JP2023535232A - 眼疾患の処置のための組成物および方法 - Google Patents
眼疾患の処置のための組成物および方法 Download PDFInfo
- Publication number
- JP2023535232A JP2023535232A JP2023512465A JP2023512465A JP2023535232A JP 2023535232 A JP2023535232 A JP 2023535232A JP 2023512465 A JP2023512465 A JP 2023512465A JP 2023512465 A JP2023512465 A JP 2023512465A JP 2023535232 A JP2023535232 A JP 2023535232A
- Authority
- JP
- Japan
- Prior art keywords
- sequence
- seq
- rpe65
- promoter
- aav
- 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.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims abstract description 63
- 239000000203 mixture Substances 0.000 title claims description 50
- 238000011282 treatment Methods 0.000 title abstract description 11
- 208000030533 eye disease Diseases 0.000 title description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 44
- 201000003533 Leber congenital amaurosis Diseases 0.000 claims abstract description 34
- 108091026890 Coding region Proteins 0.000 claims description 231
- 239000002245 particle Substances 0.000 claims description 201
- 108090000623 proteins and genes Proteins 0.000 claims description 141
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 138
- 102000040430 polynucleotide Human genes 0.000 claims description 130
- 108091033319 polynucleotide Proteins 0.000 claims description 130
- 239000002157 polynucleotide Substances 0.000 claims description 130
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 129
- 229920001184 polypeptide Polymers 0.000 claims description 119
- 125000003729 nucleotide group Chemical group 0.000 claims description 103
- 102000004169 proteins and genes Human genes 0.000 claims description 101
- 239000002773 nucleotide Substances 0.000 claims description 100
- 108020004705 Codon Proteins 0.000 claims description 40
- 241000702421 Dependoparvovirus Species 0.000 claims description 33
- 241000701447 unidentified baculovirus Species 0.000 claims description 26
- 230000001225 therapeutic effect Effects 0.000 claims description 24
- 108020004414 DNA Proteins 0.000 claims description 23
- 239000013598 vector Substances 0.000 claims description 21
- 108091034057 RNA (poly(A)) Proteins 0.000 claims description 20
- 102100038247 Retinol-binding protein 3 Human genes 0.000 claims description 20
- 239000007924 injection Substances 0.000 claims description 19
- 238000002347 injection Methods 0.000 claims description 19
- 241000238631 Hexapoda Species 0.000 claims description 17
- 230000035772 mutation Effects 0.000 claims description 17
- 101100118093 Drosophila melanogaster eEF1alpha2 gene Proteins 0.000 claims description 16
- 108010048996 interstitial retinol-binding protein Proteins 0.000 claims description 14
- 241000282414 Homo sapiens Species 0.000 claims description 13
- 208000032578 Inherited retinal disease Diseases 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 102000029752 retinol binding Human genes 0.000 claims description 12
- 108091000053 retinol binding Proteins 0.000 claims description 12
- 102100031176 Retinoid isomerohydrolase Human genes 0.000 claims description 11
- 239000012634 fragment Substances 0.000 claims description 11
- 108090000565 Capsid Proteins Proteins 0.000 claims description 10
- 102100023321 Ceruloplasmin Human genes 0.000 claims description 10
- 101001078886 Homo sapiens Retinaldehyde-binding protein 1 Proteins 0.000 claims description 10
- 241001465754 Metazoa Species 0.000 claims description 10
- 101150116978 RPE65 gene Proteins 0.000 claims description 10
- 102100028001 Retinaldehyde-binding protein 1 Human genes 0.000 claims description 10
- 101000801643 Homo sapiens Retinal-specific phospholipid-transporting ATPase ABCA4 Proteins 0.000 claims description 8
- 102100033356 Lecithin retinol acyltransferase Human genes 0.000 claims description 8
- 102100033617 Retinal-specific phospholipid-transporting ATPase ABCA4 Human genes 0.000 claims description 8
- 102100038054 Retinol dehydrogenase 12 Human genes 0.000 claims description 8
- 102100024844 Retinol dehydrogenase 8 Human genes 0.000 claims description 8
- 108010084957 lecithin-retinol acyltransferase Proteins 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 108010035291 retinol dehydrogenase Proteins 0.000 claims description 8
- NCYCYZXNIZJOKI-IOUUIBBYSA-N 11-cis-retinal Chemical compound O=C/C=C(\C)/C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-IOUUIBBYSA-N 0.000 claims description 7
- 241001529936 Murinae Species 0.000 claims description 7
- 108091093126 WHP Posttrascriptional Response Element Proteins 0.000 claims description 7
