CN105120901A - Rpgr x染色体连锁视网膜退化的aav介导的基因治疗 - Google Patents
Rpgr x染色体连锁视网膜退化的aav介导的基因治疗 Download PDFInfo
- Publication number
- CN105120901A CN105120901A CN201380045636.1A CN201380045636A CN105120901A CN 105120901 A CN105120901 A CN 105120901A CN 201380045636 A CN201380045636 A CN 201380045636A CN 105120901 A CN105120901 A CN 105120901A
- Authority
- CN
- China
- Prior art keywords
- fragment
- gene
- nucleotide sequence
- aav
- rpgr
- 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.)
- Pending
Links
- 101001104102 Homo sapiens X-linked retinitis pigmentosa GTPase regulator Proteins 0.000 title abstract description 81
- 102100040092 X-linked retinitis pigmentosa GTPase regulator Human genes 0.000 title abstract description 78
- 238000001415 gene therapy Methods 0.000 title description 13
- 201000007737 Retinal degeneration Diseases 0.000 title description 9
- 230000004258 retinal degeneration Effects 0.000 title description 7
- 230000001404 mediated effect Effects 0.000 title description 4
- 238000000034 method Methods 0.000 claims abstract description 137
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 89
- 239000000203 mixture Substances 0.000 claims abstract description 86
- 239000012634 fragment Substances 0.000 claims abstract description 80
- 150000007523 nucleic acids Chemical group 0.000 claims abstract description 51
- 108091028043 Nucleic acid sequence Proteins 0.000 claims abstract description 48
- 101150059532 RPGR gene Proteins 0.000 claims abstract description 46
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims abstract description 42
- 230000001105 regulatory effect Effects 0.000 claims abstract description 31
- 210000000608 photoreceptor cell Anatomy 0.000 claims abstract description 28
- 241000702421 Dependoparvovirus Species 0.000 claims abstract description 26
- 210000004027 cell Anatomy 0.000 claims description 80
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 78
- 201000010099 disease Diseases 0.000 claims description 75
- 230000002207 retinal effect Effects 0.000 claims description 55
- 238000011282 treatment Methods 0.000 claims description 53
- 239000013598 vector Substances 0.000 claims description 41
- 239000002773 nucleotide Substances 0.000 claims description 33
- 125000003729 nucleotide group Chemical group 0.000 claims description 33
- 238000002347 injection Methods 0.000 claims description 32
- 239000007924 injection Substances 0.000 claims description 32
- 241000702423 Adeno-associated virus - 2 Species 0.000 claims description 30
- 239000003937 drug carrier Substances 0.000 claims description 28
- 230000002265 prevention Effects 0.000 claims description 20
- 101000847476 Autographa californica nuclear polyhedrosis virus Uncharacterized 54.7 kDa protein in IAP1-SOD intergenic region Proteins 0.000 claims description 18
- 101000736075 Bacillus subtilis (strain 168) Uncharacterized protein YcbP Proteins 0.000 claims description 18
- 101001066788 Haemophilus phage HP1 (strain HP1c1) Probable portal protein Proteins 0.000 claims description 18
- 101000748192 Herpetosiphon aurantiacus Uncharacterized 15.4 kDa protein in HgiDIIM 5'region Proteins 0.000 claims description 18
- 238000003384 imaging method Methods 0.000 claims description 17
- 230000005856 abnormality Effects 0.000 claims description 16
- 101000829506 Homo sapiens Rhodopsin kinase GRK1 Proteins 0.000 claims description 14
- 230000006378 damage Effects 0.000 claims description 13
- 230000006872 improvement Effects 0.000 claims description 11
- 238000002560 therapeutic procedure Methods 0.000 claims description 11
- 108050001704 Opsin Proteins 0.000 claims description 10
- 102100038247 Retinol-binding protein 3 Human genes 0.000 claims description 10
- 241000700605 Viruses Species 0.000 claims description 9
- 230000000007 visual effect Effects 0.000 claims description 9
- 108010003730 Cone Opsins Proteins 0.000 claims description 8
- 102100023742 Rhodopsin kinase GRK1 Human genes 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 6
- 108020003175 receptors Proteins 0.000 claims description 6
- 102000008763 Neurofilament Proteins Human genes 0.000 claims description 5
- 108010088373 Neurofilament Proteins Proteins 0.000 claims description 5
- 210000005044 neurofilament Anatomy 0.000 claims description 5
