 UAUGGCUUUUUAUUCCUAUGUGA sme-miR-277b AAAAUGCAUUAUCUGGCCAAGA ggo miR-136 ACUCCAUUUGUUUUGAUGAUGGA sme-miR-277b* UUGAUCAGAAAUGCAGCUUC ggo-miR-141 AACACUGUCUGGUAAAGAUGG sme-miR-277c UAAAUGCAUUAUCUGGUAUGAU ggo miR-143 UGAGAUGAAGCACUGUAGCUCA sme-miR-277d UAAAUGCAUUUAUCUGGCCAAG ggo-miR-145 GUCCAGUUUUCCCAGGAAUCCCUU sme-miR-278 UCGGUGGGAGUAACAUUCGA ggo-πuR-153 UUGCAUAGUCACAAAAGUGA sme-miR-281 UGUC AUGGAU AUGCUCUUC ggo-mιR-154 UAGGUUAUCCGUGUUGCCUUCG sme-miR-281* UGAAG AGCU AUUCAUGAGGU ggo-miR 15a UAGCAGCACAUAAUGGUUUGUG sme-miR-2a UAUCACAGCCCCGCUUGGAACGCU ggo nuR 15b UAGCAGCACAUCAUGGUUUACA sme-miR-2a* GUUCUACGGUGUUGUGAUAU ggo-πuR 16 UAGCAGCACGUAAAUAUUGGCG sme-miR-2b UCACAGCCAAUUUUGAUGAGAU ggo miR-17-3p ACUGCAGUGAAGGCACUUGU sme miR-2b* UCAUCAUUGUUGGUUGUCAG ggo miR-17-5p CAAAGUGCUUACAGUGCAGGUAGU sme-miR-2o UCACAGCCAAAACUGAUGAUCU ggo-miR-18 UAAGGUGCAUCUAGUGCAGAUA sme miR-2d UCACAGCCAAAUUUGAUGUCC ggo-miR-181a AACAUUCAACGCUGUCGGUGAGU sme miR 3 Ia AGGCAAGAUGUUGGCAUAACUGA ggo-miR-181a* ACCAUCGACCGUUGAUUGUACC sme miR 3 Ib AGGCAAGAUGCUGGCAUAGCUGA ggo-miR-181b AACAUUCAUUGCUGUCGGUGGGUU sme miR 36 UCACCGGGUAGACAUUCAUUA ggo-miR-181c AACAUUCAACCUGUCGGUGAGU sme imR-36* UGAUGCAUGCUACUUGGUUU ggo miR-183 UAUGGCACUGGUAGAAUUCACUG sme-miR 61 UGACUAGAAAGUUCACUUACUGU ggo-miR-186 CAAAGAAUUCUCCUUUUGGGCUU sme-miR 67 UCACAACCUCCAUGAACGAGGGU ggo-miR-187 UCGUGUCUUGUGUUGCAGCCG sme miR-71a UGAAAGACACGGGUAGUGAGAU ggo-miR-190 UGAUAUGUUUGAUAUAUUAGGU sme-miR-71b UGAAAGACACAGGUAGUGGGAC ggo-miR-194 UGUAACAGCAACUCCAUGUGGA sme-miR-71b* UCCUUCUAAUGUGUUUUUCG ggo-miR-195 UAGCAGCACAGAAAUAUUGGC sme-miR-71c UGAAAGACAUGGGUAGUGAGAU ggo-miR-196 UAGGUAGUUUCAUGUUGUUGG sme-πuR-745 UGCUGCCUGGUUAAGAGCUGUGU ggo-miR 198 GGUCCAGAGGGGAGAUAGG sme-miR-746 UAGCACCAGGGUAUAUCGGGAU ggo-miR-199a CCCAGUGUUCAGACUACCUGUUC sme-miR-747 UAAUCUCAUCUGGUAAUUGAAGU ggo-miR-19a UGUGCAAAUCUAUGCAAAACUGA sme-miR 748 UGGACGGAAGUGUAAUGAG ggomiR-19b UGUGCAAAUCCAUGCAAAACUGA sme-miR-749 GCUGGGAUGAGCCUCGGUGGU ggo-miR-20 UAAAGUGCUUAUAGUGCAGGUA sme-miR-750 UCAGAUCUAACUCUUCCAGUUCU ggo-miR-200c AAUACUGCCGGGUAAUGAUGGA sme-miR-751 CAUGUUUGAAUGGCCAUOACA ggo-miR-204 UUCCCUUUGUCAUCCUAUGCCU sme-imR-752 AGUCAGCAUUGGUGGUUU ggo-miR-205 UCCUUCAUUCCACCGGAGUCUG sme-miR-753 GAGCUUGGAUUGUGAUCUCA ggo miR-21 UAGCUUAUCAGACUGAUGUUGA sme-miR-754 GUUGCUUGGGGUUAUUACUA ggo-miR-214 ACAGCAGGCACAGACAGGCAG sme-miR-755 UGGAGCUAUUGUAUUUCACC ggo-miR-215 AUGACCUAUGAAUUGACAGAC sme-miR-756 CGAUAUGUGGUAAUUUGGAUGA ggo-miR-216 UAAUCUCAGCUGGCAACUGUG sme-miR-79 GUAAAGCUAAAUUACCAAAGUGC ggo-miR-217 UACUGCAUCAGGAACUGAUUGGAU sme-miR-7a UGGAAGACUAUUGAUUUAGUUGA ggo-miR-218 UUGUGCUUGAUCUAACCAUGU sme-miR-7b UGGAAGACUGUCGAUUUCGUUGU ggo-miR-219 UGAUUGUCCAAACGCAAUUCU srae-miR-7o UGGAAGACUGAUGAUUUGCUGA ggo-miR-220 CCACACCGUGUCUGACACUUU sme-πnR-8 UAAUACUGUCAGGUAACGAUGCC ggo miR-221 AGCUACAUUGUCUGCUGGGUUUC sme-miR-87a UGAGCAAAGUUUCAAGUGUA ggo-miR-223 UGUCAGUUUGUCAAAUACCCC sme-miR-87b