- 108091008695 photoreceptors Proteins 0.000 claims description 7
- 101150021183 65 gene Proteins 0.000 claims description 6
- 102000029816 Collagenase Human genes 0.000 claims description 6
- 108060005980 Collagenase Proteins 0.000 claims description 6
- 108091004242 G-Protein-Coupled Receptor Kinase 1 Proteins 0.000 claims description 6
- 102000004437 G-Protein-Coupled Receptor Kinase 1 Human genes 0.000 claims description 6
- 101000742938 Homo sapiens Retinol dehydrogenase 12 Proteins 0.000 claims description 6
- 101000687592 Homo sapiens Retinol dehydrogenase 8 Proteins 0.000 claims description 6
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 claims description 6
- 101710097927 Retinal-binding protein Proteins 0.000 claims description 6
- 102100038053 Retinol dehydrogenase 5 Human genes 0.000 claims description 6
- 102000004330 Rhodopsin Human genes 0.000 claims description 6
- 108090000820 Rhodopsin Proteins 0.000 claims description 6
- 108090000799 Rhodopsin kinases Proteins 0.000 claims description 6
- 101150079992 Timp3 gene Proteins 0.000 claims description 6
- 102000005406 Tissue Inhibitor of Metalloproteinase-3 Human genes 0.000 claims description 6
- 229960002424 collagenase Drugs 0.000 claims description 6
- 230000002829 reductive effect Effects 0.000 claims description 6
- 102000024458 retinal binding proteins Human genes 0.000 claims description 6
- 108010042033 retinol dehydrogenase 5 Proteins 0.000 claims description 6
- 201000004569 Blindness Diseases 0.000 claims description 4
- 101000792933 Homo sapiens AT-rich interactive domain-containing protein 4A Proteins 0.000 claims description 4
- 101000756373 Homo sapiens Retinol-binding protein 1 Proteins 0.000 claims description 4
- 101000665873 Homo sapiens Retinol-binding protein 3 Proteins 0.000 claims description 4
- 101000904152 Homo sapiens Transcription factor E2F1 Proteins 0.000 claims description 4
- 102100022941 Retinol-binding protein 1 Human genes 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 206010010356 Congenital anomaly Diseases 0.000 claims description 2
- 108010000521 Human Growth Hormone Proteins 0.000 claims description 2
- 102000002265 Human Growth Hormone Human genes 0.000 claims description 2
- 239000000854 Human Growth Hormone Substances 0.000 claims description 2
- 206010001902 amaurosis Diseases 0.000 claims description 2
- 108010006025 bovine growth hormone Proteins 0.000 claims description 2
- 101000729271 Homo sapiens Retinoid isomerohydrolase Proteins 0.000 claims 8
- 101001111656 Homo sapiens Retinol dehydrogenase 10 Proteins 0.000 claims 2
- 101001111655 Homo sapiens Retinol dehydrogenase 11 Proteins 0.000 claims 2
- 208000035719 Maculopathy Diseases 0.000 claims 2
- 102100023918 Retinol dehydrogenase 10 Human genes 0.000 claims 2
- 102100023916 Retinol dehydrogenase 11 Human genes 0.000 claims 2
- 230000005764 inhibitory process Effects 0.000 claims 2
- 208000002780 macular degeneration Diseases 0.000 claims 2
- 241000206607 Porphyra umbilicalis Species 0.000 claims 1
- 239000002356 single layer Substances 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 200
- 230000014509 gene expression Effects 0.000 description 143
- 239000000090 biomarker Substances 0.000 description 114
- 208000002267 Anti-neutrophil cytoplasmic antibody-associated vasculitis Diseases 0.000 description 95
- 235000018102 proteins Nutrition 0.000 description 85
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 38
- 241001164825 Adeno-associated virus - 8 Species 0.000 description 36
- 235000001014 amino acid Nutrition 0.000 description 35
- 230000003612 virological effect Effects 0.000 description 35
- 241000649045 Adeno-associated virus 10 Species 0.000 description 32
- 241000649046 Adeno-associated virus 11 Species 0.000 description 32
- 241000649047 Adeno-associated virus 12 Species 0.000 description 32
- 241000300529 Adeno-associated virus 13 Species 0.000 description 32
- 241000425548 Adeno-associated virus 3A Species 0.000 description 32
- 241000649044 Adeno-associated virus 9 Species 0.000 description 32
- 239000003623 enhancer Substances 0.000 description 30
- 150000001413 amino acids Chemical class 0.000 description 26
- 125000003275 alpha amino acid group Chemical group 0.000 description 22
- 210000001519 tissue Anatomy 0.000 description 20
- 238000006467 substitution reaction Methods 0.000 description 18
- 241000700605 Viruses Species 0.000 description 17
- 241000701022 Cytomegalovirus Species 0.000 description 16
- 238000007792 addition Methods 0.000 description 16
- 101710197658 Capsid protein VP1 Proteins 0.000 description 15