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 claims description 4
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 claims description 4
- 108700024394 Exon Proteins 0.000 claims description 3
- 230000008859 change Effects 0.000 claims description 3
- 102000004190 Enzymes Human genes 0.000 claims description 2
- 108090000790 Enzymes Proteins 0.000 claims description 2
- 230000003376 axonal effect Effects 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims description 2
- 210000000225 synapse Anatomy 0.000 claims description 2
- 101710137010 Retinol-binding protein 3 Proteins 0.000 claims 3
- 238000012797 qualification Methods 0.000 claims 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- 208000027418 Wounds and injury Diseases 0.000 claims 1
- 238000003556 assay Methods 0.000 claims 1
- 208000014674 injury Diseases 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 201000004569 Blindness Diseases 0.000 abstract description 21
- 230000004393 visual impairment Effects 0.000 abstract description 15
- 108091008695 photoreceptors Proteins 0.000 description 87
- 230000035772 mutation Effects 0.000 description 50
- 241000282472 Canis lupus familiaris Species 0.000 description 42
- 230000014509 gene expression Effects 0.000 description 41
- 210000001525 retina Anatomy 0.000 description 41
- 230000006870 function Effects 0.000 description 40
- 230000004438 eyesight Effects 0.000 description 20
- 239000000047 product Substances 0.000 description 19
- 102000004169 proteins and genes Human genes 0.000 description 19
- 230000001225 therapeutic effect Effects 0.000 description 16
- 108700019146 Transgenes Proteins 0.000 description 14
- 238000002571 electroretinography Methods 0.000 description 14
- 230000007850 degeneration Effects 0.000 description 13
- 230000001939 inductive effect Effects 0.000 description 13
- 238000011833 dog model Methods 0.000 description 12
- 108010048996 interstitial retinol-binding protein Proteins 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 208000017442 Retinal disease Diseases 0.000 description 11
- 238000012014 optical coherence tomography Methods 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 10
- 210000000234 capsid Anatomy 0.000 description 10
- 210000001787 dendrite Anatomy 0.000 description 10
- 230000001965 increasing effect Effects 0.000 description 10
- 241000282465 Canis Species 0.000 description 9
- 102000010175 Opsin Human genes 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 9
- 241000282412 Homo Species 0.000 description 8
- 208000002352 blister Diseases 0.000 description 8
- 239000002299 complementary DNA Substances 0.000 description 8
- 230000003247 decreasing effect Effects 0.000 description 8
- 230000000750 progressive effect Effects 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 210000001766 X chromosome Anatomy 0.000 description 7
- 239000000969 carrier Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000003623 enhancer Substances 0.000 description 7
- 230000002068 genetic effect Effects 0.000 description 7
- 102000050172 human GRK1 Human genes 0.000 description 7
- 238000010172 mouse model Methods 0.000 description 7
- 230000002093 peripheral effect Effects 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- 108090000565 Capsid Proteins Proteins 0.000 description 6
- 102100023321 Ceruloplasmin Human genes 0.000 description 6
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- 230000007423 decrease Effects 0.000 description 6
- 210000001328 optic nerve Anatomy 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 230000004243 retinal function Effects 0.000 description 6
- 230000000946 synaptic effect Effects 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 230000008719 thickening Effects 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 239000013603 viral vector Substances 0.000 description 6
- 230000003612 virological effect Effects 0.000 description 6
- 230000004304 visual acuity Effects 0.000 description 6
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 5
- 208000006992 Color Vision Defects Diseases 0.000 description 5
- 241000701022 Cytomegalovirus Species 0.000 description 5
- 230000004544 DNA amplification Effects 0.000 description 5