GUGAGCAAAGCUUCAAAUGAG ggo-raiR-224 CAAGUCACUAGUGGUUCCGUUUA sme-miR 92 GAUUGCACUAGUUAAUUAUC ggo miR 23a AUCACAUUGCCAGGGAUUUCC ssc-let-7c UGAGGUAGUAGGUUGUAUGGUU ggo miR 24 UGGCUCAGUUCAGCAGGAACAG ssc-let-7f UGAGGUAGUAGAUUGUAUAGUU ggo mιR-25 CAUUGCACUUGUCUCGGUCUGA ssc-let-7i UGAGGUAGUAGUUUGUGCU ggo-miR-26a UUCAAGUAAUCCAGGAUAGGCU ssc-miR-103 AGCAGCAUUGUACAGGGCUAUGA ggo-miR-27a UUCACAGUGGCUAAGUUCCGCC ssc-miR-105-I UCAAAUGCUCAGACUCCUGU ggo-miR-28 AAGGAGCUCACAGUCUAUUGAG ssc-miR-I05-2 UCAAAUGCUCAGACUCCUUG ggo-miR-29a CUAGCACCAUCUGAAAUCGGUU ssomiR-106a AAAAGUGCUUACAGUGCAGGUAGC ggo-miR-29b UAGCACCAUUUGAAAUCAGU ssc-miR-107 AGCAGCAUUGUACAGGGCUAUCA ggo-miR-30a-3p CUUUCAGUCGGAUGUUUGCAGC ssc-miR-122 UGGAGUGUGACAAUGGUGUUUGU ggo-miR-30a-5p UGUAAACAUCCUCGACUGGAAG ssc-miR-124a UUAAGGCACGCGGUGAAUGCCA ggo-miR-30b UGUAAACAUCCUACACUCAGC ssc-miR-125b UCCCUGAGACCCUAACUUGUGA ggo-miR-30d UGUAAACAUCCCCGACUGGAAG ssc-miR-128 UCACAGUGAACCGGUCUCUUUU ggo-πuR-31 GGCAAGAUGCUGGCAUAGCUG SSC-mlR-135 UAUGGCUUUUUAUUCCUAUGUGA ggo-miR-32 UAUUGCACAUUAOUAAGUUGC ssomiR-136 ACUCCAUUUGUUUUGAUGAUGGA ggo-raiR-33 GUGCAUUGUAGUUGCAUUG ssc-miR-139 UCUACAGUGCACGUGUCU ggo-miR-34a UGGCAGUGUCUUAGCUGGUUGU ssc-miR-140 AGUGGUUUUACCCUAUGGUAG ggo-miR-7 UGGAAGACUAGUGAUUUUGUU ssc-raiR-145 GUCCAGUUUUCCCAGGAA.UCCCUU ggo-miR-9 UCUUUGGUUAUCUAGCUGUAUGA ssc-miR-148a UCAGUGCACUACAGAACUUUGU ggo-raiR-92 UAUUGCACUUGUCCCGGCCUGU ssc-miR-153 UUGCAUAGUCACAAAAGUGA ggo-miR-93 AAAGUGCUGUUCGUGCAGGUAG ssc-miR-15b CCGCAGCACAUCAUGGUUUACA ggo-miR-95 UUCAACGGGUAUUUAUUGAGCA ssc-raiR-18 UAAGGUGCAUCUAGUGCAGAUA ggo-miR-96 UUUGGCACUAGCACAUUUUUGC ssc-miR-181b AACAUUCAUUGCUGUCGGUGGGUU gEO-miR-98 UGAGGUAGUAAOUUGUAUUGUU ssc-miR-lβlo AACAUUCAACCUGUCGGUC3AGU ggo-miR-99a AACCCGUAGAUCCGAUCUUGUG sso-miR-183 U AUGGC ACUGGUAG AAUUCACUG hcmv-miR-UL112 AAGUGACGGUGAGAUCCAGGCU ssc-miR-184 UGGACGGAG AACUGAU AAGGGU hcmv-miR-UL148D UCGUCCUCCCCUUCUUCACCG ssc-miR-186 CAAAGAAUUCUCCUUUUGGGCUU hcrav-miR-UL22A UAACUAGCCUUCCCGUGAGA ssomiR-196 UAGGUAGUUUCAUGUUGUUGG hcmv-miR-UL22A* UCACCAGAAUGCUAGUUUGUAG aso-miR-19a UGUGCAAAUCUAUGCAAAACUGA hcrav-miR-UL36 UCGUUGAAGACACCUGGAAAGA sso-miR-20 UAAAGUGCUUAUAGUGCAGGUA hcmv-miR-UL36* UUUCCAGGUGUUUUCAACGUGC ssc-miR-204 UUCCCUUUGUCAUCCUAUGCCU hcmv-miR-UL70-3p GGGGAUGGGCUGGCGCGCGG ssc-miR-205 UCCUUCAUUCCACCGGAGUCUG hcmv-miR-UL70-5p UGCGUCUCGGCCUCGUCCAGA ssc-miR-21 UAGCUUAUCAGACUGAUGUUGA hcmv-miR-US25-l AACCGCUCAGUGGCUCGGACC ssc-miR-214 ACAGCAGGCACAGACAGGCAG hcmv-miR-US25-l* UCCGAACGCUAGGUCGGUUCUC ssc-miR-216 UAAUCUC AGCUGGC AACUGUG homv-miR-US25-2-3p AUCCACUUGGAGAGCUCCCGCGG ssc-miR-217 UACUGCAUCAGGAACUGAUUGGAU hcmv-miR-US25-2-5p AGCGGUCUGUUCAGGUGGAUGA ssc-miR-224 CAAGUCACUAGUGGUUCCGUUUA hcmv-miR-US33-3p UCACGGUCCGAGCACAUCCA ssc-miR-23a AUCAC AUUGCCAGGGAUUUCC hcmv-miR-US33-5p GAUUGUGCCCGGACCGUGGGCG ssc-miR-24 UGGCUCAGUUCAGCAGGAACAG homv-miR-US4 CGACAUGGACGUGCAGGGGGAU ssc-miR-26a UUCAAGUAAUCCAGGAUAGGCU hcmv-πuR-US5-l