- 230000037430 deletion Effects 0.000 description 15
- 238000012217 deletion Methods 0.000 description 15
- 101710132601 Capsid protein Proteins 0.000 description 14
- 101710081079 Minor spike protein H Proteins 0.000 description 14
- 101710118046 RNA-directed RNA polymerase Proteins 0.000 description 14
- 101710108545 Viral protein 1 Proteins 0.000 description 14
- 201000010099 disease Diseases 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 230000008488 polyadenylation Effects 0.000 description 14
- 210000002845 virion Anatomy 0.000 description 14
- 108010054126 retinoid isomerohydrolase Proteins 0.000 description 13
- 150000007523 nucleic acids Chemical group 0.000 description 12
- 238000005457 optimization Methods 0.000 description 12
- 238000004806 packaging method and process Methods 0.000 description 12
- 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 9
- 108091028043 Nucleic acid sequence Proteins 0.000 description 9
- 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 9
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 9
- 238000011144 upstream manufacturing Methods 0.000 description 9
- 241000699670 Mus sp. Species 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 235000020945 retinal Nutrition 0.000 description 8
- 239000011604 retinal Substances 0.000 description 8
- 230000002207 retinal effect Effects 0.000 description 8
- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 8
- 241000282412 Homo Species 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 7
- 102000012464 Retinol dehydrogenase 10 Human genes 0.000 description 6
- 108050002017 Retinol dehydrogenase 10 Proteins 0.000 description 6
- 102000039446 nucleic acids Human genes 0.000 description 6
- 108020004707 nucleic acids Proteins 0.000 description 6
- 239000013608 rAAV vector Substances 0.000 description 6
- 230000010076 replication Effects 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 101000805768 Banna virus (strain Indonesia/JKT-6423/1980) mRNA (guanine-N(7))-methyltransferase Proteins 0.000 description 5
- 101000686790 Chaetoceros protobacilladnavirus 2 Replication-associated protein Proteins 0.000 description 5
- 101000864475 Chlamydia phage 1 Internal scaffolding protein VP3 Proteins 0.000 description 5
- 101000803553 Eumenes pomiformis Venom peptide 3 Proteins 0.000 description 5
- 101000583961 Halorubrum pleomorphic virus 1 Matrix protein Proteins 0.000 description 5
- 241000700584 Simplexvirus Species 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 125000000539 amino acid group Chemical group 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 210000004962 mammalian cell Anatomy 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 239000013607 AAV vector Substances 0.000 description 4
- 102100022794 Bestrophin-1 Human genes 0.000 description 4
- 241000214054 Equine rhinitis A virus Species 0.000 description 4
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 4
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 4
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 4
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 4
- 101000903449 Homo sapiens Bestrophin-1 Proteins 0.000 description 4
- 102400001132 Melanin-concentrating hormone Human genes 0.000 description 4
- 101800002739 Melanin-concentrating hormone Proteins 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 241000277269 Oncorhynchus masou Species 0.000 description 4
- 108700026244 Open Reading Frames Proteins 0.000 description 4
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 4
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 4
- 241000714474 Rous sarcoma virus Species 0.000 description 4
- 241001648840 Thosea asigna virus Species 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- ORRDHOMWDPJSNL-UHFFFAOYSA-N melanin concentrating hormone Chemical compound N1C(=O)C(C(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CCSC)NC(=O)C(NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(NC(=O)C(N)CC(O)=O)C(C)O)CCSC)CSSCC(C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)NC(CCC(O)=O)C(=O)NC(C(C)C)C(O)=O)NC(=O)C2CCCN2C(=O)C(CCCNC(N)=N)NC(=O)C1CC1=CC=C(O)C=C1 ORRDHOMWDPJSNL-UHFFFAOYSA-N 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 229940124624 oral corticosteroid Drugs 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 230000004393 visual impairment Effects 0.000 description 4
- 208000020938 vitelliform macular dystrophy 2 Diseases 0.000 description 4