- 101001043564 Homo sapiens Prolow-density lipoprotein receptor-related protein 1 Proteins 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 102100021923 Prolow-density lipoprotein receptor-related protein 1 Human genes 0.000 description 5
- 108010005063 Rod Opsins Proteins 0.000 description 5
- 201000000761 achromatopsia Diseases 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 201000007254 color blindness Diseases 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 230000001976 improved effect Effects 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 230000002018 overexpression Effects 0.000 description 5
- 210000000964 retinal cone photoreceptor cell Anatomy 0.000 description 5
- 238000012876 topography Methods 0.000 description 5
- 102100021411 C-terminal-binding protein 2 Human genes 0.000 description 4
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 4
- 101000729271 Homo sapiens Retinoid isomerohydrolase Proteins 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 108010029485 Protein Isoforms Proteins 0.000 description 4
- 102000001708 Protein Isoforms Human genes 0.000 description 4
- 102100031176 Retinoid isomerohydrolase Human genes 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- 230000001886 ciliary effect Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 230000004064 dysfunction Effects 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 238000002372 labelling Methods 0.000 description 4
- 210000000063 presynaptic terminal Anatomy 0.000 description 4
- 239000013646 rAAV2 vector Substances 0.000 description 4
- 238000007634 remodeling Methods 0.000 description 4
- 210000000880 retinal rod photoreceptor cell Anatomy 0.000 description 4
- 238000004904 shortening Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 239000013607 AAV vector Substances 0.000 description 3
- 208000002267 Anti-neutrophil cytoplasmic antibody-associated vasculitis Diseases 0.000 description 3
- 101710178053 C-terminal-binding protein 2 Proteins 0.000 description 3
- 206010010356 Congenital anomaly Diseases 0.000 description 3
- 108091035707 Consensus sequence Proteins 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 208000003098 Ganglion Cysts Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 208000022873 Ocular disease Diseases 0.000 description 3
- 208000034461 Progressive cone dystrophy Diseases 0.000 description 3
- 206010038923 Retinopathy Diseases 0.000 description 3
- 102000005801 Rod Opsins Human genes 0.000 description 3
- 241000714474 Rous sarcoma virus Species 0.000 description 3
- 208000005400 Synovial Cyst Diseases 0.000 description 3
- 125000003275 alpha amino acid group Chemical group 0.000 description 3
- 230000007844 axonal damage Effects 0.000 description 3
- 239000003855 balanced salt solution Substances 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 102000014823 calbindin Human genes 0.000 description 3
- 108060001061 calbindin Proteins 0.000 description 3
- 230000003915 cell function Effects 0.000 description 3
- 230000004456 color vision Effects 0.000 description 3
- 201000008615 cone dystrophy Diseases 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000002695 general anesthesia Methods 0.000 description 3
- 210000002287 horizontal cell Anatomy 0.000 description 3
- 102000050188 human RPGR Human genes 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000003607 modifier Substances 0.000 description 3
- 210000004126 nerve fiber Anatomy 0.000 description 3
- 230000014511 neuron projection development Effects 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 230000002688 persistence Effects 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000013612 plasmid Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 2
- 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 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- 101150096316 5 gene Proteins 0.000 description 2
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 2
- 241000202702 Adeno-associated virus - 3 Species 0.000 description 2
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 2
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 2
- 241001164823 Adeno-associated virus - 7 Species 0.000 description 2
- 241001164825 Adeno-associated virus - 8 Species 0.000 description 2
- 238000012935 Averaging Methods 0.000 description 2
- 102000014914 Carrier Proteins Human genes 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 108091062157 Cis-regulatory element Proteins 0.000 description 2