UGACAAGCCUGACGAGAGCGU ssc-miR-27a UUCACAGUGGCUAAGUUCCGC hcmv-miR-US5-2 UUAUGAUAGGUGUGACGAUGUC ssc-miR-28 AAGGAGCUCACACUCUAUUGAG hivl-miR-Hl CCAGGGAGGCGUGCCUGGGC sso-miR-29b UAGCACCAUUUGAAAUCAGU hivl-miR-N367 ACUGACCUUUGGAUGGUGCUUCAA sso-miR-29c UAGCACCAUUUGAAAUCGGUUA hivl-miRwTAR-3p UCUCUGGCUAACUAGGGAACCCA SSO-miR-301 CAGUCCAAUAQUAUUGUCAAAGC hivl-miR-TAR-5p UCUCUCUGGUUAGACCAGAUCUGA ssc-miR-30c UGUAAACAUCCUACACUCUCAGC hsvl-miR-Hl UGGAAGGACGGGAAGUGGAAG sso-miR-32 UAUUGCACAUUACUAAGUUGC kshv-miR-K12-l AUUACAGGAAACUGGGUGUAAGC sso-miR-323 GCACAUUACACGGUCGACCUCU kshv-miR K12-10a UAGUGUUGUCCCCCCGAGUGGC ssc-miR-325 CCUAGUAGGUGUUCAGUAAGUGU kshv-πuR-K12-10b UGGUGUUGUCCCCCCGAGUGGC ssc-miR-326 CCUCUGGGCCCUUCCUCCAG kshv-miR-K12-ll UUAAUGCUUAGCCUGUGUCCGA ssc-miR-7 UGGAAGACUAGUGAUUUUGUU kshv-πuR-K12-12 ACCAGGCCACCAUUCCUCUCCG ssc-miR-9-1 UCUUUGGUUAUCUAGCUGUAUGA kshv-πuR-KI2-2 AACUGUAGUCCGGGUCGAUCUG ssc-miR-9-2 UCUUUGGUUAUCUAGCUGUAUGA kshv-miR-KI2-3 UCACAUUCUGAGGACGGCAGCGA ssc-miR-95 UUCAACGGGUAUUUAUUGAGCA kshv-miR-K12-3* UCGCGGUCACAGAAUGUGACA ssc-miR-99b CACCCGUAGAACCGACCUUGCG kshv-miR-K12-4-3p UAGAAUACUOAGGCCUAGCUGA ssy-miR 506 UAAGGCACCCUUCUGAGUAGA kshv-miR-K.12-4-5p AGCUAAACCGCAGUACUCUAGG ssy-miR-507 UUUUGCACCUUUUGGAGUGAA kshv-imR-K.12-5 UAGGAUGCCUGGAACUUGCCGG ssy-miR-508 UGAUUGUAGCCCUUUUGAGUAGA kshv-miR-K12-6-3p UGAUGGUUUUCGGGCUGUUGAG ssy-rmR-509a UGAUUGGUACGUCUGUGGGUAGA kshv-miR-K12-6-5p CCAGCAGCACCUAAUCCAUCGG ssy-tniR-509b UGAUUGGUACGUCUGUAGGUAGA kshv-miR-K12-7 UGAUCCCAUGUUGCUGGCGCU ssy-miR-510 UACUCCGGAGAGUGGCAAUCACA kshv-miR-K12-8 UAGGCGCGACUGAGAGAGCACG ssy-miR-513a UUCACAGGGAGGUGUCAUUUAU kshv-miR-K12-9 CUGGGUAUACGCAGCUGCGUAA ssy-miR-513b UUCACAAGGAGGUGUCAUUUAU kshv-miR-K.12-9* ACCCAOCUGCGUAAACCCCGCU ssy-πύR-513o UUCCCAAGGAGGUGUCAUUUAC lca-miR-125b UCCCUGAGACCCUAACUUGUGA ssy miR-514 AUUGACACUUCUGUGAGUAG lca-miR-15a UAGCAGCACAUAAUGGUUUGUG sv40-miR-S 1 -3p GCCUGUUUCAUGCCCUGAGU lca-miR-16 UAGCAGCACGUAAAUAUUGGUG sv40-rmR-Sl-5p UGAGGGGCCUGAAAUGAGCCUU lca-miR-17-3p ACUGCAGUGAAGGCACUUGU xla-miR-133a UUGGUCCCCUUCAACCAGCUGU lca-miR-17-5p CAAAGUGCUUACAGUGCAGGUAGU xla-miR-18 UAAGGUGCAUCUAGUGCAGUUAG lca-miR-18 UAAGGUGCAUCUAGUGCAGAUA xIa-miR-19b UGUGCAAAUCC AUGC AAAACUG A lca-miR-19a UGUGCAAAUCUAUGCAAAACUGA xla-miR-20 CAAAGUGCUCAUAGUGCAGGUAG lca-miR-19b UGUGCAAAUCCAUOCAAAACUGA xla-nuR-427 AAAGUGCUUUCUGUUUUGGGCG lca-miR-20 UAAAGUGCUUAUAGUGCAGGUA xla-nuR-428 UAAGUGCUCUCUAGUUCGGUUG lca-miR-216 UAAUCUCAGCUGGCAACUGUG xIa-miR-429 UAAUACUGUCUGGUAAUGCCG lca-miR-218 UUGUGCUUGAUCUAACCAUGU xtr-let-7a UGAGGUAGUAGGUUGUAUAGUU lea miR-22 AAGCUGCCAGUUGAAGAACUGU xtr-let-7b UGAGGUAGUAGUUUGUOUAGUU lca-miR-23a AUCACAUUGCCAGGGAUUUCC xtr-let-7c UGAGGUAGUAOGUUGUAUGGUU lca-miR-27a UUCACAGUGGCUAAGUUCCGCC xtr-let-7c UGAGGUAGUAGGUUGUUUAGUU loa-miR-92 UAUUGCACUUGUCCCGGCCUGU xtr-let-7f UGAGGUAGUAGAUUGUAUAGUU lla-miR-100 AACCCGUAGAUCCGAACUUGUG xtr-let-7g UGAGGUAGUUGUUUGUACAGU