- 241000202702 Adeno-associated virus - 3 Species 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 206010047571 Visual impairment Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 210000000234 capsid Anatomy 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 229920001983 poloxamer Polymers 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000017854 proteolysis Effects 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 241001515965 unidentified phage Species 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 11-cis-Retinol Chemical compound OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 2
- FPIPGXGPPPQFEQ-HPNHMNAASA-N 11-cis-retinol Natural products OCC=C(C)C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-HPNHMNAASA-N 0.000 description 2
- 102100038794 17-beta-hydroxysteroid dehydrogenase type 6 Human genes 0.000 description 2
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 2
- 241000710189 Aphthovirus Species 0.000 description 2
- 241000710190 Cardiovirus Species 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical group O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 2
- 108010020056 Hydrogenase Proteins 0.000 description 2
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- 241000701460 JC polyomavirus Species 0.000 description 2
- 108010063312 Metalloproteins Proteins 0.000 description 2
- 102000010750 Metalloproteins Human genes 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 238000013324 OneBac system Methods 0.000 description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 208000037418 Rare genetic eye disease Diseases 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- NCYCYZXNIZJOKI-OVSJKPMPSA-N Retinaldehyde Chemical compound O=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-OVSJKPMPSA-N 0.000 description 2
- 101710178616 Retinol dehydrogenase 12 Proteins 0.000 description 2
- 101710189258 Retinol dehydrogenase 8 Proteins 0.000 description 2
- 101710137010 Retinol-binding protein 3 Proteins 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 108020004566 Transfer RNA Proteins 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 2
- 210000004507 artificial chromosome Anatomy 0.000 description 2
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
- 235000013871 bee wax Nutrition 0.000 description 2
- 239000012166 beeswax Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 201000000053 blastoma Diseases 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000002571 electroretinography Methods 0.000 description 2
- 201000008184 embryoma Diseases 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 238000004191 hydrophobic interaction chromatography Methods 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 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 2
- 230000010354 integration Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 239000000816 peptidomimetic Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 229960000502 poloxamer Drugs 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 101150066583 rep gene Proteins 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 210000001525 retina Anatomy 0.000 description 2
- 230000004243 retinal function Effects 0.000 description 2
- 239000000790 retinal pigment Substances 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 238000013351 twoBac system Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 208000029257 vision disease Diseases 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- NCYCYZXNIZJOKI-HPNHMNAASA-N 11Z-retinal Natural products CC(=C/C=O)C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-HPNHMNAASA-N 0.000 description 1
- BFUUJUGQJUTPAF-UHFFFAOYSA-N 2-(3-amino-4-propoxybenzoyl)oxyethyl-diethylazanium;chloride Chemical compound [Cl-].CCCOC1=CC=C(C(=O)OCC[NH+](CC)CC)C=C1N BFUUJUGQJUTPAF-UHFFFAOYSA-N 0.000 description 1
- 101710122462 65 kDa protein Proteins 0.000 description 1
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 1
- 241000238421 Arthropoda Species 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 241001367049 Autographa Species 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 241000701412 Baculoviridae Species 0.000 description 1
- 206010005176 Blindness congenital Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 101150044789 Cap gene Proteins 0.000 description 1
- 101710197665 Capsid protein VP2 Proteins 0.000 description 1
- 101800001319 Capsid protein VP3 Proteins 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 108091029523 CpG island Proteins 0.000 description 1
- 108091029430 CpG site Proteins 0.000 description 1
- 241000450599 DNA viruses Species 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 102000010175 Opsin Human genes 0.000 description 1