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 description 2
- 206010064571 Gene mutation Diseases 0.000 description 2
- 102100039289 Glial fibrillary acidic protein Human genes 0.000 description 2
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 2
- -1 Goa Proteins 0.000 description 2
- 102000016285 Guanine Nucleotide Exchange Factors Human genes 0.000 description 2
- 108010067218 Guanine Nucleotide Exchange Factors Proteins 0.000 description 2
- 101000708766 Homo sapiens Structural maintenance of chromosomes protein 3 Proteins 0.000 description 2
- 201000003533 Leber congenital amaurosis Diseases 0.000 description 2
- 102000003792 Metallothionein Human genes 0.000 description 2
- 108090000157 Metallothionein Proteins 0.000 description 2
- 108091022875 Microtubule Proteins 0.000 description 2
- 102000029749 Microtubule Human genes 0.000 description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 208000036448 RPGR-related retinopathy Diseases 0.000 description 2
- 208000004453 Retinal Dysplasia Diseases 0.000 description 2
- 206010038848 Retinal detachment Diseases 0.000 description 2
- 206010057430 Retinal injury Diseases 0.000 description 2
- 206010048955 Retinal toxicity Diseases 0.000 description 2
- 102100040756 Rhodopsin Human genes 0.000 description 2
- 108090000820 Rhodopsin Proteins 0.000 description 2
- 102100029538 Structural maintenance of chromosomes protein 1A Human genes 0.000 description 2
- 102100032723 Structural maintenance of chromosomes protein 3 Human genes 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 201000000467 X-linked cone-rod dystrophy 1 Diseases 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 210000000411 amacrine cell Anatomy 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 230000036755 cellular response Effects 0.000 description 2
- 208000031214 ciliopathy Diseases 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 210000005130 cone cell inner segment Anatomy 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 238000001476 gene delivery Methods 0.000 description 2
- 238000003209 gene knockout Methods 0.000 description 2
- 238000010363 gene targeting Methods 0.000 description 2
- 230000009395 genetic defect Effects 0.000 description 2
- 238000003205 genotyping method Methods 0.000 description 2
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000004807 localization Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 208000002780 macular degeneration Diseases 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 210000004688 microtubule Anatomy 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 230000005043 peripheral vision Effects 0.000 description 2
- 108010079892 phosphoglycerol kinase Proteins 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 239000013608 rAAV vector Substances 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 231100000385 retinal toxicity Toxicity 0.000 description 2
- 201000011574 retinitis pigmentosa 2 Diseases 0.000 description 2
- 210000005078 rod cell inner segment Anatomy 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 210000001324 spliceosome Anatomy 0.000 description 2
- 108010004731 structural maintenance of chromosome protein 1 Proteins 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 230000008189 vertebrate development Effects 0.000 description 2
- 230000003945 visual behavior Effects 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 101150030720 AIPL1 gene Proteins 0.000 description 1
- 208000036443 AIPL1-related retinopathy Diseases 0.000 description 1
- 239000012099 Alexa Fluor family Substances 0.000 description 1
- 108050003620 Arrestin-C Proteins 0.000 description 1
- 102100026440 Arrestin-C Human genes 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- 102100022794 Bestrophin-1 Human genes 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 208000017576 Ciliary body disease Diseases 0.000 description 1
- 102100022641 Coagulation factor IX Human genes 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 208000026372 Congenital cystic kidney disease Diseases 0.000 description 1
- 102100029140 Cyclic nucleotide-gated cation channel beta-3 Human genes 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 239000003298 DNA probe Substances 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000010772 Dog disease Diseases 0.000 description 1
