CA2500523A1 - Vecteurs raav modifies par vp2 et leurs utilisations - Google Patents

Info

Publication number

CA2500523A1

CA2500523A1 CA002500523A CA2500523A CA2500523A1 CA 2500523 A1 CA2500523 A1 CA 2500523A1 CA 002500523 A CA002500523 A CA 002500523A CA 2500523 A CA2500523 A CA 2500523A CA 2500523 A1 CA2500523 A1 CA 2500523A1

Authority

CA

Canada

Prior art keywords

expression system

recombinant adeno

associated viral

promoter

protein

Prior art date

2003-05-01

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 239000013598 vector Substances 0.000 title claims abstract description 98
• 239000000203 mixture Substances 0.000 title claims description 99
• 239000002245 particle Substances 0.000 claims abstract description 264
• 108090000623 proteins and genes Proteins 0.000 claims abstract description 185
• 230000014509 gene expression Effects 0.000 claims abstract description 166
• 102000004169 proteins and genes Human genes 0.000 claims abstract description 136
• 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 86
• 230000003612 virological effect Effects 0.000 claims abstract description 80
• 108091092562 ribozyme Proteins 0.000 claims abstract description 77
• 102000053642 Catalytic RNA Human genes 0.000 claims abstract description 76
• 108090000994 Catalytic RNA Proteins 0.000 claims abstract description 76
• 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 44
• 210000002845 virion Anatomy 0.000 claims abstract description 43
• 241000282414 Homo sapiens Species 0.000 claims abstract description 32
• 229920001184 polypeptide Polymers 0.000 claims abstract description 32
• 241000124008 Mammalia Species 0.000 claims abstract description 21
• -1 host cells Substances 0.000 claims abstract description 16
• 239000000074 antisense oligonucleotide Substances 0.000 claims abstract description 8
• 238000012230 antisense oligonucleotides Methods 0.000 claims abstract description 8
• 101710081079 Minor spike protein H Proteins 0.000 claims abstract 4
• 210000004027 cell Anatomy 0.000 claims description 224
• 108090000565 Capsid Proteins Proteins 0.000 claims description 183
• 102100023321 Ceruloplasmin Human genes 0.000 claims description 177
• 230000035772 mutation Effects 0.000 claims description 136
• 235000018102 proteins Nutrition 0.000 claims description 130
• 230000027455 binding Effects 0.000 claims description 114
• 101710197658 Capsid protein VP1 Proteins 0.000 claims description 109
• 101710132601 Capsid protein Proteins 0.000 claims description 108
• 101710118046 RNA-directed RNA polymerase Proteins 0.000 claims description 108
• 101710108545 Viral protein 1 Proteins 0.000 claims description 108
• 150000007523 nucleic acids Chemical group 0.000 claims description 101
• 238000000034 method Methods 0.000 claims description 96
• 238000003780 insertion Methods 0.000 claims description 83
• 235000001014 amino acid Nutrition 0.000 claims description 82
• 102000039446 nucleic acids Human genes 0.000 claims description 81
• 108020004707 nucleic acids Proteins 0.000 claims description 81
• 230000037431 insertion Effects 0.000 claims description 79
• 150000001413 amino acids Chemical group 0.000 claims description 72
• 208000015181 infectious disease Diseases 0.000 claims description 65
• 238000004519 manufacturing process Methods 0.000 claims description 52
• 239000002157 polynucleotide Substances 0.000 claims description 43
• 102000040430 polynucleotide Human genes 0.000 claims description 42
• 108091033319 polynucleotide Proteins 0.000 claims description 42
• 230000002458 infectious effect Effects 0.000 claims description 37
• 239000002502 liposome Substances 0.000 claims description 37
• 239000013608 rAAV vector Substances 0.000 claims description 34
• 108091034117 Oligonucleotide Proteins 0.000 claims description 32
• 239000003623 enhancer Substances 0.000 claims description 31
• 238000001890 transfection Methods 0.000 claims description 31
• 239000003814 drug Substances 0.000 claims description 28
• 210000001519 tissue Anatomy 0.000 claims description 28
• 239000003446 ligand Substances 0.000 claims description 27
• 238000013518 transcription Methods 0.000 claims description 24
• 230000000692 anti-sense effect Effects 0.000 claims description 22
• 102000005962 receptors Human genes 0.000 claims description 22
• 108020003175 receptors Proteins 0.000 claims description 22
• 230000008685 targeting Effects 0.000 claims description 22
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
• 108091028043 Nucleic acid sequence Proteins 0.000 claims description 19
• 239000013604 expression vector Substances 0.000 claims description 17
• 201000010099 disease Diseases 0.000 claims description 16
• 239000013603 viral vector Substances 0.000 claims description 15
• 210000000056 organ Anatomy 0.000 claims description 14
• 229940124597 therapeutic agent Drugs 0.000 claims description 14
• 230000014616 translation Effects 0.000 claims description 14
• 239000012634 fragment Substances 0.000 claims description 13
• 238000002347 injection Methods 0.000 claims description 13
• 239000007924 injection Substances 0.000 claims description 13
• 150000002632 lipids Chemical class 0.000 claims description 13
• 210000004962 mammalian cell Anatomy 0.000 claims description 13
• 241000702421 Dependoparvovirus Species 0.000 claims description 12
• 102000008847 Serpin Human genes 0.000 claims description 11
• 108050000761 Serpin Proteins 0.000 claims description 11
• 239000003795 chemical substances by application Substances 0.000 claims description 11
• 230000001105 regulatory effect Effects 0.000 claims description 11
• 239000003001 serine protease inhibitor Substances 0.000 claims description 11
• 230000004064 dysfunction Effects 0.000 claims description 10
• 238000002560 therapeutic procedure Methods 0.000 claims description 9
• 230000007812 deficiency Effects 0.000 claims description 8
• 238000012217 deletion Methods 0.000 claims description 8
• 230000037430 deletion Effects 0.000 claims description 8
• 230000008488 polyadenylation Effects 0.000 claims description 8
• 208000024891 symptom Diseases 0.000 claims description 8
• 241001655883 Adeno-associated virus - 1 Species 0.000 claims description 7
• 241001634120 Adeno-associated virus - 5 Species 0.000 claims description 7
• 102000000844 Cell Surface Receptors Human genes 0.000 claims description 7
• 108010001857 Cell Surface Receptors Proteins 0.000 claims description 7
• 108700028146 Genetic Enhancer Elements Proteins 0.000 claims description 7
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 108020004705 Codon Proteins 0.000 claims description 6
• 102000004127 Cytokines Human genes 0.000 claims description 6
• 108090000695 Cytokines Proteins 0.000 claims description 6
• 206010028980 Neoplasm Diseases 0.000 claims description 6
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 6
• 229940079322 interferon Drugs 0.000 claims description 6
• 210000004185 liver Anatomy 0.000 claims description 6
• 239000002105 nanoparticle Substances 0.000 claims description 6
• 241000702423 Adeno-associated virus - 2 Species 0.000 claims description 5
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 5
• 210000004556 brain Anatomy 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 239000003112 inhibitor Substances 0.000 claims description 5
• 210000003734 kidney Anatomy 0.000 claims description 5
• 229930182817 methionine Natural products 0.000 claims description 5
• 239000004005 microsphere Substances 0.000 claims description 5
• 210000000496 pancreas Anatomy 0.000 claims description 5
• 241000202702 Adeno-associated virus - 3 Species 0.000 claims description 4
• 102000014150 Interferons Human genes 0.000 claims description 4
• 108010050904 Interferons Proteins 0.000 claims description 4
• 241001529936 Murinae Species 0.000 claims description 4
• 208000006011 Stroke Diseases 0.000 claims description 4
• 239000000427 antigen Substances 0.000 claims description 4
• 108091007433 antigens Proteins 0.000 claims description 4
• 102000036639 antigens Human genes 0.000 claims description 4
• 239000000872 buffer Substances 0.000 claims description 4
• 201000011510 cancer Diseases 0.000 claims description 4
• 230000001939 inductive effect Effects 0.000 claims description 4
• 210000003061 neural cell Anatomy 0.000 claims description 4
• 230000001124 posttranscriptional effect Effects 0.000 claims description 4
• 208000023275 Autoimmune disease Diseases 0.000 claims description 3
• 241000283690 Bos taurus Species 0.000 claims description 3
• 241000282465 Canis Species 0.000 claims description 3
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
• 241000283073 Equus caballus Species 0.000 claims description 3
• 241000282324 Felis Species 0.000 claims description 3
• 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 claims description 3
• 108090001061 Insulin Proteins 0.000 claims description 3
• 102000000588 Interleukin-2 Human genes 0.000 claims description 3
• 108010002350 Interleukin-2 Proteins 0.000 claims description 3
• 208000019693 Lung disease Diseases 0.000 claims description 3
• 208000018737 Parkinson disease Diseases 0.000 claims description 3
• 241000288906 Primates Species 0.000 claims description 3
• 102100040247 Tumor necrosis factor Human genes 0.000 claims description 3
