JP2017510264A - 昆虫細胞で産生される、さらに改善されたaavベクター - Google Patents
昆虫細胞で産生される、さらに改善されたaavベクター Download PDFInfo
- Publication number
- JP2017510264A JP2017510264A JP2016555770A JP2016555770A JP2017510264A JP 2017510264 A JP2017510264 A JP 2017510264A JP 2016555770 A JP2016555770 A JP 2016555770A JP 2016555770 A JP2016555770 A JP 2016555770A JP 2017510264 A JP2017510264 A JP 2017510264A
- Authority
- JP
- Japan
- Prior art keywords
- aav
- nucleotide sequence
- sequence
- amino acid
- expression
- Prior art date
- 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.)
- Granted
Links
- 241000238631 Hexapoda Species 0.000 title claims abstract description 124
- 239000013607 AAV vector Substances 0.000 title description 11
- 230000001976 improved effect Effects 0.000 title description 11
- 239000002773 nucleotide Substances 0.000 claims abstract description 164
- 125000003729 nucleotide group Chemical group 0.000 claims abstract description 164
- 230000014509 gene expression Effects 0.000 claims abstract description 122
- 239000013598 vector Substances 0.000 claims abstract description 116
- 108090000565 Capsid Proteins Proteins 0.000 claims abstract description 115
- 102100023321 Ceruloplasmin Human genes 0.000 claims abstract description 113
- 108091081024 Start codon Proteins 0.000 claims abstract description 79
- 238000004519 manufacturing process Methods 0.000 claims abstract description 60
- 108020004705 Codon Proteins 0.000 claims abstract description 58
- 125000000539 amino acid group Chemical group 0.000 claims abstract description 55
- 230000014621 translational initiation Effects 0.000 claims abstract description 48
- 108091026890 Coding region Proteins 0.000 claims abstract description 32
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 31
- 101100524324 Adeno-associated virus 2 (isolate Srivastava/1982) Rep78 gene Proteins 0.000 claims abstract description 30
- 101100524319 Adeno-associated virus 2 (isolate Srivastava/1982) Rep52 gene Proteins 0.000 claims abstract description 25
- 235000004279 alanine Nutrition 0.000 claims abstract description 23
- 241000702421 Dependoparvovirus Species 0.000 claims abstract description 20
- 101100524321 Adeno-associated virus 2 (isolate Srivastava/1982) Rep68 gene Proteins 0.000 claims abstract description 19
- 239000004471 Glycine Substances 0.000 claims abstract description 16
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims abstract description 16
- 235000014393 valine Nutrition 0.000 claims abstract description 16
- 239000004474 valine Substances 0.000 claims abstract description 16
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims abstract description 15
- 101100524317 Adeno-associated virus 2 (isolate Srivastava/1982) Rep40 gene Proteins 0.000 claims abstract description 14
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims abstract description 14
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims abstract description 14
- 150000001413 amino acids Chemical group 0.000 claims abstract description 13
- 235000013922 glutamic acid Nutrition 0.000 claims abstract description 13
- 239000004220 glutamic acid Substances 0.000 claims abstract description 13
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims abstract description 12
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims abstract description 12
- 235000003704 aspartic acid Nutrition 0.000 claims abstract description 12
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims abstract description 12
- 210000004027 cell Anatomy 0.000 claims description 169
- 108090000623 proteins and genes Proteins 0.000 claims description 87
- 150000007523 nucleic acids Chemical class 0.000 claims description 61
- 241001634120 Adeno-associated virus - 5 Species 0.000 claims description 55
- 108020004707 nucleic acids Proteins 0.000 claims description 55
- 102000039446 nucleic acids Human genes 0.000 claims description 55
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 40
- 210000002845 virion Anatomy 0.000 claims description 31
- 108700026244 Open Reading Frames Proteins 0.000 claims description 27
- 210000004962 mammalian cell Anatomy 0.000 claims description 27
- 241000701447 unidentified baculovirus Species 0.000 claims description 27
- 241001164825 Adeno-associated virus - 8 Species 0.000 claims description 8
- 102100022641 Coagulation factor IX Human genes 0.000 claims description 8
- 108010076282 Factor IX Proteins 0.000 claims description 8
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims description 8
- 229960004222 factor ix Drugs 0.000 claims description 7
- 108010054218 Factor VIII Proteins 0.000 claims description 6
- 102000001690 Factor VIII Human genes 0.000 claims description 6
- 241000649044 Adeno-associated virus 9 Species 0.000 claims description 3
- 101100507655 Canis lupus familiaris HSPA1 gene Proteins 0.000 claims description 3
- 101100339887 Drosophila melanogaster Hsp27 gene Proteins 0.000 claims description 3
- 101150096895 HSPB1 gene Proteins 0.000 claims description 3
- 238000012258 culturing Methods 0.000 claims description 3
- 210000000234 capsid Anatomy 0.000 abstract description 54