IIa-miR-101 UACAGUACUGUGAUAACUGAAG xtr-let-7i UGAGGUAGUAGUUUGUGCUGU Ha-miR-103 AGCAGCAUUGUACAGGGCUAUGA xtr-miR-100 AACCCGUAGAUCCGAACUUGUG lla-miR-105 UCAAAUGCUCAGACUCCUGU xtr-miR-lOla UACAGUACUGUGAUAACUGAAG lla-miR-106b UAAAGUGCUGACAGUGCAGAU xtr-miR-103 AGCAGCAUUGUACAGGGCUAUGA

Ua-miR-l^Q7 AGCAGCAUUGUACAGGGCUAUCA xtr-miR-106 AAAAGUGCUUAUAGUGCAGGUAGA

Ua miR-124a UUAAGGCACGCGGUGAAUGCCA xtr-miR-107 AGCAGCAUUGUACAGGGCUAUCA

Ua-miR-125b UCCCUGAGACCCUAACUUGUGA xtr-miR-lOa UACCCUGUAGAUCCGAAUUUGUG

Ua-miR-127 UCGGAUCCGUCUGAGCUUGGCU xtr-miR-10b UACCCUGUAGAACCGAAUUUGU

Ua-miR-133a UUGGUCCCCUUCAACCAGCUGU xtr-miR-lOo CACCCUGUAGAAUCGAAUUUGU

Ha-miR-135 UAUGGCUUUUUAUUCCUAUGUGA xtr-miR-122 UGGAGUGUGACAAUGGUGUUUGU lla-miR-139 UCUACAGUGCACGUGUCU xtr-miR-124 UUAAGGCACGCGGUGAAUGCCA

Ha-miR-143 UGAGAUGAAGCACUGUAGCUCA xtr-miR-125a UCCCUGAGACCCUUAACCUGUG lla-miR-lSa UAGCAGCACAUAAUGGUUUGUG xtr-miR-12Sb UCCCUGAGACCCUAACUUGUGA lla-miR-lSb UAGCAGCACAUCAUGGUUUACA xtr-miR-126 UCGUACCGUGAGUAAUAAUGC lla-miR-16 UAGCAGCACGUAAAUAUUGGCG xtr-miR-126* CAUUAUUACUUUUGGUACGCG lla-miR-17-3p ACUGCAGUGAAGGCACUUGU xtr miR 128 UCACAGUGAACCGGUCUCUUUU lla-miR-17 5p CAAAGUGCUUACAGUGCAGGUAGU xtr-miR-129 CUUUUUGCGGUCUGGGCUUGC

Ha-miR-18 UAAGGUGCAUCUAGUGCAGAUA xli-miR-130a CAGUGCAAUGUUAAAAGGGCAU

Ila miR 181a AACAUUCAACGCUGUCGGUGAGU xtr-miR-130b CAGUGCAAUGAUGAAAGGGCAU

Ua miR-181a* ACCAUCGACCGUUGAUUGUACC xtr-miR-130c CAGUGCAAUAUUAAAAGGGCAU

11a miR 181b AACAUUCAUUGCUGUCGGUGGGUU xtr miR 132 UAACAGUCUACAGCCAUGGUCG lla miR-196 UAGGUAGUUUCAUGUUGUUGGG xtr-miR-133a UUGGUCCCCUUCAACCAGCUGU

Ua-miR-198 GGUCCAGAAGGGAGCUAGG xtr-miR-133b UUGGUCCCCUUCAACCAGCUA lla-miR-199a CCCAGUGUUCAGACUACCUGUUC xtr-miR-133c UUGGUCCCCUUCAACCAGCUGC lla-miR-19a UGUGCAAAUCUAUGCAAAACUGA xtr-πuR-133d UUGGUCCCCUUCAACCAGCCGC lla-miR-19b UGUGCAAAUCCAUGCAAAACUGA xtr-miR-135 UAUGGCUUUUUAUUCCUAUGUGA lla-miR-20 UAAAGUGCUUAUAGUGCAGGUA xtr-miR-137 UAUUGCUUAAGAAUACGCGUAG lla-miR-205 UCCUUCAUUCCACCGGAGUCUG xtr miR 138 AGCUGGUGUUGUGAAUC lla-miR-218 UUGUGCUUGAUCUAACCAUGU xtr-miR-139 UCUACAGUGCAUGUGUCU