• 125000000539 amino acid group Chemical group 0.000 claims description 3
• 239000008280 blood Substances 0.000 claims description 3
• 230000006735 deficit Effects 0.000 claims description 3
• 206010012601 diabetes mellitus Diseases 0.000 claims description 3
• 229940088597 hormone Drugs 0.000 claims description 3
• 239000005556 hormone Substances 0.000 claims description 3
• 229940125396 insulin Drugs 0.000 claims description 3
• 208000028867 ischemia Diseases 0.000 claims description 3
• 208000017169 kidney disease Diseases 0.000 claims description 3
• 208000019423 liver disease Diseases 0.000 claims description 3
• 239000011859 microparticle Substances 0.000 claims description 3
• 210000003205 muscle Anatomy 0.000 claims description 3
• 239000002077 nanosphere Substances 0.000 claims description 3
• 230000001537 neural effect Effects 0.000 claims description 3
• 102000003886 Glycoproteins Human genes 0.000 claims description 2
• 108090000288 Glycoproteins Proteins 0.000 claims description 2
• 241000219745 Lupinus Species 0.000 claims description 2
• 241001492404 Woodchuck hepatitis virus Species 0.000 claims description 2
• 210000000988 bone and bone Anatomy 0.000 claims description 2
• 108010006025 bovine growth hormone Proteins 0.000 claims description 2
• 108091008039 hormone receptors Proteins 0.000 claims description 2
• 229940124531 pharmaceutical excipient Drugs 0.000 claims description 2
• 229920000642 polymer Polymers 0.000 claims description 2
• 108010025020 Nerve Growth Factor Proteins 0.000 claims 5
• 230000037433 frameshift Effects 0.000 claims 5
• 208000012902 Nervous system disease Diseases 0.000 claims 4
• 208000025966 Neurological disease Diseases 0.000 claims 4
• 102000004219 Brain-derived neurotrophic factor Human genes 0.000 claims 3
• 108090000715 Brain-derived neurotrophic factor Proteins 0.000 claims 3
• 108090000174 Interleukin-10 Proteins 0.000 claims 3
• 102000015336 Nerve Growth Factor Human genes 0.000 claims 3
• 239000003102 growth factor Substances 0.000 claims 3
• 210000004072 lung Anatomy 0.000 claims 3
• 208000024827 Alzheimer disease Diseases 0.000 claims 2
• 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 claims 2
• 102100031614 Ciliary neurotrophic factor Human genes 0.000 claims 2
• 208000030814 Eating disease Diseases 0.000 claims 2
• 208000019454 Feeding and Eating disease Diseases 0.000 claims 2
• 208000023105 Huntington disease Diseases 0.000 claims 2
• 102000015696 Interleukins Human genes 0.000 claims 2
• 108010063738 Interleukins Proteins 0.000 claims 2
• 102000007072 Nerve Growth Factors Human genes 0.000 claims 2
• 208000016222 Pancreatic disease Diseases 0.000 claims 2
• 102100035846 Pigment epithelium-derived factor Human genes 0.000 claims 2
• 102000001253 Protein Kinase Human genes 0.000 claims 2
• 102000014105 Semaphorin Human genes 0.000 claims 2
• 108050003978 Semaphorin Proteins 0.000 claims 2
• 102000009618 Transforming Growth Factors Human genes 0.000 claims 2
• 108010009583 Transforming Growth Factors Proteins 0.000 claims 2
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims 2
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims 2
• 235000014632 disordered eating Nutrition 0.000 claims 2
• 210000002216 heart Anatomy 0.000 claims 2
• 230000001272 neurogenic effect Effects 0.000 claims 2
• 208000018360 neuromuscular disease Diseases 0.000 claims 2
• 108090000102 pigment epithelium-derived factor Proteins 0.000 claims 2
• 108060006633 protein kinase Proteins 0.000 claims 2
• 230000002797 proteolythic effect Effects 0.000 claims 2
• 230000002792 vascular Effects 0.000 claims 2
• JVJUWEFOGFCHKR-UHFFFAOYSA-N 2-(diethylamino)ethyl 1-(3,4-dimethylphenyl)cyclopentane-1-carboxylate;hydrochloride Chemical compound Cl.C=1C=C(C)C(C)=CC=1C1(C(=O)OCCN(CC)CC)CCCC1 JVJUWEFOGFCHKR-UHFFFAOYSA-N 0.000 claims 1
• 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 claims 1
• 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 claims 1
• 241000580270 Adeno-associated virus - 4 Species 0.000 claims 1
• 241000972680 Adeno-associated virus - 6 Species 0.000 claims 1
• 229940088872 Apoptosis inhibitor Drugs 0.000 claims 1
• 208000023328 Basedow disease Diseases 0.000 claims 1
• 208000020084 Bone disease Diseases 0.000 claims 1
• 102000004031 Carboxy-Lyases Human genes 0.000 claims 1
• 108090000489 Carboxy-Lyases Proteins 0.000 claims 1
• 102000014914 Carrier Proteins Human genes 0.000 claims 1
• 108010078791 Carrier Proteins Proteins 0.000 claims 1
• 101710112752 Cytotoxin Proteins 0.000 claims 1
• 102000002149 Elafin Human genes 0.000 claims 1
• 108010015972 Elafin Proteins 0.000 claims 1
• 102000008214 Glutamate decarboxylase Human genes 0.000 claims 1
• 108091022930 Glutamate decarboxylase Proteins 0.000 claims 1
• 102000006771 Gonadotropins Human genes 0.000 claims 1
• 108010086677 Gonadotropins Proteins 0.000 claims 1
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 claims 1
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 claims 1
• 208000015023 Graves' disease Diseases 0.000 claims 1
• 102000009465 Growth Factor Receptors Human genes 0.000 claims 1
• 108010009202 Growth Factor Receptors Proteins 0.000 claims 1
• 108010051696 Growth Hormone Proteins 0.000 claims 1
• 101000959820 Homo sapiens Interferon alpha-1/13 Proteins 0.000 claims 1
• 102220467374 Hypoxia-inducible lipid droplet-associated protein_I87A_mutation Human genes 0.000 claims 1
• 102100023915 Insulin Human genes 0.000 claims 1
• 102100040019 Interferon alpha-1/13 Human genes 0.000 claims 1
• 108010002352 Interleukin-1 Proteins 0.000 claims 1
• 102000000589 Interleukin-1 Human genes 0.000 claims 1
• 108090000177 Interleukin-11 Proteins 0.000 claims 1
• 108010065805 Interleukin-12 Proteins 0.000 claims 1
• 108090000176 Interleukin-13 Proteins 0.000 claims 1
• 102000013691 Interleukin-17 Human genes 0.000 claims 1
• 108050003558 Interleukin-17 Proteins 0.000 claims 1
• 108010002386 Interleukin-3 Proteins 0.000 claims 1
• 108090000978 Interleukin-4 Proteins 0.000 claims 1
• 108010002616 Interleukin-5 Proteins 0.000 claims 1
• 108090001005 Interleukin-6 Proteins 0.000 claims 1
• 108010002586 Interleukin-7 Proteins 0.000 claims 1
• 108090001007 Interleukin-8 Proteins 0.000 claims 1
• 108010002335 Interleukin-9 Proteins 0.000 claims 1
• 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 claims 1
• 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 claims 1
• 208000010316 Myotonia congenita Diseases 0.000 claims 1
• 102000007339 Nerve Growth Factor Receptors Human genes 0.000 claims 1
• 108010032605 Nerve Growth Factor Receptors Proteins 0.000 claims 1
• 108010063605 Netrins Proteins 0.000 claims 1
• 102000010803 Netrins Human genes 0.000 claims 1
• 102000002111 Neuropilin Human genes 0.000 claims 1
• 108050009450 Neuropilin Proteins 0.000 claims 1
• 108091005804 Peptidases Proteins 0.000 claims 1
• 102000012288 Phosphopyruvate Hydratase Human genes 0.000 claims 1
• 108010022181 Phosphopyruvate Hydratase Proteins 0.000 claims 1
• 102000003946 Prolactin Human genes 0.000 claims 1
• 108010057464 Prolactin Proteins 0.000 claims 1
• 239000004365 Protease Substances 0.000 claims 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims 1
• 108091081062 Repeated sequence (DNA) Proteins 0.000 claims 1
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 1
• 102100038803 Somatotropin Human genes 0.000 claims 1
• 102000001742 Tumor Suppressor Proteins Human genes 0.000 claims 1
• 108010040002 Tumor Suppressor Proteins Proteins 0.000 claims 1
• 239000000048 adrenergic agonist Substances 0.000 claims 1
• 102000015395 alpha 1-Antitrypsin Human genes 0.000 claims 1
• 108010050122 alpha 1-Antitrypsin Proteins 0.000 claims 1
• 229940024142 alpha 1-antitrypsin Drugs 0.000 claims 1
• 230000006909 anti-apoptosis Effects 0.000 claims 1
• 239000000158 apoptosis inhibitor Substances 0.000 claims 1
• 210000003050 axon Anatomy 0.000 claims 1
• 210000000601 blood cell Anatomy 0.000 claims 1
• 210000002449 bone cell Anatomy 0.000 claims 1
• 210000004958 brain cell Anatomy 0.000 claims 1
• 210000003169 central nervous system Anatomy 0.000 claims 1
• 201000011474 congenital myopathy Diseases 0.000 claims 1
• 102000003675 cytokine receptors Human genes 0.000 claims 1
• 108010057085 cytokine receptors Proteins 0.000 claims 1
• 231100000599 cytotoxic agent Toxicity 0.000 claims 1
• 239000002619 cytotoxin Substances 0.000 claims 1
• 210000001787 dendrite Anatomy 0.000 claims 1
• MDCUNMLZLNGCQA-HWOAGHQOSA-N elafin Chemical compound N([C@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H]1C(=O)N2CCC[C@H]2C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H]2CSSC[C@H]3C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](CSSC[C@H]4C(=O)N5CCC[C@H]5C(=O)NCC(=O)N[C@H](C(N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H]5N(CCC5)C(=O)[C@H]5N(CCC5)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC2=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N4)C(=O)N[C@@H](CSSC1)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N3)=O)[C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(O)=O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)C(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)N MDCUNMLZLNGCQA-HWOAGHQOSA-N 0.000 claims 1
• 230000003511 endothelial effect Effects 0.000 claims 1