- UPEZCKBFRMILAV-JNEQICEOSA-N Ecdysone Natural products O=C1[C@H]2[C@@](C)([C@@H]3C([C@@]4(O)[C@@](C)([C@H]([C@H]([C@@H](O)CCC(O)(C)C)C)CC4)CC3)=C1)C[C@H](O)[C@H](O)C2 UPEZCKBFRMILAV-JNEQICEOSA-N 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 102000013446 GTP Phosphohydrolases Human genes 0.000 description 1
- 108091006109 GTPases Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000903449 Homo sapiens Bestrophin-1 Proteins 0.000 description 1
- 101000876012 Homo sapiens Conserved oligomeric Golgi complex subunit 4 Proteins 0.000 description 1
- 101000771083 Homo sapiens Cyclic nucleotide-gated cation channel beta-3 Proteins 0.000 description 1
- 101001111338 Homo sapiens Neurofilament heavy polypeptide Proteins 0.000 description 1
- 101000597428 Homo sapiens Nucleoredoxin-like protein 1 Proteins 0.000 description 1
- 101000594760 Homo sapiens Nucleoredoxin-like protein 2 Proteins 0.000 description 1
- 101000712571 Homo sapiens Ras-related protein Rab-8A Proteins 0.000 description 1
- 101001104110 Homo sapiens X-linked retinitis pigmentosa GTPase regulator-interacting protein 1 Proteins 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 101150002793 MYO7A gene Proteins 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 210000005156 Müller Glia Anatomy 0.000 description 1
- 102100024007 Neurofilament heavy polypeptide Human genes 0.000 description 1
- 208000001140 Night Blindness Diseases 0.000 description 1
- 102100022678 Nucleophosmin Human genes 0.000 description 1
- 108010025568 Nucleophosmin Proteins 0.000 description 1
- 102100035399 Nucleoredoxin-like protein 1 Human genes 0.000 description 1
- 102100036205 Nucleoredoxin-like protein 2 Human genes 0.000 description 1
- 101150020891 PRKCA gene Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 102100040375 Peripherin-2 Human genes 0.000 description 1
- 101710135995 Peripherin-2 Proteins 0.000 description 1
- 102100033480 Ras-related protein Rab-8A Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000032430 Retinal dystrophy Diseases 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000006612 Transducin Human genes 0.000 description 1
- 108010087042 Transducin Proteins 0.000 description 1
- BGDKAVGWHJFAGW-UHFFFAOYSA-N Tropicamide Chemical compound C=1C=CC=CC=1C(CO)C(=O)N(CC)CC1=CC=NC=C1 BGDKAVGWHJFAGW-UHFFFAOYSA-N 0.000 description 1
- 208000014769 Usher Syndromes Diseases 0.000 description 1
- 241001492404 Woodchuck hepatitis virus Species 0.000 description 1
- 208000028321 X-linked cone-rod dystrophy Diseases 0.000 description 1
- 102100040089 X-linked retinitis pigmentosa GTPase regulator-interacting protein 1 Human genes 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- UPEZCKBFRMILAV-UHFFFAOYSA-N alpha-Ecdysone Natural products C1C(O)C(O)CC2(C)C(CCC3(C(C(C(O)CCC(C)(C)O)C)CCC33O)C)C3=CC(=O)C21 UPEZCKBFRMILAV-UHFFFAOYSA-N 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 210000003986 cell retinal photoreceptor Anatomy 0.000 description 1
- 210000004718 centriole Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000004081 cilia Anatomy 0.000 description 1
- 210000004240 ciliary body Anatomy 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 201000006754 cone-rod dystrophy Diseases 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 238000009223 counseling Methods 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 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 1
- 230000005750 disease progression Effects 0.000 description 1
- BFMYDTVEBKDAKJ-UHFFFAOYSA-L disodium;(2',7'-dibromo-3',6'-dioxido-3-oxospiro[2-benzofuran-1,9'-xanthene]-4'-yl)mercury;hydrate Chemical compound O.[Na+].[Na+].O1C(=O)C2=CC=CC=C2C21C1=CC(Br)=C([O-])C([Hg])=C1OC1=C2C=C(Br)C([O-])=C1 BFMYDTVEBKDAKJ-UHFFFAOYSA-L 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- UPEZCKBFRMILAV-JMZLNJERSA-N ecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@H]([C@H](O)CCC(C)(C)O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 UPEZCKBFRMILAV-JMZLNJERSA-N 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000013742 energy transducer activity Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229940049268 euthasol Drugs 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 208000009429 hemophilia B Diseases 0.000 description 1