- 238000013519 translation Methods 0.000 abstract description 29
- 239000013603 viral vector Substances 0.000 abstract description 5
- 230000003612 virological effect Effects 0.000 abstract description 5
- 101710132601 Capsid protein Proteins 0.000 description 134
- 101710197658 Capsid protein VP1 Proteins 0.000 description 134
- 101710118046 RNA-directed RNA polymerase Proteins 0.000 description 134
- 101710108545 Viral protein 1 Proteins 0.000 description 134
- 101710081079 Minor spike protein H Proteins 0.000 description 68
- 101000805768 Banna virus (strain Indonesia/JKT-6423/1980) mRNA (guanine-N(7))-methyltransferase Proteins 0.000 description 60
- 101000686790 Chaetoceros protobacilladnavirus 2 Replication-associated protein Proteins 0.000 description 60
- 101000864475 Chlamydia phage 1 Internal scaffolding protein VP3 Proteins 0.000 description 60
- 101000803553 Eumenes pomiformis Venom peptide 3 Proteins 0.000 description 60
- 101000583961 Halorubrum pleomorphic virus 1 Matrix protein Proteins 0.000 description 60
- 108010067390 Viral Proteins Proteins 0.000 description 35
- 239000000047 product Substances 0.000 description 34
- 239000002245 particle Substances 0.000 description 32
- 102000004169 proteins and genes Human genes 0.000 description 31
- 230000014616 translation Effects 0.000 description 31
- 235000018102 proteins Nutrition 0.000 description 27
- 238000000034 method Methods 0.000 description 20
- 230000004048 modification Effects 0.000 description 18
- 238000012986 modification Methods 0.000 description 18
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 17
- 241000125945 Protoparvovirus Species 0.000 description 17
- 230000010354 integration Effects 0.000 description 17
- 241000700605 Viruses Species 0.000 description 16
- 230000000694 effects Effects 0.000 description 16
- 238000001727 in vivo Methods 0.000 description 16
- 241000699670 Mus sp. Species 0.000 description 15
- 238000000338 in vitro Methods 0.000 description 15
- 208000015181 infectious disease Diseases 0.000 description 14
- 125000003275 alpha amino acid group Chemical group 0.000 description 13
- 230000000875 corresponding effect Effects 0.000 description 12
- 238000011144 upstream manufacturing Methods 0.000 description 12
- 235000001014 amino acid Nutrition 0.000 description 11
- 238000010348 incorporation Methods 0.000 description 11
- 230000007246 mechanism Effects 0.000 description 11
- 108700019146 Transgenes Proteins 0.000 description 10
- 229940024606 amino acid Drugs 0.000 description 10
- 108020004999 messenger RNA Proteins 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 102100026735 Coagulation factor VIII Human genes 0.000 description 9
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 230000010076 replication Effects 0.000 description 9
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 8
- 108700008625 Reporter Genes Proteins 0.000 description 8
- 238000013320 baculovirus expression vector system Methods 0.000 description 8
- 230000027455 binding Effects 0.000 description 8
- 238000009396 hybridization Methods 0.000 description 8
- 239000003999 initiator Substances 0.000 description 8
- 229920001184 polypeptide Polymers 0.000 description 8
- 102000004196 processed proteins & peptides Human genes 0.000 description 8
- 238000013518 transcription Methods 0.000 description 8
- 230000035897 transcription Effects 0.000 description 8
- 230000002068 genetic effect Effects 0.000 description 7
- 239000013608 rAAV vector Substances 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 239000004055 small Interfering RNA Substances 0.000 description 7
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 6
- 108091035707 Consensus sequence Proteins 0.000 description 6
- 108010013563 Lipoprotein Lipase Proteins 0.000 description 6
- 102100022119 Lipoprotein lipase Human genes 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 238000001190 Q-PCR Methods 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 238000013461 design Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 238000003780 insertion Methods 0.000 description 6
- 230000037431 insertion Effects 0.000 description 6
- 241000202702 Adeno-associated virus - 3 Species 0.000 description 5
- 101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 5
- 102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 5
- 108020004459 Small interfering RNA Proteins 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 238000001415 gene therapy Methods 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000002458 infectious effect Effects 0.000 description 5
- 238000009126 molecular therapy Methods 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 241000701945 Parvoviridae Species 0.000 description 4
- 238000007792 addition Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 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 description 4
- 239000003550 marker Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 238000004806 packaging method and process Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000013646 rAAV2 vector Substances 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 238000010361 transduction Methods 0.000 description 4