• 230000000913 erythropoietic effect Effects 0.000 claims 1
• 239000002622 gonadotropin Substances 0.000 claims 1
• 208000014951 hematologic disease Diseases 0.000 claims 1
• 208000018706 hematopoietic system disease Diseases 0.000 claims 1
• 230000000971 hippocampal effect Effects 0.000 claims 1
• 102000002467 interleukin receptors Human genes 0.000 claims 1
• 108010093036 interleukin receptors Proteins 0.000 claims 1
• 210000004153 islets of langerhan Anatomy 0.000 claims 1
• 210000003292 kidney cell Anatomy 0.000 claims 1
• 229940043355 kinase inhibitor Drugs 0.000 claims 1
• 210000000663 muscle cell Anatomy 0.000 claims 1
• 208000010125 myocardial infarction Diseases 0.000 claims 1
• 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 claims 1
• 229940053128 nerve growth factor Drugs 0.000 claims 1
• 239000003900 neurotrophic factor Substances 0.000 claims 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 claims 1
• 108010011903 peptide receptors Proteins 0.000 claims 1
• 102000014187 peptide receptors Human genes 0.000 claims 1
• 210000001428 peripheral nervous system Anatomy 0.000 claims 1
• 239000003757 phosphotransferase inhibitor Substances 0.000 claims 1
• 102000002022 plexin Human genes 0.000 claims 1
• 108050009312 plexin Proteins 0.000 claims 1
• 229940097325 prolactin Drugs 0.000 claims 1
• 239000012268 protein inhibitor Substances 0.000 claims 1
• 229940121649 protein inhibitor Drugs 0.000 claims 1
• 230000018883 protein targeting Effects 0.000 claims 1
• 230000013275 serotonin uptake Effects 0.000 claims 1
• 239000003772 serotonin uptake inhibitor Substances 0.000 claims 1
• 210000003491 skin Anatomy 0.000 claims 1
• 241000700605 Viruses Species 0.000 abstract description 94
• 230000001225 therapeutic effect Effects 0.000 abstract description 29
• 239000008194 pharmaceutical composition Substances 0.000 abstract description 13
• 230000001976 improved effect Effects 0.000 abstract description 10
• 108020000948 Antisense Oligonucleotides Proteins 0.000 abstract description 4
• 210000000234 capsid Anatomy 0.000 description 105
• 108020004414 DNA Proteins 0.000 description 98
• HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 98
• 239000013612 plasmid Substances 0.000 description 95
• 229920000669 heparin Polymers 0.000 description 72
• 229960002897 heparin Drugs 0.000 description 72
• 229940024606 amino acid Drugs 0.000 description 70
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 58
• 239000005090 green fluorescent protein Substances 0.000 description 48
• 108010043121 Green Fluorescent Proteins Proteins 0.000 description 45
• 102000004144 Green Fluorescent Proteins Human genes 0.000 description 45
• 230000000295 complement effect Effects 0.000 description 39
• 230000015572 biosynthetic process Effects 0.000 description 38
• 230000003321 amplification Effects 0.000 description 36
• 210000001072 colon Anatomy 0.000 description 36
• 238000003199 nucleic acid amplification method Methods 0.000 description 36
• 239000000523 sample Substances 0.000 description 36
• 229920000936 Agarose Polymers 0.000 description 33
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
• 230000002950 deficient Effects 0.000 description 33
• 230000000694 effects Effects 0.000 description 31
• 229920002971 Heparan sulfate Polymers 0.000 description 30
• 238000005755 formation reaction Methods 0.000 description 30
• 238000002360 preparation method Methods 0.000 description 30
• 238000001262 western blot Methods 0.000 description 30
• 108091081024 Start codon Proteins 0.000 description 27
• 238000010361 transduction Methods 0.000 description 27
• 230000026683 transduction Effects 0.000 description 27
• 108020004999 messenger RNA Proteins 0.000 description 26
• 150000001875 compounds Chemical class 0.000 description 25
• 239000000047 product Substances 0.000 description 25
• 238000000746 purification Methods 0.000 description 25
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 24
• 238000004458 analytical method Methods 0.000 description 24
• NBQNWMBBSKPBAY-UHFFFAOYSA-N iodixanol Chemical compound IC=1C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C(I)C=1N(C(=O)C)CC(O)CN(C(C)=O)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NBQNWMBBSKPBAY-UHFFFAOYSA-N 0.000 description 23
• 229960004359 iodixanol Drugs 0.000 description 23
• 125000003729 nucleotide group Chemical group 0.000 description 23
• 238000006467 substitution reaction Methods 0.000 description 23
• 230000035897 transcription Effects 0.000 description 23
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
• 239000002773 nucleotide Substances 0.000 description 20
• 125000003275 alpha amino acid group Chemical group 0.000 description 19
• 238000003119 immunoblot Methods 0.000 description 19
• 230000004048 modification Effects 0.000 description 19
• 238000012986 modification Methods 0.000 description 19
• 238000012384 transportation and delivery Methods 0.000 description 19
• 108091026890 Coding region Proteins 0.000 description 18
• 238000003556 assay Methods 0.000 description 18
• 230000002255 enzymatic effect Effects 0.000 description 18
• 238000009472 formulation Methods 0.000 description 18
• 238000006243 chemical reaction Methods 0.000 description 17
• 239000013607 AAV vector Substances 0.000 description 16
• 241001465754 Metazoa Species 0.000 description 16
• 239000000020 Nitrocellulose Substances 0.000 description 16
• 230000003993 interaction Effects 0.000 description 16
• 229920001220 nitrocellulos Polymers 0.000 description 16
• 238000002703 mutagenesis Methods 0.000 description 15
• 231100000350 mutagenesis Toxicity 0.000 description 15
• 102000053602 DNA Human genes 0.000 description 14
• 235000004279 alanine Nutrition 0.000 description 14
• 229940039781 leptin Drugs 0.000 description 14
• 108010092277 Leptin Proteins 0.000 description 13
• 102000016267 Leptin Human genes 0.000 description 13
• 239000002585 base Substances 0.000 description 13
• 230000006870 function Effects 0.000 description 13
• 230000008569 process Effects 0.000 description 13
• 239000000243 solution Substances 0.000 description 13
• 238000011282 treatment Methods 0.000 description 13
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 12
• 230000008901 benefit Effects 0.000 description 12
• 238000001415 gene therapy Methods 0.000 description 12
• NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 12
• 238000013459 approach Methods 0.000 description 11
• 241000701022 Cytomegalovirus Species 0.000 description 10
• 241001135569 Human adenovirus 5 Species 0.000 description 10
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 10
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 10
• 239000004472 Lysine Substances 0.000 description 10
• 230000007547 defect Effects 0.000 description 10
• 238000012239 gene modification Methods 0.000 description 10
• 108010038082 heparin proteoglycan Proteins 0.000 description 10
• 238000002741 site-directed mutagenesis Methods 0.000 description 10
• 238000013519 translation Methods 0.000 description 10
• 230000010415 tropism Effects 0.000 description 10
• 230000003682 DNA packaging effect Effects 0.000 description 9
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 9
• 102000004190 Enzymes Human genes 0.000 description 9
• 108090000790 Enzymes Proteins 0.000 description 9
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 9
• 230000001413 cellular effect Effects 0.000 description 9
• 229940088598 enzyme Drugs 0.000 description 9
• 230000002068 genetic effect Effects 0.000 description 9
• 230000005017 genetic modification Effects 0.000 description 9
• 235000013617 genetically modified food Nutrition 0.000 description 9
• 230000001965 increasing effect Effects 0.000 description 9
• 239000003550 marker Substances 0.000 description 9
• 239000012528 membrane Substances 0.000 description 9
• 210000004379 membrane Anatomy 0.000 description 9
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
• 241000251131 Sphyrna Species 0.000 description 8
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 8
• 235000009697 arginine Nutrition 0.000 description 8
• 230000001419 dependent effect Effects 0.000 description 8
• 238000001514 detection method Methods 0.000 description 8
• 239000000499 gel Substances 0.000 description 8
• 239000008188 pellet Substances 0.000 description 8
• 238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 8
• 238000003786 synthesis reaction Methods 0.000 description 8
• 239000003981 vehicle Substances 0.000 description 8
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
• 239000012130 whole-cell lysate Substances 0.000 description 8
• 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 7
• 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 7
• 238000002965 ELISA Methods 0.000 description 7
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 7
• 150000001251 acridines Chemical class 0.000 description 7
• 238000007792 addition Methods 0.000 description 7
• 238000003776 cleavage reaction Methods 0.000 description 7
• 238000010276 construction Methods 0.000 description 7
• 235000006109 methionine Nutrition 0.000 description 7
• 230000007017 scission Effects 0.000 description 7
• 241000701161 unidentified adenovirus Species 0.000 description 7
• 102000040650 (ribonucleotides)n+m Human genes 0.000 description 6