- 108050001704 Opsin Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000004020 Oxygenases Human genes 0.000 description 1
- 108090000417 Oxygenases Proteins 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 241000701945 Parvoviridae Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 101710182846 Polyhedrin Proteins 0.000 description 1
- 101710150114 Protein rep Proteins 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 101710152114 Replication protein Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 201000007737 Retinal degeneration Diseases 0.000 description 1
- 206010038848 Retinal detachment Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- HOBWAPHTEJGALG-JKCMADFCSA-N [(1r,5s)-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate;sulfate Chemical compound [O-]S([O-])(=O)=O.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1 HOBWAPHTEJGALG-JKCMADFCSA-N 0.000 description 1
- 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 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000010516 arginylation Effects 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- 229960002028 atropine sulfate Drugs 0.000 description 1
- 208000025341 autosomal recessive disease Diseases 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 210000004899 c-terminal region Anatomy 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
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000004300 dark adaptation Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 230000004424 eye movement Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000004545 gene duplication Effects 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 125000004404 heteroalkyl group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 230000006122 isoprenylation Effects 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 208000018769 loss of vision Diseases 0.000 description 1
- 231100000864 loss of vision Toxicity 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 206010029864 nystagmus Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003733 phenylephrine hydrochloride Drugs 0.000 description 1
- OCYSGIYOVXAGKQ-FVGYRXGTSA-N phenylephrine hydrochloride Chemical compound [H+].[Cl-].CNC[C@H](O)C1=CC=CC(O)=C1 OCYSGIYOVXAGKQ-FVGYRXGTSA-N 0.000 description 1
- 210000000608 photoreceptor cell Anatomy 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 230000016732 phototransduction Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 229960001371 proparacaine hydrochloride Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 230000001179 pupillary effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004258 retinal degeneration Effects 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 230000004283 retinal dysfunction Effects 0.000 description 1
- 210000000880 retinal rod photoreceptor cell Anatomy 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 108020004418 ribosomal RNA Proteins 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 230000019635 sulfation Effects 0.000 description 1
- 238000005670 sulfation reaction Methods 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000026676 system process Effects 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 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
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 241000701366 unidentified nuclear polyhedrosis viruses Species 0.000 description 1
- 230000007442 viral DNA synthesis Effects 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
- A61K48/0058—Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/52—Isomerases (5)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- C12N9/18—Carboxylic ester hydrolases (3.1.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/01—Carboxylic ester hydrolases (3.1.1)
- C12Y301/01064—Retinoid isomerohydrolase (3.1.1.64)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
-
- 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
- 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
- C12N2750/14171—Demonstrated in vivo effect
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Ophthalmology & Optometry (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Virology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010704946.1 | 2020-07-21 | ||
| CN202010704946.1A CN113952471A (zh) | 2020-07-21 | 2020-07-21 | 用于治疗眼部疾病的组合物和方法 |
| CN202110378979.6 | 2021-04-08 | ||
| CN202110378979 | 2021-04-08 | ||