- 230000026683 transduction Effects 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- 241001164823 Adeno-associated virus - 7 Species 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- 208000003322 Coinfection Diseases 0.000 description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Chemical group CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
- 101710182846 Polyhedrin Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000001962 electrophoresis Methods 0.000 description 3
- 229960000301 factor viii Drugs 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 210000003705 ribosome Anatomy 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 241000300529 Adeno-associated virus 13 Species 0.000 description 2
- 102000005666 Apolipoprotein A-I Human genes 0.000 description 2
- 108010059886 Apolipoprotein A-I Proteins 0.000 description 2
- 101150044789 Cap gene Proteins 0.000 description 2
- 108700010070 Codon Usage Proteins 0.000 description 2
- 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 2
- 102000001039 Dystrophin Human genes 0.000 description 2
- 108010069091 Dystrophin Proteins 0.000 description 2
- 108010092408 Eosinophil Peroxidase Proteins 0.000 description 2
- 102100028471 Eosinophil peroxidase Human genes 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 102100027581 Forkhead box protein P3 Human genes 0.000 description 2
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 2
- 108091006109 GTPases Proteins 0.000 description 2
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 description 2
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000861452 Homo sapiens Forkhead box protein P3 Proteins 0.000 description 2
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 2
- 101000959820 Homo sapiens Interferon alpha-1/13 Proteins 0.000 description 2
- 101001067140 Homo sapiens Porphobilinogen deaminase Proteins 0.000 description 2
- 101000629622 Homo sapiens Serine-pyruvate aminotransferase Proteins 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 2
- 102100040019 Interferon alpha-1/13 Human genes 0.000 description 2
- 102000003814 Interleukin-10 Human genes 0.000 description 2
- 108090000174 Interleukin-10 Proteins 0.000 description 2
- 108010063738 Interleukins Proteins 0.000 description 2
- 102000015696 Interleukins Human genes 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical group CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical group C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
- 101001055320 Myxine glutinosa Insulin-like growth factor Proteins 0.000 description 2
- 102100034391 Porphobilinogen deaminase Human genes 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 206010038910 Retinitis Diseases 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- 102100026842 Serine-pyruvate aminotransferase Human genes 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 108091027967 Small hairpin RNA Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Chemical group CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
- 239000004473 Threonine Chemical group 0.000 description 2
- 108010022394 Threonine synthase Proteins 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- 108700009124 Transcription Initiation Site Proteins 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 2
- XCCTYIAWTASOJW-XVFCMESISA-N Uridine-5'-Diphosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 XCCTYIAWTASOJW-XVFCMESISA-N 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 238000003149 assay kit Methods 0.000 description 2
- OWMVSZAMULFTJU-UHFFFAOYSA-N bis-tris Chemical compound OCCN(CCO)C(CO)(CO)CO OWMVSZAMULFTJU-UHFFFAOYSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 230000005101 cell tropism Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000001627 detrimental effect Effects 0.000 description 2
- 102000004419 dihydrofolate reductase Human genes 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000009368 gene silencing by RNA Effects 0.000 description 2
- 108091006104 gene-regulatory proteins Proteins 0.000 description 2
- 102000034356 gene-regulatory proteins Human genes 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 229940047122 interleukins Drugs 0.000 description 2
- 230000010189 intracellular transport Effects 0.000 description 2
- 102000008371 intracellularly ATP-gated chloride channel activity proteins Human genes 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 231100000219 mutagenic Toxicity 0.000 description 2
- 230000003505 mutagenic effect Effects 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 229920002401 polyacrylamide Polymers 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 239000010979 ruby Substances 0.000 description 2
- 229910001750 ruby Inorganic materials 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 230000009261 transgenic effect Effects 0.000 description 2
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- 101150084750 1 gene Proteins 0.000 description 1
- 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 1
- 241000649045 Adeno-associated virus 10 Species 0.000 description 1