• 239000004475 Arginine Substances 0.000 description 6
• 101150044789 Cap gene Proteins 0.000 description 6
• 102100020997 Fractalkine Human genes 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• 108700026244 Open Reading Frames Proteins 0.000 description 6
• 108700008625 Reporter Genes Proteins 0.000 description 6
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 6
• 238000011161 development Methods 0.000 description 6
• 230000018109 developmental process Effects 0.000 description 6
• 229940079593 drug Drugs 0.000 description 6
• 238000002474 experimental method Methods 0.000 description 6
• 238000002955 isolation Methods 0.000 description 6
• 238000011084 recovery Methods 0.000 description 6
• 230000002829 reductive effect Effects 0.000 description 6
• 239000000758 substrate Substances 0.000 description 6
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 5
• 101001007348 Arachis hypogaea Galactose-binding lectin Proteins 0.000 description 5
• 108010019957 Escherichia coli periplasmic proteinase Proteins 0.000 description 5
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 5
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 5
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 5
• 229910019142 PO4 Inorganic materials 0.000 description 5
• 108020004682 Single-Stranded DNA Proteins 0.000 description 5
• 102000040945 Transcription factor Human genes 0.000 description 5
• 108091023040 Transcription factor Proteins 0.000 description 5
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 5
• 230000009471 action Effects 0.000 description 5
• 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 5
• 238000010367 cloning Methods 0.000 description 5
• 230000000875 corresponding effect Effects 0.000 description 5
• 238000010586 diagram Methods 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 239000006185 dispersion Substances 0.000 description 5
• 230000008030 elimination Effects 0.000 description 5
• 238000003379 elimination reaction Methods 0.000 description 5
• 238000000799 fluorescence microscopy Methods 0.000 description 5
• 230000004927 fusion Effects 0.000 description 5
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 5
• 230000000977 initiatory effect Effects 0.000 description 5
• 238000002743 insertional mutagenesis Methods 0.000 description 5
• 230000002452 interceptive effect Effects 0.000 description 5
• 238000007918 intramuscular administration Methods 0.000 description 5
• 230000001404 mediated effect Effects 0.000 description 5
• 230000035699 permeability Effects 0.000 description 5
• 235000021317 phosphate Nutrition 0.000 description 5
• 230000002265 prevention Effects 0.000 description 5
• 238000000159 protein binding assay Methods 0.000 description 5
• 230000002441 reversible effect Effects 0.000 description 5
• 150000003839 salts Chemical class 0.000 description 5
• 210000002966 serum Anatomy 0.000 description 5
• 239000013638 trimer Substances 0.000 description 5
• YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 4
• ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 4
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 4
• 108010067770 Endopeptidase K Proteins 0.000 description 4
• 102100034343 Integrase Human genes 0.000 description 4
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 4
• 108010077850 Nuclear Localization Signals Proteins 0.000 description 4
• 230000006819 RNA synthesis Effects 0.000 description 4
• 108010083644 Ribonucleases Proteins 0.000 description 4
• 102000006382 Ribonucleases Human genes 0.000 description 4
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 4
• 238000002105 Southern blotting Methods 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 4
• 239000004473 Threonine Substances 0.000 description 4
• 239000002253 acid Substances 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 4
• 235000009582 asparagine Nutrition 0.000 description 4
• 229960001230 asparagine Drugs 0.000 description 4
• 239000012298 atmosphere Substances 0.000 description 4
• 230000001580 bacterial effect Effects 0.000 description 4
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
• 238000004440 column chromatography Methods 0.000 description 4
• 230000002596 correlated effect Effects 0.000 description 4
• 230000001351 cycling effect Effects 0.000 description 4
• 230000007423 decrease Effects 0.000 description 4
• 238000005516 engineering process Methods 0.000 description 4
• 238000009396 hybridization Methods 0.000 description 4
• 238000010348 incorporation Methods 0.000 description 4
• 230000005764 inhibitory process Effects 0.000 description 4
• 239000000543 intermediate Substances 0.000 description 4
• 238000001990 intravenous administration Methods 0.000 description 4
• PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 4
• 229960000310 isoleucine Drugs 0.000 description 4
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 230000007246 mechanism Effects 0.000 description 4
• 239000002088 nanocapsule Substances 0.000 description 4
• 210000004940 nucleus Anatomy 0.000 description 4
• 238000004806 packaging method and process Methods 0.000 description 4
• PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 4
• 239000002644 phorbol ester Substances 0.000 description 4
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 4
• 239000011541 reaction mixture Substances 0.000 description 4
• 230000010076 replication Effects 0.000 description 4
• 230000003362 replicative effect Effects 0.000 description 4
• 108091008146 restriction endonucleases Proteins 0.000 description 4
• 238000003757 reverse transcription PCR Methods 0.000 description 4
• DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 4
• 241000894007 species Species 0.000 description 4
• UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 238000012360 testing method Methods 0.000 description 4
• 230000002103 transcriptional effect Effects 0.000 description 4
• 238000012546 transfer Methods 0.000 description 4
• 230000014621 translational initiation Effects 0.000 description 4
• 241000701447 unidentified baculovirus Species 0.000 description 4
• 239000004474 valine Substances 0.000 description 4
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
• 108091016585 CD44 antigen Proteins 0.000 description 3
• 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 3
• 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 3
• 239000004471 Glycine Substances 0.000 description 3
• 102000008055 Heparan Sulfate Proteoglycans Human genes 0.000 description 3
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
• 102000015439 Phospholipases Human genes 0.000 description 3
• 108010064785 Phospholipases Proteins 0.000 description 3
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 3
• 108020004511 Recombinant DNA Proteins 0.000 description 3
• 108091081021 Sense strand Proteins 0.000 description 3
• 108010034546 Serratia marcescens nuclease Proteins 0.000 description 3
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• 101710172711 Structural protein Proteins 0.000 description 3
• 108090000054 Syndecan-2 Proteins 0.000 description 3
• 108700029229 Transcriptional Regulatory Elements Proteins 0.000 description 3
• 108700019146 Transgenes Proteins 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
• 108020005202 Viral DNA Proteins 0.000 description 3
• 208000036142 Viral infection Diseases 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• 230000004075 alteration Effects 0.000 description 3
• 229940009098 aspartate Drugs 0.000 description 3
• DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 3
• 238000004422 calculation algorithm Methods 0.000 description 3
• 230000015556 catabolic process Effects 0.000 description 3
• 230000003197 catalytic effect Effects 0.000 description 3
• 239000013592 cell lysate Substances 0.000 description 3
• 238000005119 centrifugation Methods 0.000 description 3
• 230000008859 change Effects 0.000 description 3
• 238000012512 characterization method Methods 0.000 description 3
• 239000003153 chemical reaction reagent Substances 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 239000002299 complementary DNA Substances 0.000 description 3
• 230000008878 coupling Effects 0.000 description 3
• 238000010168 coupling process Methods 0.000 description 3
• 238000005859 coupling reaction Methods 0.000 description 3
• 125000004122 cyclic group Chemical group 0.000 description 3
• 235000018417 cysteine Nutrition 0.000 description 3
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
• 238000006731 degradation reaction Methods 0.000 description 3
• 239000002612 dispersion medium Substances 0.000 description 3
• 238000001962 electrophoresis Methods 0.000 description 3
• 210000003527 eukaryotic cell Anatomy 0.000 description 3
• 239000012530 fluid Substances 0.000 description 3
• 238000001476 gene delivery Methods 0.000 description 3
• 229930195712 glutamate Natural products 0.000 description 3
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 3
• 210000005260 human cell Anatomy 0.000 description 3
• 238000001802 infusion Methods 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 3
• 239000011159 matrix material Substances 0.000 description 3
• 150000002742 methionines Chemical class 0.000 description 3
• 244000005700 microbiome Species 0.000 description 3