| PCT/CN2021/107284 WO2022017363A1 (en) | 2020-07-21 | 2021-07-20 | Compositions and methods for the treatment of ocular diseases |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2023535232A true JP2023535232A (ja) | 2023-08-16 |
| JPWO2022017363A5 JPWO2022017363A5 (https=) | 2024-07-26 |
| JP2023535232A5 JP2023535232A5 (https=) | 2024-07-26 |
Family
ID=79728991
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2023512465A Withdrawn JP2023535232A (ja) | 2020-07-21 | 2021-07-20 | 眼疾患の処置のための組成物および方法 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20230321280A1 (https=) |
| EP (1) | EP4185335A1 (https=) |
| JP (1) | JP2023535232A (https=) |
| CN (1) | CN116368228A (https=) |
| AU (1) | AU2021314400A1 (https=) |
| CA (1) | CA3186818A1 (https=) |
| WO (1) | WO2022017363A1 (https=) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023187822A1 (en) * | 2022-03-28 | 2023-10-05 | Indian Institute Of Technology Kanpur | A system for an ocular gene therapy and a process for preparing thereof |
| WO2024077089A2 (en) * | 2022-10-04 | 2024-04-11 | Siren Biotechnology, Inc. | Modified cpg dinucleotides for recombinant viral vector production |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201502137D0 (en) * | 2015-02-09 | 2015-03-25 | Ucl Business Plc | Treatment |
| US20180161405A1 (en) * | 2015-06-04 | 2018-06-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Improved methods for treating ocular diseases by gene therapy |
| KR20200036912A (ko) * | 2017-07-31 | 2020-04-07 | 리플렉션 바이오테크놀러지스 리미티드 | 안과 질환을 위한 세포 모델 및 치료요법 |
| CN111118017B (zh) * | 2018-11-01 | 2023-10-03 | 上海朗昇生物科技有限公司 | 治疗Leber先天性黑蒙症的载体及其应用 |
-
2021
- 2021-07-20 WO PCT/CN2021/107284 patent/WO2022017363A1/en not_active Ceased
- 2021-07-20 AU AU2021314400A patent/AU2021314400A1/en not_active Abandoned
- 2021-07-20 JP JP2023512465A patent/JP2023535232A/ja not_active Withdrawn
- 2021-07-20 CN CN202180064406.4A patent/CN116368228A/zh active Pending
- 2021-07-20 CA CA3186818A patent/CA3186818A1/en active Pending
- 2021-07-20 EP EP21846029.3A patent/EP4185335A1/en not_active Withdrawn
-
2023
- 2023-01-20 US US18/157,577 patent/US20230321280A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN116368228A (zh) | 2023-06-30 |
| US20230321280A1 (en) | 2023-10-12 |
| WO2022017363A1 (en) | 2022-01-27 |
| AU2021314400A1 (en) | 2023-03-23 |
| CA3186818A1 (en) | 2022-01-27 |
| EP4185335A1 (en) | 2023-05-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3717636B1 (en) | Adeno-associated virus variant capsids and use for inhibiting angiogenesis | |
| CN113383010B (zh) | 具有经工程化改造的启动子的共济蛋白表达构建体及其使用方法 | |
| US20170007720A1 (en) | Methods and compositions for gene delivery to on bipolar cells | |
| US12467066B2 (en) | Compositions and methods for treating retinal disorders | |
| AU2021337530B2 (en) | Codon Optimized RPGRorf 15 Genes And Uses Thereof | |
| AU2024276934A1 (en) | Adeno-associated virus capsid protein, adeno-associated virus containing same, vector and use thereof | |
| US20230321280A1 (en) | Compositions and methods for the treatment of ocular diseases | |
| CN112029773B (zh) | 编码bdnf的核酸及其应用 | |
| WO2017120294A1 (en) | Methods and compositions for treatment of ocular disorders and blinding diseases | |
| CN108103096A (zh) | 一种先天性黒曚症的基因治疗药物 | |
| WO2020000641A1 (zh) | 编码人nadh脱氢酶亚单位蛋白的核酸及其应用 | |
| JPWO2022017363A5 (https=) | ||
| US20240307559A1 (en) | Kcnv2 gene therapy | |
| HK40092769A (zh) | 用於治疗眼部疾病的组合物和方法 | |
| CN112063625A (zh) | 编码arl2bp的核酸及其应用 | |
| JP2024521537A (ja) | 血友病ｂを処置するための組成物および方法 | |
| EP4658323A1 (en) | Recombinant adeno-associated virus vector | |
| Zheng et al. | Transduction of mouse retina by insect cell packaged recombinant adeno-associated viruses and their mutants via intravitreal injection | |
| AU2024342045A1 (en) | Aav variant capable of infecting inner ear | |
| KR20250156211A (ko) | 글루코실세라미다제 베타 1 결핍증과 관련된 신경 장애의 치료를 위한 조성물 및 방법 | |
| HK40030486A (en) | Compositions and methods for treating retinal disorders | |
| HK40030486B (en) | Compositions and methods for treating retinal disorders | |
| Belhoul-Fakir | Construction and optimization of novel recombinant Adeno-Associated Virus rAAV2/5 for targeting microglia to regulate immune responses during neuroinflammation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20230913 |
|
| A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20231030 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20231030 Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231030 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240717 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20240717 |
|
| A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20240729 |