Ila-miR-22 AAGCUGCCAGUUGAAGAACUGU xtr-miR-140 AGUGGUUUUACCCUAUGGUAG lla-miR-25 CAUUGCACUUGUCUCGGUCUGA xtr-miR-142-3p UGUAGUGUUUCCUACUUUAUGGA lla-miR-26a UUCAAGUAAUCCAGGAUAGGCU xtr-miR-l42-5p CAUAAAGUAGAAAGCACUAC

Ha-miR-28 AAGGAGCUCACAGUCUAUUGAG xtr-miR-143 UGAGAUGAAGCACUGUAGCUCG lla-miR-29a CUAGCACCAUCUGAAAUCGGUU xtr-miR-144 UACAGUAUAGAUGAUGUACUA

Ha-miR-29b UAGCACCAUUUGAAAUCAGU xtr-miR-145 GUCCAGUUUUCCCAGGAAUCCCUU lla-miR-30b UGUAAACAUCCUACACUCAGC xtr miR 146 UGAGAACUGAAUUCCAUAGGUU lla-nuR-30c UGUAAACAUCCUACACUCUCAGC xtr-miR-146b UGAGAACUGAAUUCCAUGGACU lla-miR-34a UGGCAGUGUCUUAGCUGGUUGU xtr-miR-148a UCAGUGCACUACAGAACUUUGU

Ha-miR-7 UGGAAGACUAGUGAUUUUGUU xtr-miR-148b UCAGUGCAUCACAGAACUUUGU

Ua-miR-9 UCUUUGGUUAUCUAGCUGUAUGA xtr-miR-150 UCUCCCAACCCUUGUACCAGAG

Ha-miR-92 UAUUGCACUUGUCCCGGCCUGU xtr-miR-153 UUGCAUAGUCACAAAAGUGA

Ua-miR-93 AAAGUGCUGUUCGUGCAGQUAG xtx-miR-155 UUAAUGCUAAUCGUGAUAGGGG lla-miR-95 UUCAACGGGUAUUUAUUGAGCA xtr-miR-15a UAGCAGCACAUAAUGGUUUGUG