• 230000002018 overexpression Effects 0.000 description 3
• 239000010452 phosphate Substances 0.000 description 3
• 150000003904 phospholipids Chemical class 0.000 description 3
• 229920001223 polyethylene glycol Polymers 0.000 description 3
• 238000006116 polymerization reaction Methods 0.000 description 3
• 239000000843 powder Substances 0.000 description 3
• 239000013645 rAAV1 vector Substances 0.000 description 3
• 108010054624 red fluorescent protein Proteins 0.000 description 3
• 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 3
• 238000000926 separation method Methods 0.000 description 3
• 239000002904 solvent Substances 0.000 description 3
• 210000000952 spleen Anatomy 0.000 description 3
• 235000000346 sugar Nutrition 0.000 description 3
• 230000007704 transition Effects 0.000 description 3
• 230000032258 transport Effects 0.000 description 3
• 238000011269 treatment regimen Methods 0.000 description 3
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
• 230000009385 viral infection Effects 0.000 description 3
• CJDRUOGAGYHKKD-XMTJACRCSA-N (+)-Ajmaline Natural products O[C@H]1[C@@H](CC)[C@@H]2[C@@H]3[C@H](O)[C@@]45[C@@H](N(C)c6c4cccc6)[C@@H](N1[C@H]3C5)C2 CJDRUOGAGYHKKD-XMTJACRCSA-N 0.000 description 2
• HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
• 108020005544 Antisense RNA Proteins 0.000 description 2
• 208000035143 Bacterial infection Diseases 0.000 description 2
• 102100021590 Bcl-2-like protein 10 Human genes 0.000 description 2
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
• 101000909256 Caldicellulosiruptor bescii (strain ATCC BAA-1888 / DSM 6725 / Z-1320) DNA polymerase I Proteins 0.000 description 2
• 241000701931 Canine parvovirus Species 0.000 description 2
• 108010012236 Chemokines Proteins 0.000 description 2
• 102000019034 Chemokines Human genes 0.000 description 2
• 108060005980 Collagenase Proteins 0.000 description 2
• 102000029816 Collagenase Human genes 0.000 description 2
• 201000003883 Cystic fibrosis Diseases 0.000 description 2
• NYHBQMYGNKIUIF-UHFFFAOYSA-N D-guanosine Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(CO)C(O)C1O NYHBQMYGNKIUIF-UHFFFAOYSA-N 0.000 description 2
• 101710177611 DNA polymerase II large subunit Proteins 0.000 description 2
• 101710184669 DNA polymerase II small subunit Proteins 0.000 description 2
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
• 238000012286 ELISA Assay Methods 0.000 description 2
• 108010042407 Endonucleases Proteins 0.000 description 2
• 241000588724 Escherichia coli Species 0.000 description 2
• 108091029865 Exogenous DNA Proteins 0.000 description 2
• 229920002527 Glycogen Polymers 0.000 description 2
• 229920002683 Glycosaminoglycan Polymers 0.000 description 2
• 108091027874 Group I catalytic intron Proteins 0.000 description 2
• NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 2
• 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 2
• 241000700721 Hepatitis B virus Species 0.000 description 2
• 108091027305 Heteroduplex Proteins 0.000 description 2
• 241000238631 Hexapoda Species 0.000 description 2
• 101000971082 Homo sapiens Bcl-2-like protein 10 Proteins 0.000 description 2
• 101000854520 Homo sapiens Fractalkine Proteins 0.000 description 2
• 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 2
• 101000903318 Homo sapiens Stress-70 protein, mitochondrial Proteins 0.000 description 2
• 108060003951 Immunoglobulin Proteins 0.000 description 2
• 102000004877 Insulin Human genes 0.000 description 2
• 101710203526 Integrase Proteins 0.000 description 2
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 2
• 102000003960 Ligases Human genes 0.000 description 2
• 108090000364 Ligases Proteins 0.000 description 2
• 239000000232 Lipid Bilayer Substances 0.000 description 2
• 102000043131 MHC class II family Human genes 0.000 description 2
• 108091054438 MHC class II family Proteins 0.000 description 2
• 101710125418 Major capsid protein Proteins 0.000 description 2
• 241000714177 Murine leukemia virus Species 0.000 description 2
• 241000699666 Mus <mouse, genus> Species 0.000 description 2
• 241000221960 Neurospora Species 0.000 description 2
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
• 108700020796 Oncogene Proteins 0.000 description 2
• 102000043276 Oncogene Human genes 0.000 description 2
• 229930182555 Penicillin Natural products 0.000 description 2
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
• 108010071690 Prealbumin Proteins 0.000 description 2
• 102000007584 Prealbumin Human genes 0.000 description 2
• 108010067787 Proteoglycans Proteins 0.000 description 2
• 102000016611 Proteoglycans Human genes 0.000 description 2
• 241000125945 Protoparvovirus Species 0.000 description 2
• 101000902592 Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1) DNA polymerase Proteins 0.000 description 2
• 101000854518 Rattus norvegicus Fractalkine Proteins 0.000 description 2
• 241000220317 Rosa Species 0.000 description 2
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
• 102100022760 Stress-70 protein, mitochondrial Human genes 0.000 description 2
• 108700026226 TATA Box Proteins 0.000 description 2
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
• RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 2
• IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
• 108020004566 Transfer RNA Proteins 0.000 description 2
• 238000010521 absorption reaction Methods 0.000 description 2
• 230000035508 accumulation Effects 0.000 description 2
• 238000009825 accumulation Methods 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine group Chemical group [C@@H]1([C@H](O)[C@H](O)[C@@H](CO)O1)N1C=NC=2C(N)=NC=NC12 OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 125000003545 alkoxy group Chemical group 0.000 description 2
• 125000005600 alkyl phosphonate group Chemical group 0.000 description 2
• 125000003277 amino group Chemical group 0.000 description 2
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
• 238000000137 annealing Methods 0.000 description 2
• 230000000844 anti-bacterial effect Effects 0.000 description 2
• 239000003429 antifungal agent Substances 0.000 description 2
• 229940121375 antifungal agent Drugs 0.000 description 2
• 230000000890 antigenic effect Effects 0.000 description 2
• 239000012736 aqueous medium Substances 0.000 description 2
• 230000003115 biocidal effect Effects 0.000 description 2
• 230000004071 biological effect Effects 0.000 description 2
• 229960002685 biotin Drugs 0.000 description 2
• 235000020958 biotin Nutrition 0.000 description 2
• 239000011616 biotin Substances 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 239000001110 calcium chloride Substances 0.000 description 2
• 235000011148 calcium chloride Nutrition 0.000 description 2
• 229910001628 calcium chloride Inorganic materials 0.000 description 2
• 244000309466 calf Species 0.000 description 2
• 229910052799 carbon Inorganic materials 0.000 description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 238000006555 catalytic reaction Methods 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 208000019065 cervical carcinoma Diseases 0.000 description 2
• 239000007795 chemical reaction product Substances 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• 235000012000 cholesterol Nutrition 0.000 description 2
• 210000000349 chromosome Anatomy 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 229960002424 collagenase Drugs 0.000 description 2
• 239000003184 complementary RNA Substances 0.000 description 2
• 230000009146 cooperative binding Effects 0.000 description 2
• CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• 238000010790 dilution Methods 0.000 description 2
• 239000012895 dilution Substances 0.000 description 2
• 208000037765 diseases and disorders Diseases 0.000 description 2
• 235000021186 dishes Nutrition 0.000 description 2
• 238000006073 displacement reaction Methods 0.000 description 2
• 238000009826 distribution Methods 0.000 description 2
• 238000012377 drug delivery Methods 0.000 description 2
• 238000004520 electroporation Methods 0.000 description 2
• 230000002708 enhancing effect Effects 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 238000001502 gel electrophoresis Methods 0.000 description 2
• 238000007429 general method Methods 0.000 description 2
• 229940096919 glycogen Drugs 0.000 description 2
• 230000012010 growth Effects 0.000 description 2
• 229920001519 homopolymer Polymers 0.000 description 2
• 230000002209 hydrophobic effect Effects 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 102000018358 immunoglobulin Human genes 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 239000000411 inducer Substances 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 230000003834 intracellular effect Effects 0.000 description 2
• 238000007912 intraperitoneal administration Methods 0.000 description 2
• 238000011901 isothermal amplification Methods 0.000 description 2
• 239000007951 isotonicity adjuster Substances 0.000 description 2
• 231100000518 lethal Toxicity 0.000 description 2
• 230000001665 lethal effect Effects 0.000 description 2
• 239000012139 lysis buffer Substances 0.000 description 2
• 229920002521 macromolecule Polymers 0.000 description 2
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