- 230000003118 histopathologic effect Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 230000004298 light response Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 201000002648 nephronophthisis Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000004297 night vision Effects 0.000 description 1
- 238000002577 ophthalmoscopy Methods 0.000 description 1
- 210000003733 optic disk Anatomy 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000016732 phototransduction Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 238000013326 plasmid cotransfection Methods 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 238000005036 potential barrier Methods 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 101150066583 rep gene Proteins 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 238000007894 restriction fragment length polymorphism technique Methods 0.000 description 1
- 210000003660 reticulum Anatomy 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 210000003994 retinal ganglion cell Anatomy 0.000 description 1
- 230000004281 retinal morphology Effects 0.000 description 1
- 230000004286 retinal pathology Effects 0.000 description 1
- 239000000790 retinal pigment Substances 0.000 description 1
- 230000004268 retinal thickening Effects 0.000 description 1
- 210000001210 retinal vessel Anatomy 0.000 description 1
- 201000011575 retinitis pigmentosa 3 Diseases 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 210000004358 rod cell outer segment Anatomy 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 108010079094 short-wavelength opsin Proteins 0.000 description 1
- 230000037432 silent mutation Effects 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 238000013520 translational research Methods 0.000 description 1
- 229960004791 tropicamide Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 230000004382 visual function Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K38/46—Hydrolases (3)
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/185—Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
-
- 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
-
- 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
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y306/00—Hydrolases acting on acid anhydrides (3.6)
- C12Y306/05—Hydrolases acting on acid anhydrides (3.6) acting on GTP; involved in cellular and subcellular movement (3.6.5)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Psychology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Marine Sciences & Fisheries (AREA)
- Toxicology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Plant Pathology (AREA)
- Virology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Ophthalmology & Optometry (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261670355P | 2012-07-11 | 2012-07-11 | |
| US61/670,355 | 2012-07-11 | ||
| PCT/US2013/022628 WO2014011210A1 (en) | 2012-07-11 | 2013-01-23 | Aav-mediated gene therapy for rpgr x-linked retinal degeneration |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105120901A true CN105120901A (zh) | 2015-12-02 |
Family
ID=49916455
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201380045636.1A Pending CN105120901A (zh) | 2012-07-11 | 2013-01-23 | Rpgr x染色体连锁视网膜退化的aav介导的基因治疗 |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US9770491B2 (enExample) |
| EP (1) | EP2872183B1 (enExample) |
| JP (1) | JP6199965B2 (enExample) |
| CN (1) | CN105120901A (enExample) |
| AU (1) | AU2013287281B2 (enExample) |
| CA (1) | CA2878171C (enExample) |
| NZ (1) | NZ704275A (enExample) |
| WO (1) | WO2014011210A1 (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115243766A (zh) * | 2020-02-28 | 2022-10-25 | 宾夕法尼亚州大学信托人 | 治疗常染色体显性bestrophin病及其评估方法 |
| CN117050951A (zh) * | 2023-08-24 | 2023-11-14 | 广州医药研究总院有限公司 | X连锁视网膜色素变性模型犬的构建方法 |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2878171C (en) * | 2012-07-11 | 2021-04-27 | The Trustees Of The University Of Pennsylvania | Aav-mediated gene therapy for rpgr x-linked retinal degeneration |
| ES2760263T3 (es) * | 2014-03-21 | 2020-05-13 | Genzyme Corp | Tratamiento génico de la retinitis pigmentaria |
| JP6635942B2 (ja) * | 2014-04-15 | 2020-01-29 | アプライド ジェネティック テクノロジーズ コーポレイション | 網膜色素変性症ｇｔｐアーゼレギュレーター（ｒｐｇｒ）をコードするコドン最適化核酸 |