Ua-miR-99a AACCCGUAGAUCCGAUCUUGUG xtr-miR-15b UAGCAGCACAUCAUGAUUUGCA mcmv-rπiR-mO 1 - 1 AGAGGAGAAUAACGUCGAACGG xtr-miR-15c UAGCAGCACAUCAUGGUUUGUA mcmv-miR-mOl-2 GAAGAGAAUCGGGUUGGAACGGU xtr-miR-16a UAGCAGCACGUAAAUAUUGGUG mcmv-miR-mOl-2* CGUUCGACACGGUUUCCUUCGA xtr-miR-16b UAGCAGCACGUAAAUAUUGGGU mcmv-miR-mO 1-3 CGGUGAAGCGACUGUUGCCUCGA xtr-miR 16c UAGCAGCACGUAAAUACUGGAG mcmv-miR-mOl-3* CGAGGAACGCUCGCUUCACGGC xt-miR-17-3p ACUGCAGUGAAGGCACUUGU mcmv-miR-mO 1 -4 UCCUAUGCUAACACGUGCGCGUG xtr-miR-17-5p CAAAGUGCUUACAGUGCAGGUAGU mcmv-miR-mOl-4* CGCCGCGUGGUAGCAUUAGAAC xtr miR-181a AACAUUCAACGCUGUCGGUGAGU mcmv-miR-m 107- 1 -3p UGCUCGCGUCGAGUGACCGCUC xtr miR 181a 1* ACCAUCGAUCGUUGACUGUACA momv miR-mlO7 1 Sp CGGUCACUCGUCUCGAGUCACC xtr-miR-181a-2* ACCAUCGGCCGUUGACUGUACC mcmv-rmR-m 108-1 UUUCUGACGGUGGCUCGUGUCG xtr-miR-lSlb AACAUUCAUUGCUGUCGGUGGG mcmv miR-m 108-1* UCACGAGCAACCGCCCGAAAUG xtr-miR-182 UUUGGCAAUGGUAGAACUCACA mcmv-miR ml 08 2 5p 1 GCGGUCACUCGACGCGAGCACCG xtr-miR-182* UGGUUCUAGACUUGCCAACUA mcmv miR-mlO8-2-5p 2 UCACUCGUCGCGAGCGGUCAC xtr-miR-183 UAUGGCACUGGUAGAAUUCACUG momv miR-m21-l AUAGGGGACACGUUCAAGCCG xtr-miR-184 UGGACGGAGAACUGAUAAGGCU mcmv-miR-m22- 1 UUCCCCGUCCGUACCGAGGCCA xtr-miR-187 UCGUGUCUUGUGUUGCAGCCA mcmv-miR-M23 - 1 -3p CUCCUGCGUCGGCCCGAGGCC xtr-miR-189 GUGCCUACUGAACUGAUAUCAGU mcmv miR M23-l-5p CUCGGUACGGACGGGGAACCGU xtr-miR-18a UAAGGUGCAUCUAGUGCAGAUAG mcmv-miR-M23-2 AUGGGGGCCUCGGUCAAGCGG xtr-miR-18a* ACUGCCCUAAGUGCUCCUUCU mcmv-miR-M23-2* UGAACGUGUCCCCUAUCGGUGG xtr-miR-18b UAAGGUGCAUCUAGUGCAGUUAG mcmv-miR-M44-l UAUCUUUUUCCAGAGCCGCGGU xtr-miR-191 CAACGGAAUCCCAAAAGCAGCU mcmv-miR-M55-l UGGUGAUCGGCGUGCUAGCCGU xtr-miR-192 AUGACCUAUGAAUUGACAGCC mcmv-miR-m59-l UUAGCAGUGCCUCGACCGUCAG xtr-miR-193 AACUGGCCCGCAAAGUCCCGCUUC mcmv-raiR-m59-2 CCCGAAGAGCCCUCACAGAGCC xtr-miR-194 UGUAACAGCAACUCCAUGUGGA mcmv-raiR-M87-l AGGCAGCCGUCGGCAGCGGCAGC xtr-miR-196a UAGGUAGUUUCAUGUUGUUGG mcmv miR-m88-l CAGAAGUCGAUGUCGGGGUCU xtr-miR-196b UAGGUAGUUUUAUGUUGUUGG mcmv-miR-mδ 8- 1 * AUGACCGACCCCCUGACAUCGG xtr-mιR-199a CCCAGUGUUCAGACUACCUGUUC mcmv-miR-M95-l-3p AGCGACGUCGGACCGCGACGGC xtr-miR-199a* UACAGUAGUCUGCACAUUGGUU momv-miR-M95-l-5p GGUCGUGGGCUUGUGUCGCUUG Xtr-miR-199b CCCAGUGUUCAGACUACGUGUUC mdo-let-7a UGAGGUAGUAGGUUGUAUAGUU xtr-miR-19a UGUGCAAAUCUAUGCAAAACUGA mdo-let-7b UGAGGUAGUAGGUUGUGUGGUU xtr-mιR-19b UGUGCAAAUCCAUGCAAAACUGA mdo-let-7d AGAGGUAGUAGGUUGCAUAGU xtτ-miR-la UGGAAUGUAAAGAAGUAUGUA mdo-let-7f UGAGGUAGUAGAUUGUAUAGUU xtr-miR Ib UGGAAUGUUAAGAAGUAUGUA mdo Iet-7g UGAGGUAGUAGUUUGUACAGU xtr-miR-200a UAACACUGUCUGGUAACGAUGU mdo-let-7i UGAGGUAGUAGUUUGUGCUGU xtr-miR-200b UAAUACUGCCUGGUAAUGAUGAU mdo miR-1 UGGAAUGUAAAGAAGUAUGUA xtr-miR-202 AGGGGCAUAGGGCAUGGGAAAA mdo miR 100 AACCCGUAGAUCCGAACUUGU xtr miR 202* UUUCCUAUGCAUAUACCUCUUU mdo miR 101 UACAGUACUGUGAUAACUGAAG xtr miR 203 GUGAAAUGUUUAGGACCACUUG mdo miR-103 AGCAGCAUUGUACAGGGCUAUGA xtr-miR-204 UUCCCUUUGUCAUCCUAUGCCU mdo miR-107 AGCAGCAUUGUACAGGGCUAUCA xtr-miR-205a UCCUUCAUUCCACCGGAGUCUG mdo miR-10a UACCCUGUAGAUCCGAAUUUGUG xtr-miR-205b UCCUUCAUUCCACCGGAUCCUG mdo miR-10b AUACCCUGUAGAACCGAAUUUGU xtr-miR-206 UGGAAUGUAAGGAAGUGUGUGG mdo miR-122 UGGAGUGUGACAAUGGUGUUUGUGU xtr-miR-208 AUAAGACGAGCAUAAAGCUUGU mdo miR 124a UUAAGGCACGCGGUGAAUGCCA xtr-miR-20a UAAAGUGCUUAUAGUGCAGGUAG mdo miR-125b UCCCUGAGACCCUAACUUGUGA xtr-miR-20a* ACUGCAUAAUGAGCACUUAAA mdo rruR-128 UCACAGUGAACCGGUCUCUUU xtr-miR-20b CAAAGUGCUCAUAGUGCAGGUAG mdo miR-129 CUUUUUGCGGUCUGGGCUUGCU xtr-πuR-210 CUGUGCGUGUGACAGCGGCUAA mdo miR-130a CAGUGCAAUGUAAAAAGGGCAU xtr-miR-212 UAACAGUCU ACAGUCAUGGCU mdo-miR-132 UAACAGUCUACAGCCAUGGUCG xtr-miR-214 ACAGCAGGCACAGACAGGCAG mdo-miR-133a UUGGUCCCCUUCAACCAGCUGU xtr-miR-215 AUGACCUAUGAAAUGACAGCC mdo miR-135a UAUGGCUUUUUAUUCCUAUGUGA xtr miR 216 UAAUCUCAGCUGGCAACUGUG mdo miR-135b UAUGGCUUUUCAUUCCUAUGUG xtr-miR-217 UACUGCAUCAGGAACUGAUUGGAU mdo-miR-137 UAUUGCUUAAGAAUACGCGUAG xtr-miR-218 UUGUGCUUGAUCUAACCAUGU mdo πuR-138 AGCUGGUGUUGUGAAUC xtr-miR-219 UGAUUGUCCAAACGCAAUUCU mdo-miR-141 UAACACUGUCUGGUAAAGAUGC xtr-miR-22 AAGCUGCCAGUUGAAGAACUGU mdo nuR-142 UGUAGUGUUUCCUACUUUAUGGA xtr-miR-22* AGUUCUUCAGUGGCAAGCUUU mdo miR-143 UGAGAUGAAGCACUGUAGCUCG xtr-miR-221 AGCUACAUUGUCUGCUGGGUUUC mdo-πuR-144 UACAGUAUAGAUGAUGUACUGG xtr-miR-222 AGCUACAUCUGGCUACUGGGUCUC