• 210000000865 mononuclear phagocyte system Anatomy 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• 201000006938 muscular dystrophy Diseases 0.000 description 2
• 239000002777 nucleoside Substances 0.000 description 2
• 125000003835 nucleoside group Chemical group 0.000 description 2
• 230000030648 nucleus localization Effects 0.000 description 2
• 229940049954 penicillin Drugs 0.000 description 2
• 210000001539 phagocyte Anatomy 0.000 description 2
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 239000002953 phosphate buffered saline Substances 0.000 description 2
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
• 150000008300 phosphoramidites Chemical class 0.000 description 2
• 229920002401 polyacrylamide Polymers 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• 238000001556 precipitation Methods 0.000 description 2
• 230000002035 prolonged effect Effects 0.000 description 2
• 230000000069 prophylactic effect Effects 0.000 description 2
• 238000011321 prophylaxis Methods 0.000 description 2
• XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 2
• 230000008439 repair process Effects 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 230000000717 retained effect Effects 0.000 description 2
• 230000035945 sensitivity Effects 0.000 description 2
• 238000002864 sequence alignment Methods 0.000 description 2
• 238000013207 serial dilution Methods 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
• 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
• 229940054269 sodium pyruvate Drugs 0.000 description 2
• 238000000527 sonication Methods 0.000 description 2
• 238000001179 sorption measurement Methods 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• 229960005322 streptomycin Drugs 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 150000008163 sugars Chemical class 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• 230000002194 synthesizing effect Effects 0.000 description 2
• 230000009897 systematic effect Effects 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• 230000009466 transformation Effects 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• 239000001226 triphosphate Substances 0.000 description 2
• 239000002691 unilamellar liposome Substances 0.000 description 2
• 238000011144 upstream manufacturing Methods 0.000 description 2
• 230000017613 viral reproduction Effects 0.000 description 2
• 238000012800 visualization Methods 0.000 description 2
• QGVLYPPODPLXMB-UBTYZVCOSA-N (1aR,1bS,4aR,7aS,7bS,8R,9R,9aS)-4a,7b,9,9a-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-5H-cyclopropa[3,4]benzo[1,2-e]azulen-5-one Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 QGVLYPPODPLXMB-UBTYZVCOSA-N 0.000 description 1
• UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 1
• BZSXEZOLBIJVQK-UHFFFAOYSA-N 2-methylsulfonylbenzoic acid Chemical compound CS(=O)(=O)C1=CC=CC=C1C(O)=O BZSXEZOLBIJVQK-UHFFFAOYSA-N 0.000 description 1
• 101710106459 29 kDa protein Proteins 0.000 description 1
• MXVJCCPMGYHBLH-UHFFFAOYSA-N 6-chloro-2-methoxy-n-pentylacridin-9-amine Chemical compound C1=C(OC)C=C2C(NCCCCC)=C(C=CC(Cl)=C3)C3=NC2=C1 MXVJCCPMGYHBLH-UHFFFAOYSA-N 0.000 description 1
• 108010088751 Albumins Proteins 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 208000000044 Amnesia Diseases 0.000 description 1
• 101100449539 Arabidopsis thaliana GRP17 gene Proteins 0.000 description 1
• 101100321720 Arabidopsis thaliana PP2AA1 gene Proteins 0.000 description 1
• 101100411820 Arabidopsis thaliana RBG7 gene Proteins 0.000 description 1
• 238000012935 Averaging Methods 0.000 description 1
• 241000711404 Avian avulavirus 1 Species 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 101000653197 Beet necrotic yellow vein virus (isolate Japan/S) Movement protein TGB3 Proteins 0.000 description 1
• DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
• 241000197194 Bulla Species 0.000 description 1
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
• GQUGNZGVBHJMRM-UHFFFAOYSA-N C1=C(Cl)C=CC2=CC3=C(OC(CCCN)C(O)(OC)P(=O)N(C(C)C)C(C)C)C(OC)=CC=C3N=C21 Chemical compound C1=C(Cl)C=CC2=CC3=C(OC(CCCN)C(O)(OC)P(=O)N(C(C)C)C(C)C)C(OC)=CC=C3N=C21 GQUGNZGVBHJMRM-UHFFFAOYSA-N 0.000 description 1
• VYJXBORORKHCDO-UHFFFAOYSA-N CC(C)N(C(C)C)P(C(C(CN)OC(C(C(C=C1)=NC2=C3)=CC2=CC=C3Cl)=C1OC)(O)OC)=O Chemical compound CC(C)N(C(C)C)P(C(C(CN)OC(C(C(C=C1)=NC2=C3)=CC2=CC=C3Cl)=C1OC)(O)OC)=O VYJXBORORKHCDO-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 101710163595 Chaperone protein DnaK Proteins 0.000 description 1
• 108020004635 Complementary DNA Proteins 0.000 description 1
• 108091035707 Consensus sequence Proteins 0.000 description 1
• MIKUYHXYGGJMLM-GIMIYPNGSA-N Crotonoside Natural products C1=NC2=C(N)NC(=O)N=C2N1[C@H]1O[C@@H](CO)[C@H](O)[C@@H]1O MIKUYHXYGGJMLM-GIMIYPNGSA-N 0.000 description 1
• 229920001651 Cyanoacrylate Polymers 0.000 description 1
• 229920000858 Cyclodextrin Polymers 0.000 description 1
• UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
• 102100030497 Cytochrome c Human genes 0.000 description 1
• 108010075031 Cytochromes c Proteins 0.000 description 1
• 108010017826 DNA Polymerase I Proteins 0.000 description 1
• 102000004594 DNA Polymerase I Human genes 0.000 description 1
• 108010076804 DNA Restriction Enzymes Proteins 0.000 description 1
• 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
• 238000001712 DNA sequencing Methods 0.000 description 1
• 206010011878 Deafness Diseases 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• 206010061818 Disease progression Diseases 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 102100031780 Endonuclease Human genes 0.000 description 1
• 102000004533 Endonucleases Human genes 0.000 description 1
• 108700041152 Endoplasmic Reticulum Chaperone BiP Proteins 0.000 description 1
• 102100021451 Endoplasmic reticulum chaperone BiP Human genes 0.000 description 1
• 102100039328 Endoplasmin Human genes 0.000 description 1
• 241001524679 Escherichia virus M13 Species 0.000 description 1
• 101150043759 FP gene Proteins 0.000 description 1
• 238000012413 Fluorescence activated cell sorting analysis Methods 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 241000287828 Gallus gallus Species 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
• 241000713813 Gibbon ape leukemia virus Species 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 229930186217 Glycolipid Natural products 0.000 description 1
• 108010062347 HLA-DQ Antigens Proteins 0.000 description 1
• 101150112743 HSPA5 gene Proteins 0.000 description 1
• 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 1
• 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 1
• 241000724709 Hepatitis delta virus Species 0.000 description 1
• 101710121996 Hexon protein p72 Proteins 0.000 description 1
• 108010033040 Histones Proteins 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 241000701024 Human betaherpesvirus 5 Species 0.000 description 1
• 241000725303 Human immunodeficiency virus Species 0.000 description 1
• 241000484121 Human parvovirus Species 0.000 description 1
• 241000883306 Huso huso Species 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
• 101150017040 I gene Proteins 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 108700002232 Immediate-Early Genes Proteins 0.000 description 1
• 229930010555 Inosine Natural products 0.000 description 1
• UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
• 108091092195 Intron Proteins 0.000 description 1
• LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
• 229930182816 L-glutamine Natural products 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• 101710128836 Large T antigen Proteins 0.000 description 1
• 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
• 240000006240 Linum usitatissimum Species 0.000 description 1
• 102000004895 Lipoproteins Human genes 0.000 description 1
• 108090001030 Lipoproteins Proteins 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 1
• 208000026139 Memory disease Diseases 0.000 description 1
• 102000003792 Metallothionein Human genes 0.000 description 1
• 108090000157 Metallothionein Proteins 0.000 description 1
• 101710201349 Metallothionein B Proteins 0.000 description 1
• 102100031347 Metallothionein-2 Human genes 0.000 description 1
• 101710094505 Metallothionein-2 Proteins 0.000 description 1
• 108060004795 Methyltransferase Proteins 0.000 description 1
• 208000023178 Musculoskeletal disease Diseases 0.000 description 1
• 108010069196 Neural Cell Adhesion Molecules Proteins 0.000 description 1
• 102000011830 Neural cell adhesion Human genes 0.000 description 1
• 108050002172 Neural cell adhesion Proteins 0.000 description 1
• 102100027347 Neural cell adhesion molecule 1 Human genes 0.000 description 1
• 101710163270 Nuclease Proteins 0.000 description 1
• 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
• 240000007817 Olea europaea Species 0.000 description 1
• BYLFVQBHSSVIAL-UHFFFAOYSA-N P.FP Chemical compound P.FP BYLFVQBHSSVIAL-UHFFFAOYSA-N 0.000 description 1
• 108010067372 Pancreatic elastase Proteins 0.000 description 1
• 102000016387 Pancreatic elastase Human genes 0.000 description 1
• 241001631646 Papillomaviridae Species 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 108091093037 Peptide nucleic acid Proteins 0.000 description 1