- 241000649046 Adeno-associated virus 11 Species 0.000 description 1
- 241000649047 Adeno-associated virus 12 Species 0.000 description 1
- 241000425548 Adeno-associated virus 3A Species 0.000 description 1
- 241000958487 Adeno-associated virus 3B Species 0.000 description 1
- 241000256173 Aedes albopictus Species 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 102100022712 Alpha-1-antitrypsin Human genes 0.000 description 1
- 235000002198 Annona diversifolia Nutrition 0.000 description 1
- 102100029470 Apolipoprotein E Human genes 0.000 description 1
- 101710095339 Apolipoprotein E Proteins 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- 241001390356 Bovine adeno-associated virus Species 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 108010080611 Cytosine Deaminase Proteins 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 241000121256 Densovirinae Species 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 241000255925 Diptera Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 101001091269 Escherichia coli Hygromycin-B 4-O-kinase Proteins 0.000 description 1
- 241000206602 Eukaryota Species 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 102000016354 Glucuronosyltransferase Human genes 0.000 description 1
- 108010092364 Glucuronosyltransferase Proteins 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-UHFFFAOYSA-N 0.000 description 1
- 108020005350 Initiator Codon Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 108010025815 Kanamycin Kinase Proteins 0.000 description 1
- 241000242362 Kordia Species 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical group CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 241000282838 Lama Species 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108091081548 Palindromic sequence Proteins 0.000 description 1
- 241000121250 Parvovirinae Species 0.000 description 1
- 108010064785 Phospholipases Proteins 0.000 description 1
- 102000015439 Phospholipases Human genes 0.000 description 1
- 241000490567 Pinctada Species 0.000 description 1
- 108010076039 Polyproteins Proteins 0.000 description 1
- WDVSHHCDHLJJJR-UHFFFAOYSA-N Proflavine Chemical compound C1=CC(N)=CC2=NC3=CC(N)=CC=C3C=C21 WDVSHHCDHLJJJR-UHFFFAOYSA-N 0.000 description 1
- 101710150114 Protein rep Proteins 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 108020005067 RNA Splice Sites Proteins 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 108020005091 Replication Origin Proteins 0.000 description 1
- 101710152114 Replication protein Proteins 0.000 description 1
- 102000009661 Repressor Proteins Human genes 0.000 description 1
- 108010034634 Repressor Proteins Proteins 0.000 description 1
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 108010034546 Serratia marcescens nuclease Proteins 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 0.000 description 1
- 101001091268 Streptomyces hygroscopicus Hygromycin-B 7''-O-kinase Proteins 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 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
- 102000002248 Thyroxine-Binding Globulin Human genes 0.000 description 1
- 108010000259 Thyroxine-Binding Globulin Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 108091006088 activator proteins Proteins 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 238000001261 affinity purification Methods 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
- 102000006646 aminoglycoside phosphotransferase Human genes 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- VJBCNMFKFZIXHC-UHFFFAOYSA-N azanium;2-(4-methyl-5-oxo-4-propan-2-yl-1h-imidazol-2-yl)quinoline-3-carboxylate Chemical compound N.N1C(=O)C(C(C)C)(C)N=C1C1=NC2=CC=CC=C2C=C1C(O)=O VJBCNMFKFZIXHC-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 230000000531 effect on virus Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000017188 evasion or tolerance of host immune response Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 1
- 229960002963 ganciclovir Drugs 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 1
- 229940097277 hygromycin b Drugs 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 108010026228 mRNA guanylyltransferase Proteins 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000007479 molecular analysis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 208000014500 neuronal tumor Diseases 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 101150066583 rep gene Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 230000024275 uncoating of virus Effects 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/14011—Baculoviridae
- C12N2710/14041—Use of virus, viral particle or viral elements as a vector
- C12N2710/14043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vectore
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14121—Viruses as such, e.g. new isolates, mutants or their genomic sequences
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14151—Methods of production or purification of viral material
- C12N2750/14152—Methods of production or purification of viral material relating to complementing cells and packaging systems for producing virus or viral particles