| GB201412011D0 (en) * | 2014-07-04 | 2014-08-20 | Ucl Business Plc | Treatments |
| SMT202000715T1 (it) * | 2014-07-24 | 2021-01-05 | Massachusetts Eye & Ear Infirmary | Terapia genica rpgr per la retinite pigmentosa |
| EP3748007B1 (en) * | 2015-03-06 | 2024-06-26 | Massachusetts Eye & Ear Infirmary | Gene augmentation therapies for inherited retinal degeneration caused by mutations in the prpf31 gene |
| EP3719134B1 (en) * | 2015-03-11 | 2023-08-23 | The United States of America, as represented by The Secretary, Department of Health and Human Services | Rp2 vectors for treating x-linked retinitis pigmentosa |
| WO2016193434A1 (en) * | 2015-06-04 | 2016-12-08 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Improved methods for treating ocular diseases by gene therapy |
| GB201516066D0 (en) | 2015-09-10 | 2015-10-28 | Young & Co Llp D | Treatment of retinitis pigmentosa |
| WO2017087900A1 (en) | 2015-11-19 | 2017-05-26 | The Trustees Of The University Of Pennsylvania | Compositions and methods for correction of heritable ocular disease |
| EP3389724B1 (en) | 2015-12-14 | 2020-07-01 | The Trustees Of The University Of Pennsylvania | Gene therapy for ocular disorders |
| CN109661470A (zh) | 2016-04-15 | 2019-04-19 | 宾夕法尼亚州大学信托人 | 新型aav8突变衣壳和含有其的组合物 |
| EP3481958A4 (en) | 2016-07-08 | 2019-12-25 | The Trustees of The University of Pennsylvania | METHOD AND COMPOSITIONS FOR TREATING DISTURBANCES AND DISEASES WITH RDH12 |
| CN119752819A (zh) | 2017-03-01 | 2025-04-04 | 宾夕法尼亚州立大学托管会 | 用于眼部病症的基因疗法 |
| WO2018200542A1 (en) | 2017-04-24 | 2018-11-01 | The Trustees Of The University Of Pennsylvania | Gene therapy for ocular disorders |
| WO2018218359A1 (en) | 2017-05-31 | 2018-12-06 | The Trustees Of The University Of Pennsylvania | Gene therapy for treating peroxisomal disorders |
| EP3638316A4 (en) | 2017-06-14 | 2021-03-24 | The Trustees Of The University Of Pennsylvania | GENE THERAPY FOR EYE DISEASES |
| AU2018367606B2 (en) * | 2017-11-15 | 2024-08-29 | The Regents Of The University Of Michigan | Viral vectors comprising RDH12 coding regions and methods of treating retinal dystrophies |
| KR102866133B1 (ko) | 2018-04-17 | 2025-09-30 | 더 트러스티스 오브 더 유니버시티 오브 펜실바니아 | 트랜스-스플라이싱 분자 |
| WO2020061528A1 (en) | 2018-09-21 | 2020-03-26 | University Of Connecticut | Compositions and methods to restore paternal ube3a gene expression in human angelman syndrome |
| CA3131023A1 (en) * | 2019-02-22 | 2020-08-27 | Michael R. Volkert | Oxr1 gene therapy |
| CN113952472A (zh) * | 2020-07-21 | 2022-01-21 | 英斯培瑞有限公司 | 用于治疗眼部疾病的组合物和方法 |
| EP4208156A4 (en) | 2020-09-02 | 2025-01-15 | 4D Molecular Therapeutics Inc. | CODON-OPTIMIZED RPGRRF-15 GENES AND USES THEREOF |
| EP4284335A1 (en) | 2021-02-01 | 2023-12-06 | RegenxBio Inc. | Gene therapy for neuronal ceroid lipofuscinoses |
| WO2023220742A2 (en) | 2022-05-13 | 2023-11-16 | Ascidian Therapeutics, Inc. | Abca4 trans-splicing molecules |
| CN117165596A (zh) * | 2022-05-27 | 2023-12-05 | 武汉纽福斯生物科技有限公司 | 编码rpgr的核酸及其应用 |
| IL318200A (en) * | 2022-07-14 | 2025-03-01 | Fond Asile Des Aveugles | Gene therapy for FAM161A-related retinopathies and other ciliopathies |
| US12252518B2 (en) | 2023-01-06 | 2025-03-18 | Life Biosciences, Inc. | Methods of treating non-arteritic anterior ischemic optic neuropathy |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5478745A (en) | 1992-12-04 | 1995-12-26 | University Of Pittsburgh | Recombinant viral vector system |
| US5939534A (en) | 1993-12-29 | 1999-08-17 | Sumitomo Pharmaceuticals Company, Limited | Factors mutated in the D1 cap region |
| JP3768257B2 (ja) * | 1993-12-29 | 2006-04-19 | 大日本住友製薬株式会社 | 改変タンパク質 |
| US6372250B1 (en) * | 2000-04-25 | 2002-04-16 | The Regents Of The University Of California | Non-invasive gene targeting to the brain |
| EP1381276A4 (en) | 2001-04-13 | 2005-02-02 | Univ Pennsylvania | METHOD FOR TREATMENT OR DEVELOPMENT SLUDGE DEGRADATION |
| US20030003582A1 (en) | 2001-05-08 | 2003-01-02 | Tranzyme, Inc. | Trans-viral vector mediated gene transfer to the retina |
| ES2602352T3 (es) | 2001-12-17 | 2017-02-20 | The Trustees Of The University Of Pennsylvania | Secuencias de serotipo 8 de virus adenoasociado (VAA), vectores que las contienen y usos de las mismas |
| DK2311848T3 (da) | 2002-12-23 | 2013-10-14 | Vical Inc | Kodon-optimerede polynukleotidbaserede vacciner mod human cytomegalovirus-infektion |