• 102000003992 Peroxidases Human genes 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 108010009460 RNA Polymerase II Proteins 0.000 description 1
• 102000009572 RNA Polymerase II Human genes 0.000 description 1
• 108010078067 RNA Polymerase III Proteins 0.000 description 1
• 102000014450 RNA Polymerase III Human genes 0.000 description 1
• 230000007022 RNA scission Effects 0.000 description 1
• 244000088415 Raphanus sativus Species 0.000 description 1
• 235000006140 Raphanus sativus var sativus Nutrition 0.000 description 1
• 101000868151 Rattus norvegicus Somatotropin Proteins 0.000 description 1
• 230000010799 Receptor Interactions Effects 0.000 description 1
• 108091027981 Response element Proteins 0.000 description 1
• 108091028664 Ribonucleotide Proteins 0.000 description 1
• 241000283984 Rodentia Species 0.000 description 1
• 241000714474 Rous sarcoma virus Species 0.000 description 1
• 101100111629 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) KAR2 gene Proteins 0.000 description 1
• 108020005543 Satellite RNA Proteins 0.000 description 1
• 241000710961 Semliki Forest virus Species 0.000 description 1
• 102000054727 Serum Amyloid A Human genes 0.000 description 1
• 108700028909 Serum Amyloid A Proteins 0.000 description 1
• 244000191761 Sida cordifolia Species 0.000 description 1
• 241000710960 Sindbis virus Species 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 101001086866 Sus scrofa Pulmonary surfactant-associated protein B Proteins 0.000 description 1
• 108091008874 T cell receptors Proteins 0.000 description 1
• 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
• 210000001744 T-lymphocyte Anatomy 0.000 description 1
• 101710137500 T7 RNA polymerase Proteins 0.000 description 1
• 108010006785 Taq Polymerase Proteins 0.000 description 1
• 108091036066 Three prime untranslated region Proteins 0.000 description 1
• AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
• 102000011923 Thyrotropin Human genes 0.000 description 1
• 108010061174 Thyrotropin Proteins 0.000 description 1
• 108700009124 Transcription Initiation Site Proteins 0.000 description 1
• 102000013394 Troponin I Human genes 0.000 description 1
• 108010065729 Troponin I Proteins 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
• 102100035071 Vimentin Human genes 0.000 description 1
• 108010065472 Vimentin Proteins 0.000 description 1
• 108020000999 Viral RNA Proteins 0.000 description 1
• 108070000030 Viral receptors Proteins 0.000 description 1
• 108091093126 WHP Posttrascriptional Response Element Proteins 0.000 description 1
• 235000010724 Wisteria floribunda Nutrition 0.000 description 1
• VRGWBRLULZUWAJ-XFFXIZSCSA-N [(2s)-2-[(1r,3z,5s,8z,12z,15s)-5,17-dihydroxy-4,8,12,15-tetramethyl-16-oxo-18-bicyclo[13.3.0]octadeca-3,8,12,17-tetraenyl]propyl] acetate Chemical compound C1\C=C(C)/CC\C=C(C)/CC[C@H](O)\C(C)=C/C[C@@H]2C([C@@H](COC(C)=O)C)=C(O)C(=O)[C@]21C VRGWBRLULZUWAJ-XFFXIZSCSA-N 0.000 description 1
• 239000003070 absorption delaying agent Substances 0.000 description 1
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
• 229960005305 adenosine Drugs 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 238000001042 affinity chromatography Methods 0.000 description 1
• 230000002776 aggregation Effects 0.000 description 1
• 238000004220 aggregation Methods 0.000 description 1
• 238000012867 alanine scanning Methods 0.000 description 1
• 125000000217 alkyl group Chemical group 0.000 description 1
• 230000000172 allergic effect Effects 0.000 description 1
• 239000012637 allosteric effector Substances 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 229940027998 antiseptic and disinfectant acridine derivative Drugs 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 230000003190 augmentative effect Effects 0.000 description 1
• 230000006472 autoimmune response Effects 0.000 description 1
• 230000005812 autoimmune toxicity Effects 0.000 description 1
• 208000022362 bacterial infectious disease Diseases 0.000 description 1
• 239000013602 bacteriophage vector Substances 0.000 description 1
• 230000037429 base substitution Effects 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
• 239000000227 bioadhesive Substances 0.000 description 1
• 230000008827 biological function Effects 0.000 description 1
• 239000012472 biological sample Substances 0.000 description 1
• 229960000074 biopharmaceutical Drugs 0.000 description 1
• 229920001222 biopolymer Polymers 0.000 description 1
• 208000002352 blister Diseases 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• 210000004899 c-terminal region Anatomy 0.000 description 1
• 238000010804 cDNA synthesis Methods 0.000 description 1
• AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 150000001720 carbohydrates Chemical class 0.000 description 1
• 235000014633 carbohydrates Nutrition 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 108020001778 catalytic domains Proteins 0.000 description 1
• 125000002091 cationic group Chemical class 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 230000004663 cell proliferation Effects 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• 230000017455 cell-cell adhesion Effects 0.000 description 1
• 230000033383 cell-cell recognition Effects 0.000 description 1
• 238000007385 chemical modification Methods 0.000 description 1
• 235000013330 chicken meat Nutrition 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• 230000004186 co-expression Effects 0.000 description 1
• 230000008045 co-localization Effects 0.000 description 1
• 239000011248 coating agent Substances 0.000 description 1
• 239000000084 colloidal system Substances 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 230000001609 comparable effect Effects 0.000 description 1
• 238000005094 computer simulation Methods 0.000 description 1
• 238000004624 confocal microscopy Methods 0.000 description 1
• 108091036078 conserved sequence Proteins 0.000 description 1
• 230000001276 controlling effect Effects 0.000 description 1
• 238000011443 conventional therapy Methods 0.000 description 1
• 229960003624 creatine Drugs 0.000 description 1
• 239000006046 creatine Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 210000004748 cultured cell Anatomy 0.000 description 1
• WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
• 229940097362 cyclodextrins Drugs 0.000 description 1
• 229960003067 cystine Drugs 0.000 description 1
• UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
• 230000009089 cytolysis Effects 0.000 description 1
• 210000000805 cytoplasm Anatomy 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 238000003745 diagnosis Methods 0.000 description 1
• 230000029087 digestion Effects 0.000 description 1
• UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
• 239000000539 dimer Substances 0.000 description 1
• 150000002016 disaccharides Chemical group 0.000 description 1
• 230000008034 disappearance Effects 0.000 description 1
• 230000005750 disease progression Effects 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• 229910000397 disodium phosphate Inorganic materials 0.000 description 1
• 235000019800 disodium phosphate Nutrition 0.000 description 1
• 238000010494 dissociation reaction Methods 0.000 description 1
• 230000005593 dissociations Effects 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 230000009881 electrostatic interaction Effects 0.000 description 1
• 238000005421 electrostatic potential Methods 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 238000005538 encapsulation Methods 0.000 description 1
• 230000012202 endocytosis Effects 0.000 description 1
• 210000003989 endothelium vascular Anatomy 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
• 229960005542 ethidium bromide Drugs 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 238000000684 flow cytometry Methods 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 238000007710 freezing Methods 0.000 description 1
• 230000008014 freezing Effects 0.000 description 1
• 230000005714 functional activity Effects 0.000 description 1
• VRGWBRLULZUWAJ-UHFFFAOYSA-N fusaproliferin Natural products C1C=C(C)CCC=C(C)CCC(O)C(C)=CCC2C(C(COC(C)=O)C)=C(O)C(=O)C21C VRGWBRLULZUWAJ-UHFFFAOYSA-N 0.000 description 1
• 108020001507 fusion proteins Proteins 0.000 description 1
• 102000037865 fusion proteins Human genes 0.000 description 1
• 238000004817 gas chromatography Methods 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 238000012252 genetic analysis Methods 0.000 description 1
• 238000010353 genetic engineering Methods 0.000 description 1
• 239000003862 glucocorticoid Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 108010017007 glucose-regulated proteins Proteins 0.000 description 1
• 150000004676 glycans Chemical class 0.000 description 1
• 230000002710 gonadal effect Effects 0.000 description 1
• 230000005484 gravity Effects 0.000 description 1
• 101150028578 grp78 gene Proteins 0.000 description 1
• PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
• 229940029575 guanosine Drugs 0.000 description 1
• 238000003306 harvesting Methods 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 238000003505 heat denaturation Methods 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 229910001385 heavy metal Inorganic materials 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 210000003494 hepatocyte Anatomy 0.000 description 1