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2799/00—Uses of viruses
- C12N2799/02—Uses of viruses as vector
- C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
- C12N2799/026—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a baculovirus
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
(i)CTG、ACG、TTG、及びGTGからなる群から選択される、次善の翻訳開始コドンである第1のコドンと、
(ii)アラニン、グリシン、バリン、アスパラギン酸、及びグルタミン酸からなる群から選択されるアミノ酸残基をコードする第2のコドンと、
(iii)任意選択で、第2のコドンに続く、さらなるアミノ酸残基をコードする1又は複数のコドンと、
(iv)VP1翻訳開始コドンだけを欠く、アデノ随伴ウイルス(AAV)カプシドタンパク質をコードする配列と
を含むか又はこれらからなる、
核酸分子に関する。
(i)翻訳開始コドン、好ましくは、CTG、ACG、TTG、及びGTGからなる群から選択される次善の翻訳開始コドンによりコードされる、第1のアミノ酸残基と、
(ii)アラニン、グリシン、バリン、アスパラギン酸、及びグルタミン酸からなる群から選択される第2のアミノ酸残基と、
(iii)任意選択で、第2のアミノ酸残基に続く、1又は複数のさらなるアミノ酸残基と、
(iv)VP1翻訳開始コドンによりコードされるアミノ酸残基だけを欠く、AAV VP1カプシドタンパク質のアミノ酸配列と
を含むか又はこれらからなる、AAVビリオンに関する。
本明細書で使用される「作動可能に連結された」という用語は、ポリヌクレオチド(又はポリペプチド)エレメントの、機能的関係における連結を指す。核酸は、それが別の核酸配列と機能的関係に置かれている場合、「作動可能に連結されている」。例えば、転写調節配列は、それがコード配列の転写に影響を及ぼす場合、コード配列に作動可能に連結されている。「作動可能に連結された」とは、連結されるDNA配列が、連続配列であることが典型的であり、2つのタンパク質コード領域を接合することが必要な場合、連続配列であり、リーディングフレームにあることを意味する。
発明の詳細な説明
(i)CTG、ACG、TTG、及びGTGからなる群から選択される、次善の翻訳開始コドンである第1のコドンと、
(ii)アラニン、グリシン、バリン、アスパラギン酸、及びグルタミン酸からなる群から選択される第2のコドンと、
(iii)任意選択で、第2のコドンに続く、さらなるアミノ酸残基の1又は複数のコドンと、
(iv)VP1翻訳開始コドンを欠き、好ましくは、VP1翻訳開始コドンだけを欠き、又は、代替的に言えば、VP1翻訳開始コドンを欠くにすぎない、AAVカプシドタンパク質をコードする配列と
を含むか又はこれらからなる、核酸分子に関する。
(i)翻訳開始コドン、好ましくは、CTG、ACG、TTG、及びGTGからなる群から選択される次善の翻訳開始コドンによりコードされる、第1のアミノ酸残基と、
(ii)アラニン、グリシン、バリン、アスパラギン酸、及びグルタミン酸からなる群から選択される第2のアミノ酸残基と、
(iii)任意選択で、第2のアミノ酸残基に続く、1又は複数のさらなるアミノ酸残基と、
(iv)VP1翻訳開始コドンによりコードされるアミノ酸残基を欠き、好ましくは、VP1翻訳開始コドンによりコードされるアミノ酸残基だけを欠き、又は、代替的に言えば、VP1翻訳開始コドンによりコードされるアミノ酸残基を欠くにすぎない、AAV VP1カプシドタンパク質のアミノ酸配列と
を含むか又はこれらからなることが好ましい。
rAAVを産生させるための初期バキュロウイルス系は、Urabeら(Urabeら[2002]、Human Gene Therapy、13(16):1935〜1943)により記載され、3つのバキュロウイルス、すなわち、Bac−Rep、Bac−cap、及びBac−vecからなり、これらの昆虫細胞、例えば、SF9細胞への共感染は、rAAVの産生を結果としてもたらした。このような産生されたrAAVの特性、すなわち、効力を含む物理的特徴及び分子的特徴は、哺乳動物細胞で産生されたrAAVとあまり異ならなかった(Urabe[2002]、前出)。昆虫細胞のrAAVベクターの効率的な産生を達成するためには、工程に必要とされるAAVタンパク質を、適切なレベルで発現させなければならなかった。これは、多数のRepタンパク質及びCapタンパク質をコードするオペロンの適合を要求した。野生型AAVは、大型のRep78及び小型のRep52を、それぞれ、2つの顕著に異なるプロモーターであるp5及びp19から発現させ、2つのメッセンジャーのスプライシングの結果として、Rep68変異体及びRep52変異体の産生をもたらす。このオペロンの組織化は、限定的なRep78の発現と、比較的高量のRep52の発現とを結果としてもたらす。Rep78のRep52に対する比の小ささを模倣するために、Urabeらは、Rep78の発現は、即初期1遺伝子(ΔIE−1)の、部分的に欠失させたプロモーターにより駆動する一方で、Rep52の発現は、強力なポリヘドリンプロモーター(polh)により制御する、DNAカセットを構築した。昆虫細胞では、大型のRep及び小型のRepのスプライシングされた変異体が観察されなかったが、これは、哺乳動物細胞と昆虫細胞とのスプライシング工程の差違と関連する可能性が高い。克服すべき別の技術的課題は、3つの主要なウイルスタンパク質(VP)の発現に関連していた。野生型AAVは、VP1、VP2、及びVP3を、p40プロモーターから発現させる。生じるメッセンジャーRNAは、2つの分子種へとスプライシングされる:1つの分子種が、VP1発現の一因となるのに対し、第2の分子種は、タンパク質が、場合によって、リボソーム複合体により看過される非カノニカルの始点、すなわち、ACGから開始される「漏出性リボソーム走査機構」を介して、VP2及びVP3の両方を発現させるが、このとき、リボソーム複合体は、それが、VP3のカノニカルの始点を見出すまで、さらに前進する。脊椎動物細胞と昆虫細胞との、スプライシング機構の差違のために、上記で記載された機構は、昆虫細胞では、適正なカプシドの産生を結果としてもたらさなかった。Urabeらは、VP1の翻訳始点を、ACGへと変化させ、VP1に先行する9ヌクレオチドからなる開始コンテキストを、VP2に先行するヌクレオチドへと変化させるような形で、VP2に見出される修飾と類似する、VP1の翻訳始点の修飾を導入することを決定した。これらの遺伝子変化は、単一のポリシストロニックのmRNAに由来するカプシドへと適正にアセンブルされうる、3つのVPの、正確な当量比での発現を結果としてもたらした。他方で、導入遺伝子カセットは、哺乳動物ベースの系についてかつて記載されたカセットと類似し、複製及びパッケージングに要求される、唯一のイントランスのエレメントとしてのITRに挟まれた。
2.方法
2.1.rAAV5ベクターの産生
2.2.rAAV5ベクターの精製
2.4.in vitroにおける効力
2.5.in vivoにおける効力
3.結果
3.1.BEVSでのrAAV5の産生
3.3.VP3の過剰発現は、BEVSの真性5型AAV突然変異体の低効力の一因である
3.4.昆虫細胞により産生される純種のAAV5(765)は、in vivoにおいて、キメラ2/5型突然変異体より優れた効能を示す
4.考察
Claims (16)
- オープンリーディングフレームを含むヌクレオチド配列を有し、前記リーディングフレームが、5’から3’の順序で
(i)CTG、ACG、TTG、及びGTGからなる群から選択される、次善の翻訳開始コドンである第1のコドンと、
(ii)アラニン、グリシン、バリン、アスパラギン酸、及びグルタミン酸からなる群から選択されるアミノ酸残基をコードする第2のコドンと、
(iii)任意選択で、前記第2のコドンに続く、さらなるアミノ酸残基をコードする1又は複数のコドンと、
(iv)VP1翻訳開始コドンだけを欠く、アデノ随伴ウイルス(AAV)カプシドタンパク質をコードする配列と
を含む、核酸分子。 - 前記AAVカプシドタンパク質が、AAV血清型5、AAV血清型8、又はAAV血清型9カプシドタンパク質であり、好ましくは、前記カプシドタンパク質が、配列番号22、28、30、71、及び73からなる群から選択されるアミノ酸配列を有する、請求項1に記載の核酸分子。
- 前記第2のコドンが、アラニンをコードする、請求項1又は請求項2に記載の核酸分子。
- 前記第2のコドンが、GCT、GCC、GCA、GCG、及びGGUからなる群から選択され、好ましくは、前記コドンが、GCTである、請求項1又は請求項2に記載の核酸分子。
- 請求項1〜4のいずれか一項に記載の核酸分子を含み、前記アデノ随伴ウイルス(AAV)カプシドタンパク質をコードする前記リーディングフレームの前記ヌクレオチド配列が、昆虫細胞での発現用の発現制御配列に作動可能に連結されている、核酸構築物。
- 前記リーディングフレームの前記ヌクレオチド配列が、ポリヘドロンプロモーター、p10プロモーター、4×Hsp27 EcRE+最小Hsp70プロモーター、デルタE1プロモーター、E1プロモーターからなる群から選択されるプロモーターに作動可能に連結されている、請求項5に記載の核酸構築物。
- 昆虫適合性ベクター、好ましくは、バキュロウイルスベクターである、請求項5又は請求項6に記載の核酸構築物。
- 前記核酸分子が、配列番号51、69、42、47、48、及び50、好ましくは、配列番号51からなる群から選択されるオープンリーディングフレームを含む、請求項5〜7のいずれか一項に記載の核酸構築物。
- 請求項5〜8のいずれか一項に記載の核酸構築物を含む昆虫細胞。
- (a)少なくとも1つのAAV逆位末端反復配列(ITR)のヌクレオチド配列を含む第2のヌクレオチド配列と、
(b)昆虫細胞での発現用の発現制御配列に作動可能に連結されたRep78又はRep68コード配列を含む第3のヌクレオチド配列と、
(c)任意選択で、昆虫細胞での発現用の発現制御配列に作動可能に連結されたRep52又はRep40コード配列を含む第4のヌクレオチド配列と
をさらに含む、請求項9に記載の昆虫細胞。 - (a)請求項10の(b)及び(c)に記載の第3及び第4のヌクレオチド配列をさらに含む、請求項5〜8のいずれか一項に記載の第1の核酸構築物と、
(b)請求項10の(a)に記載の第2のヌクレオチド配列を含み、好ましくは、昆虫細胞適合性ベクター、より好ましくは、バキュロウイルスベクターである、第2の核酸構築物と
を含む、請求項10に記載の昆虫細胞。 - 前記第2のヌクレオチド配列が、目的の遺伝子産物をコードする少なくとも1つのヌクレオチド配列(哺乳動物細胞で発現させるための)をさらに含み、目的の遺伝子産物をコードする前記少なくとも1つのヌクレオチド配列が、前記昆虫細胞で産生されるAAV血清型5のゲノムへと組み込まれ、好ましくは、前記第2のヌクレオチド配列が、2つのAAV ITRヌクレオチド配列を含み、目的の遺伝子産物をコードする前記少なくとも1つのヌクレオチド配列が、前記2つのAAV ITRヌクレオチド配列の間に配置されている、請求項10〜11のいずれか一項に記載の昆虫細胞。
- 前記第1のヌクレオチド配列と、第2のヌクレオチド配列と、第3のヌクレオチド配列と、任意選択で、第4のヌクレオチド配列とが、前記昆虫細胞のゲノムに安定的に組み込まれている、請求項10に記載の昆虫細胞。