| EP1486567A1 (en) | 2003-06-11 | 2004-12-15 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Improved adeno-associated virus (AAV) vector for gene therapy |
| EP2298926A1 (en) | 2003-09-30 | 2011-03-23 | The Trustees of The University of Pennsylvania | Adeno-associated virus (AAV) clades, sequences, vectors containing same, and uses thereof |
| ES2331342B1 (es) | 2006-05-22 | 2010-10-13 | Consejo Superior Investg.Cientificas | Uso de la proinsulina para la elaboracion de una composicion farmaceutica neuroprotectora, composicion terapeutica que la contiene y sus aplicaciones. |
| AU2009212309B2 (en) * | 2008-02-07 | 2014-04-03 | Ceregene, Inc. | Rescue of photoreceptors by intravitreal administration of an expression vector encoding a therapeutic protein |
| US20100081707A1 (en) * | 2008-02-21 | 2010-04-01 | Ali Robin R | Devices and methods for delivering polynucleotides into retinal cells of the macula and fovea |
| US7561973B1 (en) | 2008-07-31 | 2009-07-14 | Dna Twopointo, Inc. | Methods for determining properties that affect an expression property value of polynucleotides in an expression system |
| US7561972B1 (en) | 2008-06-06 | 2009-07-14 | Dna Twopointo, Inc. | Synthetic nucleic acids for expression of encoded proteins |
| ITMI20090284A1 (it) | 2009-02-26 | 2010-08-27 | Consiglio Nazionale Ricerche | Uso di inibitori della serina palmitoiltrasferasi per la prevenzione e il rallentamento delle degenerazioni retiniche ereditarie e relative composizioni |
| GB0911870D0 (en) * | 2009-07-08 | 2009-08-19 | Ucl Business Plc | Optimised coding sequence and promoter |
| CA2878171C (en) * | 2012-07-11 | 2021-04-27 | The Trustees Of The University Of Pennsylvania | Aav-mediated gene therapy for rpgr x-linked retinal degeneration |
-
2013
- 2013-01-23 CA CA2878171A patent/CA2878171C/en active Active
- 2013-01-23 NZ NZ704275A patent/NZ704275A/en unknown
- 2013-01-23 JP JP2015521593A patent/JP6199965B2/ja active Active
- 2013-01-23 WO PCT/US2013/022628 patent/WO2014011210A1/en not_active Ceased
- 2013-01-23 AU AU2013287281A patent/AU2013287281B2/en active Active
- 2013-01-23 US US14/413,884 patent/US9770491B2/en active Active
- 2013-01-23 CN CN201380045636.1A patent/CN105120901A/zh active Pending
- 2013-01-23 EP EP13816245.8A patent/EP2872183B1/en active Active
-
2017
- 2017-09-08 US US15/699,262 patent/US10383922B2/en active Active
Non-Patent Citations (4)
| Title |
|---|
| BELTRAN W A ET AL: "Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa", 《PNAS》 * |
| HONG D H ET AL: "A single, abbreviated RPGR-ORF15 variant reconstitutes RPGR function in vivo", 《IOVS》 * |
| NATKUNARAJAH M ET AL: "AAV mediated gene replacement therapy in the RPGR knockout mouse-a model of X-linked retinitis pigmentosa", 《IOVS》 * |
| 单清 等: "病毒载体介导的视网膜基因转移研究进展", 《眼科研究》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115243766A (zh) * | 2020-02-28 | 2022-10-25 | 宾夕法尼亚州大学信托人 | 治疗常染色体显性bestrophin病及其评估方法 |
| CN117050951A (zh) * | 2023-08-24 | 2023-11-14 | 广州医药研究总院有限公司 | X连锁视网膜色素变性模型犬的构建方法 |
| CN117050951B (zh) * | 2023-08-24 | 2024-06-04 | 广州医药研究总院有限公司 | X连锁视网膜色素变性模型犬的构建方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2014011210A1 (en) | 2014-01-16 |
| US20150202269A1 (en) | 2015-07-23 |
| JP2015523379A (ja) | 2015-08-13 |
| US10383922B2 (en) | 2019-08-20 |
| AU2013287281A1 (en) | 2015-02-19 |
| CA2878171C (en) | 2021-04-27 |
| NZ704275A (en) | 2016-09-30 |
| AU2013287281B2 (en) | 2018-04-26 |
| US9770491B2 (en) | 2017-09-26 |
| EP2872183A1 (en) | 2015-05-20 |
| JP6199965B2 (ja) | 2017-09-20 |
| EP2872183B1 (en) | 2018-09-26 |
| EP2872183A4 (en) | 2015-12-09 |
| US20180036385A1 (en) | 2018-02-08 |
| CA2878171A1 (en) | 2014-01-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US10383922B2 (en) | AAV-mediated gene therapy for RPGR X-linked retinal degeneration | |
| JP7572990B2 (ja) | Ｒｄｈ１２が関与する疾患及び疾病を治療する方法及び組成物 | |
| JP7766393B2 (ja) | 眼疾患のための遺伝子療法 | |
| JP7671790B2 (ja) | 眼疾患の遺伝子治療 | |
| US11793887B2 (en) | Gene therapy for treating peroxisomal disorders | |
| CN113795279B (zh) | 靶向akt通路的神经保护性基因疗法 | |
| HK40013460A (en) | Methods and compositions for treatment of disorders and diseases involving rdh12 | |
| HK40013460B (zh) | 用於治疗涉及rdh12的病症和疾病的方法和组合物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20151202 |