mdo miR-145 GUCCAGUUUUCCCAGGAAUCCCU xtr-miR-223 UGUCAGUUUGUCAAAUACCCC mdo miR-152 UCAGUGCAUGACAGAACUUGGG xtr-miR-23a AUCACAUUGCCAGGGAUUUCC mdo miR-1540 UGAUUCCAUAGAGCGCAUGU xtr-miR-23b AUCACAUUGCCAGGGAUUACC mdo-miR-1541 UGQUGUGCUCGUUUGGAUGUGG xtr-mιR-24a UGGCUCAGUUCAGCAGGAACAG mdo miR-1542 UAUUGAUCUCCAAUGCCUAGC xtr-miR-24b UGGCUCAGUUCAGCAGGACAG mdo miR-1543 UUAGUCCUAGUCUAGGUGCACA xtr-πuR-25 CAUUGCACUUGUCUCGGUCUGA mdo-miR-1544 UGCACCCAGGGAUAGGAUAGCG xtr-miR-26 UUCAAGUAAUCCAGGAUAGGC mdo miR-1545 ACUUUCCAUCCCUUGCACUGU xtr miR 27a UUCACAGUGGCUAAGUUCCGC mdo miR-1546 UCAGGGAUUCUCAGGGAUGGAA xtr-πuR-27b UUCACAGUGGCUAAGUUCUGC mdo miR-1547 UAUCAGAGUCUUGGGUCCUUGU xtr πuR-27o UUCACAGUGGCUAAGUUCCAC mdo-miR-1548 UGCAUCCUGCAGCGGGCUCCCC xtτ-miR-29a UAGCACCAUUUGAAAUCGGUU mdo miR-1549 UUCCGCCCUGCAAGCCCGGUA xtr-πuR-29b UAGCACCAUUUGAAAUCAGUGUU mdo miR 15a UAGCAGCACAUAAUGGUUUGUU xtr-miR-29c UAGCACCAUUUGAAAUCGGU mdo miR 16 UAGCAGCACGUAAAUAUUGGCG xti-miR-29c* UGACCGAUCUCUCUUGGUGUUC mdo-miR 17 3p ACUGCAGUGAAGGCACUUGUA xtr-miR-29d UAGCACCAUAUGAAAUCAGUGUC mdo miR 17 5p CAAAGUGCUUACAGUGCAGGUAGU xtτ-πuR-301 CAGUGCAAUAGUAUUGUCAAAGC mdo-miR 18 UAAGGUGCAUCUAGUGCAGAUA xtr-miR-302 UAAGUGCUCCAAUGUUUUAGUGG mdo-miR 181a AACAUUCAACGCUGUCGGUGAGU xtr-miR-30a-3p CUUUCAGUCAGAUGUUUGCAGC mdo-miR-181b AACAUUCAUUGCUGUCGGUGGG xtr-miR-30a-5p UGUAAACAUCCUCGACUGGAAG mdo-miR-181c AACAUUCAACGCUGUCGGUGAGU xtr-miR-30b UGUAAACAUCCUACACUCAGCU mdo-miR-182 UUUGGCAAUGGUAGAACUCACA xtr-miR-30c UGUAAACAUCCUACACUCUCAGC rado-miR-183 UAUGGCACUGGUAGAAUUCACUG xtr-miR-30d UGUAAACAUCCCCGACUGGAAG mdo-miR-184 UGGACGGAGAACUGAUAAGGGU xtr-miR-30e UGUAAACAUCCUUGACUGGAAG mdo miR-186 CAAAGAAUUCUCCUUUUGGGCUU xtr miR 31 AGGCAAGAUGUUGGCAUAGCUG mdo-miR-187 UCGUGUCUUGUGUUGCAGCC xtr-miR-31b GGCAAGAUGCUGGCAAGCU mdo miR-191 CAACGGAAUCCCAAAAGCAGCU xtr-miR-320 AAAAGCUGGGUUGAGAGGUGA mdo miR-193 AACUGGCCUACAAAGUCCCAG xtr-miR-338 UCCAGCAUCAGUGAUUUUGUUG mdo-miR-196b UAGGUAGUUUCCUGUUGUUGG xtr-miR-33a GUGCAUUGUAGUUGCAUUG mdo-miR-199b CCCAGUGUUUAGACUAUCUGUUC xtr-miR-33b GUGCAUUGUUOUUGCAUUG mdo-miR-19a UQUGCAAAUCUAUGC AAAACUGA xtr-πuR-34a UGGCAGUGUCUUAGCUGGUUGUU mdo-miR-19b UGUGCAAAUCCAUGCAAAACUGA xtr-miR-34b CAGGCAGUGUAGUUAGCUGAUUG mdo-miR-20 UAAAGUGCUUAUAGUGCAGGUAG xtr miR 363 3p AAUUGCACGGUAUCCAUCUGU mdo-miR-200a UAACACUGUCUGGUAACGAUGU xtr-miR-363-5p CGGGUGGAUCACGAUGCAAUUU mdo miR-200a* CAUCUUACUAGACAGUGCUGGA xtr-πuR-365 UAAUGCCCCUAAAAAUCCUUAU mdo-miR-200b UAAUACUGCCUGGUAAUGAUGA xtr-miR-367 AAUUGCACUGUAGCAAUGGUGA mdo-miR-200c UAAUACUGCCGGGUAAUGAUGG xtr-miR-375 UUUGUUCGUUCGGCUCGCGUUA mdo miR-203 GUGAAAUGUUUAGGACCACUUG xtr-miR-383 AGAUCAGAAGGUGAUUGUGGCU mdo-miR-204 UUCCCUUUGUCAUCCUAUGCCU xtr-miR-425-5p AAUGACACGAUCACUCCCGUUGA mdo-miR-206 UGGAAUGUAAGGAAGUGUGUG xtr-miR-427 GAAAGUGCUUUCUGUUUUGGGCG mdo-miR-208 AUAAGACGAGCAAAAAGCUCGU xtr miR-428 UAAGUGCUCUCUAGUUCGGUUG mdo-miR-21 UAGCUUAUCAGACUGAUGUUGA xtr-m₁R-429 UAAUACUGUCUGGUAAUGCCGU mdo miR-212 UAACAGUCUCCAGUCACGGCC xtr-miR-449 AGGCAGUGUAAUGUUAGCUGGU mdo-miR-214 ACAGCAGGCACAGACAGGCAG xtr-miR-451 AAACCGUUACCAUU ACUGAGUU mdo-miR-216 UAAUCUCAGCUGGCAACUGUG xtr-miR-455 UAUGUGCCCUUGGACUACAUCG mdo-miR-217 UACUGCAUCAGGAACUGAUUGGAU xtr-miR-489 AGUGACAUCAUAUGUACGGCUGC mdo-miR-218 UUGUGCUUGAUCUAACCAUGU xtr πuR-499 UUAAGACUUGCAGUGAUGUUUAG mdo miR-219 UGAUUGUCCAAACGCAAUUCU xtr-πuR 7 UGGAAGACUAGUGAUUUUGUUG mdo-miR-22 AAGCUGCCAGUUGAAGAACUGC xtr miR 9 UCUUUGGUUAUCUAGCUGUAUG mdo miR-221 AGCUACAUUGUCUGCUGGGUUUC xtr-miR-9* UAAAGCUAGAUAACCGAAAGU mdo-miR-222a AGCUACAUCUGGCUACUGGGUCUC xtr-miR-92a UAUUGCACUUGUCCCGGCCUG mdo-miR-223 UGUCAGUUUGUCAAAUACCCC xtr-miR-92b UAUUGCACUCGUCCCGGCCUC mdo miR 23a AUCACAUUGCCAGGGAUUUC xtr-miR-93a AAAGUGCUGUUCGUGCAGGUAG mdo miR 23b AUCACAUUGCCAGGGAUUACC xtr-miR-93b AAGUGCUGUUCGUGCAGGUAG mdo miR 24 UGGCUCAGUUCAGCAG xtr-miR-96 UUUGGCACUAGCACAUUUUUGCU mdo-miR-25 CAUUGCACUUGUCUCGGUCUGA xtr-miR-98 UGAGGUAGUAAGUUGUAUUGUU mdo-miR-27a UUCACAGUGGCUAAGUUCCGC xtr-miR-99 AACCCGUAGAUCCGAUCUUGUG mdo-miR-27b UUCACAGUGGCUAAGUUCUGC xtr-πuR-9a UCUUUGGUUAUCUAGCUGUAUGA mdo-miR-29a UAGCACCAUUUGAAAUCGGU xtr-miR-9a* UAAAGCUAGAUAACCGAAAGU mdQ-miR-29b UAGCACCAUUUGAAAUCAGU xtr-miR-9b UCUUUGGUUACCUAGCUGUAUGA mdo-miR-302a UAAGUGCUUCCAUGUUUUAG xtr-miR-9b* UAAAGCUAGACAACCGAACGU indo-miR-302b UAAGUGCUUCCAUGUUUUGG