- ゲノムに、目的の遺伝子産物をコードする少なくとも1つのヌクレオチド配列を含み、前記少なくとも1つのヌクレオチド配列が、天然のAAVヌクレオチド配列ではなく、AAV VP1カプシドタンパク質が、N末端からC末端へと、
(i)翻訳開始コドン、好ましくは、CTG、ACG、TTG、及びGTGからなる群から選択される次善の翻訳開始コドンによりコードされる第1のアミノ酸残基と、
(ii)アラニン、グリシン、バリン、アスパラギン酸、及びグルタミン酸からなる群から選択される第2のアミノ酸残基と、
(iii)任意選択で、前記第2のアミノ酸残基に続く、1又は複数のさらなるアミノ酸残基と、
(iv)前記VP1翻訳開始コドンによりコードされる前記アミノ酸残基だけを欠く、前記AAV VP1カプシドタンパク質のアミノ酸配列と
を含む、AAVビリオン。 - AAVを昆虫細胞で産生させるための方法であって、(a)請求項9〜13のいずれか一項に記載の昆虫細胞を、AAVが産生されるような条件下で培養するステップと、任意選択で、(b)前記AAVを回収するステップとを含む方法。
- 前記目的の遺伝子産物が、第IX因子又は第VIII因子タンパク質をコードする、請求項14に記載のAAVビリオン。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP14158610.7 | 2014-03-10 | ||
EP14158610 | 2014-03-10 | ||
PCT/NL2015/050149 WO2015137802A1 (en) | 2014-03-10 | 2015-03-10 | Further improved aav vectors produced in insect cells |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020000121A Division JP2020062045A (ja) | 2014-03-10 | 2020-01-06 | 昆虫細胞で産生される、さらに改善されたaavベクター |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017510264A true JP2017510264A (ja) | 2017-04-13 |
JP6683397B2 JP6683397B2 (ja) | 2020-04-22 |
Family
ID=50238253
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016555770A Active JP6683397B2 (ja) | 2014-03-10 | 2015-03-10 | 昆虫細胞で産生される、さらに改善されたaavベクター |
JP2020000121A Pending JP2020062045A (ja) | 2014-03-10 | 2020-01-06 | 昆虫細胞で産生される、さらに改善されたaavベクター |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020000121A Pending JP2020062045A (ja) | 2014-03-10 | 2020-01-06 | 昆虫細胞で産生される、さらに改善されたaavベクター |
Country Status (17)
Country | Link |
---|---|
US (2) | US10837027B2 (ja) |
EP (1) | EP3117005B1 (ja) |
JP (2) | JP6683397B2 (ja) |
KR (1) | KR102572449B1 (ja) |
CN (1) | CN106459984B (ja) |
AU (1) | AU2015230094B2 (ja) |
BR (1) | BR112016020783A2 (ja) |
CA (1) | CA2942289C (ja) |
DK (1) | DK3117005T3 (ja) |
EA (1) | EA201691809A1 (ja) |
FI (1) | FI3117005T3 (ja) |
IL (1) | IL247729B2 (ja) |
MX (1) | MX2016011585A (ja) |
PT (1) | PT3117005T (ja) |
UA (1) | UA120923C2 (ja) |
WO (1) | WO2015137802A1 (ja) |
ZA (1) | ZA201606552B (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111344412A (zh) * | 2017-07-10 | 2020-06-26 | 优尼科Ip有限公司 | 人类中aav基因疗法的手段和方法 |
JP2020532286A (ja) * | 2017-07-20 | 2020-11-12 | ユニキュアー アイピー ビー.ブイ. | 昆虫細胞における向上したaavカプシド産生 |
Families Citing this family (52)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2015191508A1 (en) | 2014-06-09 | 2015-12-17 | Voyager Therapeutics, Inc. | Chimeric capsids |
CN107106689A (zh) | 2014-11-05 | 2017-08-29 | 沃雅戈治疗公司 | 用于治疗帕金森病的aadc多核苷酸 |
SG11201703419UA (en) | 2014-11-14 | 2017-05-30 | Voyager Therapeutics Inc | Modulatory polynucleotides |
MX2017006216A (es) | 2014-11-14 | 2018-08-29 | Voyager Therapeutics Inc | Composiciones y métodos para tratar la esclerosis lateral amiotrófica (ela). |
EP3230441A4 (en) | 2014-12-12 | 2018-10-03 | Voyager Therapeutics, Inc. | Compositions and methods for the production of scaav |
MX2018012663A (es) | 2016-04-16 | 2019-07-08 | Univ Florida | Metodos para aumentar la capacidad de actividad biológica del virus adenoasociado recombinante producido mediante el sistema baculovirus. |
US11326182B2 (en) | 2016-04-29 | 2022-05-10 | Voyager Therapeutics, Inc. | Compositions for the treatment of disease |
US11299751B2 (en) | 2016-04-29 | 2022-04-12 | Voyager Therapeutics, Inc. | Compositions for the treatment of disease |
KR102392236B1 (ko) | 2016-05-18 | 2022-05-03 | 보이저 테라퓨틱스, 인크. | 조절성 폴리뉴클레오티드 |
SG11201809643UA (en) | 2016-05-18 | 2018-12-28 | Voyager Therapeutics Inc | Compositions and methods of treating huntington's disease |
SG11201901221YA (en) * | 2016-08-15 | 2019-03-28 | Genzyme Corp | Methods for detecting aav |
EP3510161A4 (en) | 2016-08-23 | 2020-04-22 | Akouos, Inc. | COMPOSITIONS AND METHODS FOR TREATING PERSONAL HEARING LOSS IN A PERSON |
EP3831281A1 (en) | 2016-08-30 | 2021-06-09 | The Regents of The University of California | Methods for biomedical targeting and delivery and devices and systems for practicing the same |
EP3619308A4 (en) | 2017-05-05 | 2021-01-27 | Voyager Therapeutics, Inc. | COMPOSITIONS AND METHODS OF TREATMENT FOR HUNTINGTON'S MORBUS |
CA3061652A1 (en) | 2017-05-05 | 2018-11-08 | Voyager Therapeutics, Inc. | Compositions and methods of treating amyotrophic lateral sclerosis (als) |
JOP20190269A1 (ar) | 2017-06-15 | 2019-11-20 | Voyager Therapeutics Inc | بولي نوكليوتيدات aadc لعلاج مرض باركنسون |
JP7229989B2 (ja) | 2017-07-17 | 2023-02-28 | ボイジャー セラピューティクス インコーポレイテッド | 軌道アレイガイドシステム |
KR20200044793A (ko) | 2017-08-03 | 2020-04-29 | 보이저 테라퓨틱스, 인크. | Aav의 전달을 위한 조성물 및 방법 |
WO2019079242A1 (en) | 2017-10-16 | 2019-04-25 | Voyager Therapeutics, Inc. | TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS (ALS) |
JP7502991B2 (ja) | 2017-10-16 | 2024-06-19 | ボイジャー セラピューティクス インコーポレイテッド | 筋萎縮性側索硬化症(als)の治療 |
CN111527201A (zh) * | 2017-12-29 | 2020-08-11 | 优尼科Ip有限公司 | 修饰的病毒载体及其制备和使用方法 |
GB201800903D0 (en) | 2018-01-19 | 2018-03-07 | Oxford Genetics Ltd | Vectors |
WO2019241486A1 (en) | 2018-06-13 | 2019-12-19 | Voyager Therapeutics, Inc. | Engineered 5' untranslated regions (5' utr) for aav production |
US11702673B2 (en) * | 2018-10-18 | 2023-07-18 | University Of Florida Research Foundation, Incorporated | Methods of enhancing biological potency of baculovirus system-produced recombinant adeno-associated virus |