• 238000004128 high performance liquid chromatography Methods 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 150000002430 hydrocarbons Chemical class 0.000 description 1
• 235000011167 hydrochloric acid Nutrition 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• 239000001257 hydrogen Substances 0.000 description 1
• 229910052739 hydrogen Inorganic materials 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 150000004679 hydroxides Chemical class 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 230000002163 immunogen Effects 0.000 description 1
• 230000005847 immunogenicity Effects 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 230000036512 infertility Effects 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 229960003786 inosine Drugs 0.000 description 1
• 238000009830 intercalation Methods 0.000 description 1
• 230000008611 intercellular interaction Effects 0.000 description 1
• 230000006525 intracellular process Effects 0.000 description 1
• 238000000185 intracerebroventricular administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 238000005342 ion exchange Methods 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 238000002372 labelling Methods 0.000 description 1
• 150000002605 large molecules Chemical class 0.000 description 1
• 238000011031 large-scale manufacturing process Methods 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 238000007834 ligase chain reaction Methods 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000006193 liquid solution Substances 0.000 description 1
• 239000006194 liquid suspension Substances 0.000 description 1
• 244000144972 livestock Species 0.000 description 1
• 239000012160 loading buffer Substances 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 206010025135 lupus erythematosus Diseases 0.000 description 1
• 210000005210 lymphoid organ Anatomy 0.000 description 1
• 239000006166 lysate Substances 0.000 description 1
• 108010026228 mRNA guanylyltransferase Proteins 0.000 description 1
• 210000002540 macrophage Anatomy 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 238000002826 magnetic-activated cell sorting Methods 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 238000013507 mapping Methods 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 230000035800 maturation Effects 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 230000006984 memory degeneration Effects 0.000 description 1
• 208000023060 memory loss Diseases 0.000 description 1
• YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
• 238000000520 microinjection Methods 0.000 description 1
• 238000000386 microscopy Methods 0.000 description 1
• 235000013336 milk Nutrition 0.000 description 1
• 239000008267 milk Substances 0.000 description 1
• 210000004080 milk Anatomy 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 239000002991 molded plastic Substances 0.000 description 1
• 238000001823 molecular biology technique Methods 0.000 description 1
• 238000003032 molecular docking Methods 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 239000000178 monomer Substances 0.000 description 1
• 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
• 230000003387 muscular Effects 0.000 description 1
• 239000003471 mutagenic agent Substances 0.000 description 1
• 101150008049 mx gene Proteins 0.000 description 1
• 230000009251 neurologic dysfunction Effects 0.000 description 1
• 208000015015 neurological dysfunction Diseases 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 210000000440 neutrophil Anatomy 0.000 description 1
• 229910052759 nickel Inorganic materials 0.000 description 1
• 229910052757 nitrogen Inorganic materials 0.000 description 1
• 230000009871 nonspecific binding Effects 0.000 description 1
• 230000005937 nuclear translocation Effects 0.000 description 1
• 239000002853 nucleic acid probe Substances 0.000 description 1
• 238000001668 nucleic acid synthesis Methods 0.000 description 1
• 150000003833 nucleoside derivatives Chemical class 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 235000019198 oils Nutrition 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 238000012856 packing Methods 0.000 description 1
• 238000004816 paper chromatography Methods 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 238000005192 partition Methods 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 108040007629 peroxidase activity proteins Proteins 0.000 description 1
• 235000020030 perry Nutrition 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 229960003742 phenol Drugs 0.000 description 1
• QGVLYPPODPLXMB-QXYKVGAMSA-N phorbol Natural products C[C@@H]1[C@@H](O)[C@]2(O)[C@H]([C@H]3C=C(CO)C[C@@]4(O)[C@H](C=C(C)C4=O)[C@@]13O)C2(C)C QGVLYPPODPLXMB-QXYKVGAMSA-N 0.000 description 1
• 150000004713 phosphodiesters Chemical group 0.000 description 1
• 235000011007 phosphoric acid Nutrition 0.000 description 1
• 150000003016 phosphoric acids Chemical class 0.000 description 1
• LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• 230000035479 physiological effects, processes and functions Effects 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 210000004180 plasmocyte Anatomy 0.000 description 1
• 238000003752 polymerase chain reaction Methods 0.000 description 1
• 230000000379 polymerizing effect Effects 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 0.000 description 1
• 239000011148 porous material Substances 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• 230000037452 priming Effects 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 229930185346 proliferin Natural products 0.000 description 1
• 238000001273 protein sequence alignment Methods 0.000 description 1
• 230000012743 protein tagging Effects 0.000 description 1
• 210000001938 protoplast Anatomy 0.000 description 1
• 239000002510 pyrogen Substances 0.000 description 1
• 239000013646 rAAV2 vector Substances 0.000 description 1
• 230000002285 radioactive effect Effects 0.000 description 1
• 230000003439 radiotherapeutic effect Effects 0.000 description 1
• 238000013322 recombinant adeno-associated virus production system Methods 0.000 description 1
• 238000003259 recombinant expression Methods 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000003252 repetitive effect Effects 0.000 description 1
• 230000002207 retinal effect Effects 0.000 description 1
• 230000001177 retroviral effect Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 239000002336 ribonucleotide Substances 0.000 description 1
• 125000002652 ribonucleotide group Chemical group 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 125000005629 sialic acid group Chemical group 0.000 description 1
• 230000037432 silent mutation Effects 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 235000012239 silicon dioxide Nutrition 0.000 description 1
• 150000003384 small molecules Chemical class 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 230000009870 specific binding Effects 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 108091007196 stromelysin Proteins 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 230000009469 supplementation Effects 0.000 description 1
• 230000008093 supporting effect Effects 0.000 description 1
• 238000007910 systemic administration Methods 0.000 description 1
• 238000012385 systemic delivery Methods 0.000 description 1
• 229940037128 systemic glucocorticoids Drugs 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 238000010257 thawing Methods 0.000 description 1
• 229940126585 therapeutic drug Drugs 0.000 description 1
• RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
• 229940033663 thimerosal Drugs 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• WZMPOCLULGAHJR-UHFFFAOYSA-N thiophen-2-ol Chemical compound OC1=CC=CS1 WZMPOCLULGAHJR-UHFFFAOYSA-N 0.000 description 1
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
• 229940104230 thymidine Drugs 0.000 description 1
• 239000005495 thyroid hormone Substances 0.000 description 1
• 229940036555 thyroid hormone Drugs 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000005030 transcription termination Effects 0.000 description 1
• 230000002463 transducing effect Effects 0.000 description 1
• 238000003151 transfection method Methods 0.000 description 1
• 238000006276 transfer reaction Methods 0.000 description 1
• 230000005945 translocation Effects 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• 235000011178 triphosphate Nutrition 0.000 description 1
• 125000002264 triphosphate group Chemical class [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 1
• 239000011882 ultra-fine particle Substances 0.000 description 1
• 238000002604 ultrasonography Methods 0.000 description 1
• 241001430294 unidentified retrovirus Species 0.000 description 1
• 238000001291 vacuum drying Methods 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 108700026220 vif Genes Proteins 0.000 description 1
• 210000005048 vimentin Anatomy 0.000 description 1
• 230000007502 viral entry Effects 0.000 description 1
• 230000029812 viral genome replication Effects 0.000 description 1
• 230000000007 visual effect Effects 0.000 description 1
• 238000007794 visualization technique Methods 0.000 description 1
• 238000005406 washing Methods 0.000 description 1