MIMAT0005561 mcmv-miR-mlO8-2-3p GUGACUCGAGACGAGUGACCGGU

Claims

1. A virus for use in a method of vaccination of a host, which virus is attenuated by means of one or more microRNA binding sequences which are present or encoded within the genome of the virus, wherein attenuation is achieved by the microRNA binding sequence(s) causing a reduction in the level of virus replication in host cells which express one or more microRNAs that bind to the microRNA binding sequence(s) present in the virus genome and/or mRNA.

2. A virus according to claim 1, wherein when the virus is present in the cell in which it is able to replicate, the virus expresses a mRNA that contains a microRNA binding site.

3. A virus according to claim 1 or 2 wherein at least one forward (sense) and/or at least one reverse (anti-sense) microRNA binding sequence is present in the genome of the virus and/or wherein the presence of the microRNA binding sequence destabilises the viral genome and/or wherein the presence of the microRNA binding sequence causes a decrease in viral integration into the host cell genome.

4. A virus according to any one of the preceding claims wherein microRNA binding sequences are present at two or more locations in the genome of the virus and/or wherein at each said location 1 to 30 microRNA binding sequences are present and/or wherein microRNA binding sequences are present in 3 ' UTR and/or 5' UTRs.

5. A virus according to any one of the preceding claims wherein microRNA binding sequences are inserted into the coding sequence of genes, decreased expression of which may, or may not, induce an increased immune response.

6. A virus according to any one of the preceding claims which has a DNA genome or a positive strand RNA genome.

7. A virus according to any one of claims 1 to 4 which has a negative strand RNA genome or double stranded RNA genome

8. A virus according to any one of claims 1 to 4 which has a linear, circular or linear segmented genome.

9. A method of making a virus as defined in any one of the preceding claims comprising inserting one or more microRNA binding sequences into the genome of a virus to thereby attenuate the virus, and optionally replicating the virus.

10. A viral genomic nucleic acid which comprises one or more microRNA binding sequences, which genomic nucleic acid is capable of causing attenuation of a virus into which it is present.

11. A vector nucleic acid for insertion into a viral genomic nucleic acid to produce the viral genomic nucleic acid of claim 10, wherein said vector comprises said microRNA binding sequence flanked by (i) at least 20 nucleotides of viral genomic sequence, and/or (ii) sufficient viral genomic sequence to allow insertion of the microRNA binding sequence into a genomic nucleic acid.

12. Use of a microRNA binding sequence to attenuate a virus.