WO2020104480A1 (en) | 2018-11-19 | 2020-05-28 | Uniqure Biopharma B.V. | Adeno-associated virus vectors for expressing fviii mimetics and uses thereof |
CA3119721A1 (en) | 2018-11-19 | 2020-05-28 | Uniqure Ip B.V. | A companion diagnostic to monitor the effects of gene therapy |
EP3883582A1 (en) | 2018-11-19 | 2021-09-29 | uniQure IP B.V. | Method and means to deliver mirna to target cells |
SG11202107645RA (en) | 2019-01-18 | 2021-08-30 | Voyager Therapeutics Inc | Methods and systems for producing aav particles |
WO2020168222A1 (en) * | 2019-02-15 | 2020-08-20 | Generation Bio Co. | Modulation of rep protein activity in closed-ended dna (cedna) production |
CN111084888B (zh) * | 2019-03-15 | 2021-12-28 | 北京锦篮基因科技有限公司 | 一种用于治疗严重高甘油三酯血症的基因药物 |
MX2021013267A (es) * | 2019-04-29 | 2021-11-17 | Univ Pennsylvania | Nuevas capsides de aav y composiciones que las contienen. |
PE20212357A1 (es) * | 2019-05-24 | 2021-12-17 | Regeneron Pharma | Particulas virales modificadas y usos de estas |
US20220251600A1 (en) * | 2019-06-27 | 2022-08-11 | X-Chem, Inc. | Recombinant transfer vectors for protein expression in insect and mammalian cells |
US10557149B1 (en) * | 2019-07-15 | 2020-02-11 | Vigene Biosciences, Inc. | Recombinantly-modified adeno-associated virus helper vectors and their use to improve the packaging efficiency of recombinantly-modified adeno-associated virus |
WO2021053018A1 (en) | 2019-09-16 | 2021-03-25 | Uniqure Ip B.V. | Targeting misspliced transcripts in genetic disorders |
BR112022016596A2 (pt) | 2020-02-21 | 2022-11-16 | Akouos Inc | Composições e métodos para o tratamento de debilitação auditiva não associada à idade em um indivíduo humano |
WO2021195491A2 (en) * | 2020-03-26 | 2021-09-30 | Asklepios Biopharmaceutical, Inc. | Inducible promoter for viral vector production |
CA3169087A1 (en) | 2020-04-02 | 2021-10-07 | David Johannes Francois DU PLESSIS | Dual bifunctional vectors for aav production |
CN115867647A (zh) | 2020-04-02 | 2023-03-28 | 优尼科生物制药有限公司 | 新型细胞系 |
WO2022188797A1 (en) | 2021-03-09 | 2022-09-15 | Huigene Therapeutics Co., Ltd. | Engineered crispr/cas13 system and uses thereof |
WO2022207899A1 (en) | 2021-04-02 | 2022-10-06 | Uniqure Biopharma B.V. | Methods for producing single insect cell clones |
CA3219847A1 (en) | 2021-06-02 | 2022-12-08 | Sander Jan Hendrik Van Deventer | Adeno-associated virus vectors modified to bind high-density lipoprotein |
AU2022286647A1 (en) | 2021-06-02 | 2023-11-30 | Uniqure Biopharma B.V. | Insect cell production of parvoviral vectors with modified capsid proteins |
US20240287545A1 (en) | 2021-06-21 | 2024-08-29 | Uniqure Biopharma B.V. | Improved lysis procedures |
WO2023283962A1 (en) | 2021-07-16 | 2023-01-19 | Huigene Therapeutics Co., Ltd. | Modified aav capsid for gene therapy and methods thereof |
EP4392434A1 (en) | 2021-08-26 | 2024-07-03 | uniQure biopharma B.V. | Insect cell-produced high potency aav vectors with cns-tropism |
CN114703203B (zh) * | 2022-02-11 | 2024-08-06 | 上海渤因生物科技有限公司 | 杆状病毒载体及其用途 |
WO2023198745A1 (en) | 2022-04-12 | 2023-10-19 | Uniqure Biopharma B.V. | Nucleic acid regulation of apoe |
WO2023198702A1 (en) | 2022-04-12 | 2023-10-19 | Uniqure Biopharma B.V. | Nucleic acid regulation of c9orf72 |
WO2023198662A1 (en) | 2022-04-12 | 2023-10-19 | Uniqure Biopharma B.V. | Novel systems for nucleic acid regulation |
WO2023198663A1 (en) | 2022-04-12 | 2023-10-19 | Uniqure Biopharma B.V. | Nucleic acid regulation of snca |
WO2024078584A1 (zh) * | 2022-10-13 | 2024-04-18 | 康霖生物科技(杭州)有限公司 | 腺相关病毒的衣壳蛋白编码基因改造方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003042361A2 (en) * | 2001-11-09 | 2003-05-22 | Government Of The United States Of America, Department Of Health And Human Services | Production of adeno-associated virus in insect cells |
JP2009512436A (ja) * | 2005-10-20 | 2009-03-26 | アムステルダム モレキュラー セラピューティクス ビー.ブイ. | 昆虫細胞で産生される改良されたaavベクター |
JP2009540823A (ja) * | 2006-06-21 | 2009-11-26 | アムステルダム モレキュラー セラピューティクス ビー.ブイ. | 昆虫細胞におけるaavの生成に有用なaav−rep78の翻訳の改変型開始コドンを有するベクター |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4745051A (en) | 1983-05-27 | 1988-05-17 | The Texas A&M University System | Method for producing a recombinant baculovirus expression vector |
DE60039880D1 (en) | 1999-06-24 | 2008-09-25 | Amsterdam Molecular Therapeutics Bv | Therapie mit lipoproteinlipase (lpl) variant |
US6723551B2 (en) | 2001-11-09 | 2004-04-20 | The United States Of America As Represented By The Department Of Health And Human Services | Production of adeno-associated virus in insect cells |
AU2002359284A1 (en) | 2001-12-17 | 2003-06-30 | The Trustees Of The University Of Pennsylvania | Adeno-associated virus (aav) serotype 9 sequences, vectors containing same, and uses therefor |
WO2003074714A1 (en) | 2002-03-05 | 2003-09-12 | Stichting Voor De Technische Wetenschappen | Baculovirus expression system |
DK2292780T3 (en) | 2003-09-30 | 2017-12-04 | Univ Pennsylvania | Clades and sequences of adeno-associated virus (AAV), vectors containing them, and uses thereof |
WO2006036502A2 (en) | 2004-09-22 | 2006-04-06 | St. Jude Children's Research Hospital | Improved expression of factor ix in gene therapy vectors |
JP5634262B2 (ja) | 2007-07-26 | 2014-12-03 | ユニキュアー アイピー ビー.ブイ. | 差次的コドンバイアスを有する反復コード配列を含むバキュロウイルスベクター |
WO2009154452A1 (en) | 2008-06-17 | 2009-12-23 | Amsterdam Molecular Therapeutics B.V. | Parvoviral capsid with incorporated Gly-Ala repeat region |
WO2011122950A1 (en) | 2010-04-01 | 2011-10-06 | Amsterdam Molecular Therapeutics (Amt) Ip B.V. | Monomeric duplex aav vectors |
-
2015
- 2015-03-10 IL IL247729A patent/IL247729B2/en unknown
- 2015-03-10 AU AU2015230094A patent/AU2015230094B2/en active Active
- 2015-03-10 PT PT157154766T patent/PT3117005T/pt unknown
- 2015-03-10 BR BR112016020783A patent/BR112016020783A2/pt not_active Application Discontinuation
- 2015-03-10 FI FIEP15715476.6T patent/FI3117005T3/fi active
- 2015-03-10 MX MX2016011585A patent/MX2016011585A/es unknown
- 2015-03-10 CA CA2942289A patent/CA2942289C/en active Active
- 2015-03-10 US US15/124,139 patent/US10837027B2/en active Active
- 2015-03-10 KR KR1020167026098A patent/KR102572449B1/ko active IP Right Grant
- 2015-03-10 EA EA201691809A patent/EA201691809A1/ru unknown
- 2015-03-10 DK DK15715476.6T patent/DK3117005T3/da active
- 2015-03-10 WO PCT/NL2015/050149 patent/WO2015137802A1/en active Application Filing
- 2015-03-10 JP JP2016555770A patent/JP6683397B2/ja active Active
- 2015-03-10 EP EP15715476.6A patent/EP3117005B1/en active Active
- 2015-03-10 CN CN201580019215.0A patent/CN106459984B/zh active Active
- 2015-03-10 UA UAA201609350A patent/UA120923C2/uk unknown
-
2016
- 2016-09-22 ZA ZA2016/06552A patent/ZA201606552B/en unknown
-
2020
- 2020-01-06 JP JP2020000121A patent/JP2020062045A/ja active Pending
- 2020-11-05 US US17/090,807 patent/US20210222198A1/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003042361A2 (en) * | 2001-11-09 | 2003-05-22 | Government Of The United States Of America, Department Of Health And Human Services | Production of adeno-associated virus in insect cells |
JP2009512436A (ja) * | 2005-10-20 | 2009-03-26 | アムステルダム モレキュラー セラピューティクス ビー.ブイ. | 昆虫細胞で産生される改良されたaavベクター |
JP2009540823A (ja) * | 2006-06-21 | 2009-11-26 | アムステルダム モレキュラー セラピューティクス ビー.ブイ. | 昆虫細胞におけるaavの生成に有用なaav−rep78の翻訳の改変型開始コドンを有するベクター |
Non-Patent Citations (1)
Title |
---|
JOURNAL OF VIROLOGY, vol. 80, no. 4, JPN6019000795, 2006, pages 1874 - 1885, ISSN: 0003958775 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111344412A (zh) * | 2017-07-10 | 2020-06-26 | 优尼科Ip有限公司 | 人类中aav基因疗法的手段和方法 |
JP2020526203A (ja) * | 2017-07-10 | 2020-08-31 | ユニキュアー アイピー ビー.ブイ. | ヒトにおけるaav遺伝子療法のための手段及び方法 |
JP2020532286A (ja) * | 2017-07-20 | 2020-11-12 | ユニキュアー アイピー ビー.ブイ. | 昆虫細胞における向上したaavカプシド産生 |
Also Published As
Publication number | Publication date |
---|---|
JP2020062045A (ja) | 2020-04-23 |
EA201691809A1 (ru) | 2017-01-30 |
AU2015230094A1 (en) | 2016-09-15 |
CN106459984B (zh) | 2021-09-07 |
CA2942289A1 (en) | 2015-09-17 |
AU2015230094A9 (en) | 2016-09-22 |
CA2942289C (en) | 2024-05-21 |
US20170356008A1 (en) | 2017-12-14 |
EP3117005A1 (en) | 2017-01-18 |
US20210222198A1 (en) | 2021-07-22 |
CN106459984A (zh) | 2017-02-22 |
BR112016020783A2 (pt) | 2017-10-03 |
PT3117005T (pt) | 2024-07-30 |
JP6683397B2 (ja) | 2020-04-22 |
FI3117005T3 (fi) | 2024-08-29 |
DK3117005T3 (da) | 2024-08-12 |
ZA201606552B (en) | 2017-11-29 |
IL247729A0 (en) | 2016-11-30 |
KR20160131032A (ko) | 2016-11-15 |
WO2015137802A1 (en) | 2015-09-17 |
US10837027B2 (en) | 2020-11-17 |
EP3117005B1 (en) | 2024-07-03 |
IL247729B1 (en) | 2023-05-01 |
KR102572449B1 (ko) | 2023-08-31 |
MX2016011585A (es) | 2016-11-29 |
UA120923C2 (uk) | 2020-03-10 |
AU2015230094B2 (en) | 2021-05-27 |
IL247729B2 (en) | 2023-09-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20210222198A1 (en) | Further improved aav vectors produced in insect cells | |
US11667931B2 (en) | AAV capsid production in insect cells | |
JP5305913B2 (ja) | 昆虫細胞で産生される改良されたaavベクター | |
EP2035564B1 (en) | Vectors with modified initiation codon for the translation of aav-rep78 useful for production of aav in insect cells | |
AU2022286647A1 (en) | Insect cell production of parvoviral vectors with modified capsid proteins | |
EA042960B1 (ru) | Молекула нуклеиновой кислоты, конструкция нуклеиновой кислоты, клетка насекомого и способ получения aav в клетке насекомого |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180219 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20181226 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190122 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190422 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190624 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20190903 |
|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20190920 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200106 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20200107 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20200127 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200225 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200323 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6683397 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |