CA2713755A1 - Rescue of photoreceptors by intravitreal administration of an expression vector encoding a therapeutic protein - Google Patents
Rescue of photoreceptors by intravitreal administration of an expression vector encoding a therapeutic protein Download PDFInfo
- Publication number
- CA2713755A1 CA2713755A1 CA2713755A CA2713755A CA2713755A1 CA 2713755 A1 CA2713755 A1 CA 2713755A1 CA 2713755 A CA2713755 A CA 2713755A CA 2713755 A CA2713755 A CA 2713755A CA 2713755 A1 CA2713755 A1 CA 2713755A1
- Authority
- CA
- Canada
- Prior art keywords
- cells
- aav
- vector
- growth factor
- retina
- 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.)
- Abandoned
Links
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 62
- 108091008695 photoreceptors Proteins 0.000 title claims abstract description 52
- 239000013604 expression vector Substances 0.000 title claims abstract description 32
- 102000004169 proteins and genes Human genes 0.000 title abstract description 39
- 230000001225 therapeutic effect Effects 0.000 title abstract description 9
- 210000004027 cell Anatomy 0.000 claims abstract description 128
- 210000001525 retina Anatomy 0.000 claims abstract description 73
- 239000013598 vector Substances 0.000 claims abstract description 49
- 238000000034 method Methods 0.000 claims abstract description 47
- 239000003102 growth factor Substances 0.000 claims abstract description 38
- 210000003994 retinal ganglion cell Anatomy 0.000 claims abstract description 29
- 208000022873 Ocular disease Diseases 0.000 claims abstract description 27
- 230000002207 retinal effect Effects 0.000 claims abstract description 27
- 238000011065 in-situ storage Methods 0.000 claims abstract description 13
- 238000003259 recombinant expression Methods 0.000 claims abstract description 9
- 150000007523 nucleic acids Chemical group 0.000 claims description 50
- 230000014509 gene expression Effects 0.000 claims description 42
- 238000002347 injection Methods 0.000 claims description 37
- 239000007924 injection Substances 0.000 claims description 37
- 230000007850 degeneration Effects 0.000 claims description 32
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims description 26
- 108010025020 Nerve Growth Factor Proteins 0.000 claims description 20
- 230000004044 response Effects 0.000 claims description 20
- 208000002780 macular degeneration Diseases 0.000 claims description 16
- 239000013607 AAV vector Substances 0.000 claims description 15
- 210000000608 photoreceptor cell Anatomy 0.000 claims description 14
- 210000000880 retinal rod photoreceptor cell Anatomy 0.000 claims description 12
- 210000005156 Müller Glia Anatomy 0.000 claims description 10
- 210000000964 retinal cone photoreceptor cell Anatomy 0.000 claims description 10
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 claims description 9
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 claims description 9
- 208000015181 infectious disease Diseases 0.000 claims description 9
- 229940053128 nerve growth factor Drugs 0.000 claims description 9
- 102000015336 Nerve Growth Factor Human genes 0.000 claims description 8
- 238000002513 implantation Methods 0.000 claims description 8
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 claims description 7
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 claims description 7
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 6
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 claims description 5
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 claims description 5
- 210000002287 horizontal cell Anatomy 0.000 claims description 4
- 230000003076 paracrine Effects 0.000 claims description 4
- 229940127291 Calcium channel antagonist Drugs 0.000 claims description 2
- 108010067390 Viral Proteins Proteins 0.000 claims description 2
- 239000000480 calcium channel blocker Substances 0.000 claims description 2
- 210000001127 pigmented epithelial cell Anatomy 0.000 claims description 2
- 108090000099 Neurotrophin-4 Proteins 0.000 abstract description 107
- 102000003683 Neurotrophin-4 Human genes 0.000 abstract description 105
- 229940097998 neurotrophin 4 Drugs 0.000 abstract description 100
- 238000011282 treatment Methods 0.000 abstract description 12
- 238000012546 transfer Methods 0.000 abstract description 7
- 230000008685 targeting Effects 0.000 abstract description 6
- 210000001508 eye Anatomy 0.000 description 67
- 108020004707 nucleic acids Proteins 0.000 description 47
- 102000039446 nucleic acids Human genes 0.000 description 47
- 239000010410 layer Substances 0.000 description 35
- 102000001839 Neurturin Human genes 0.000 description 28
- 108010015406 Neurturin Proteins 0.000 description 28
- 206010029113 Neovascularisation Diseases 0.000 description 20
- 241000700159 Rattus Species 0.000 description 18
- 239000012537 formulation buffer Substances 0.000 description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 15
- 238000005259 measurement Methods 0.000 description 15
- 230000008832 photodamage Effects 0.000 description 15
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 14
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 14
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 14
- 201000007737 Retinal degeneration Diseases 0.000 description 13
- 102000007072 Nerve Growth Factors Human genes 0.000 description 12
- 230000004258 retinal degeneration Effects 0.000 description 12
- 210000001519 tissue Anatomy 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 10
- 230000002159 abnormal effect Effects 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 230000003612 virological effect Effects 0.000 description 10
- 241000282472 Canis lupus familiaris Species 0.000 description 9
- 230000001404 mediated effect Effects 0.000 description 9
- 210000002569 neuron Anatomy 0.000 description 9
- 239000003981 vehicle Substances 0.000 description 9
- 101150115477 Vldlr gene Proteins 0.000 description 8
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 230000001105 regulatory effect Effects 0.000 description 8
- 230000002103 transcriptional effect Effects 0.000 description 8
- 241000239290 Araneae Species 0.000 description 7
- 230000036541 health Effects 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 238000011824 transgenic rat model Methods 0.000 description 7
- 241000282412 Homo Species 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 108090000820 Rhodopsin Proteins 0.000 description 6
- 108700019146 Transgenes Proteins 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- 239000013612 plasmid Substances 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 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 5
- 102000004330 Rhodopsin Human genes 0.000 description 5
- 230000005856 abnormality Effects 0.000 description 5
- 230000035772 mutation Effects 0.000 description 5
- 201000007790 vitelliform macular dystrophy Diseases 0.000 description 5
- 241000702421 Dependoparvovirus Species 0.000 description 4
- 208000036142 Viral infection Diseases 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 230000004456 color vision Effects 0.000 description 4
- 201000006754 cone-rod dystrophy Diseases 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000011833 dog model Methods 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 230000004770 neurodegeneration Effects 0.000 description 4
- 239000003900 neurotrophic factor Substances 0.000 description 4
- 230000004792 oxidative damage Effects 0.000 description 4
- 230000004224 protection Effects 0.000 description 4
- 238000011552 rat model Methods 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 238000001890 transfection Methods 0.000 description 4
- 238000011830 transgenic mouse model Methods 0.000 description 4
- 230000009385 viral infection Effects 0.000 description 4
- 208000002691 Choroiditis Diseases 0.000 description 3
- 241000701022 Cytomegalovirus Species 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- 208000003098 Ganglion Cysts Diseases 0.000 description 3
- 101000609947 Homo sapiens Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha Proteins 0.000 description 3
- 206010025412 Macular dystrophy congenital Diseases 0.000 description 3
- 208000003971 Posterior uveitis Diseases 0.000 description 3
- 208000007135 Retinal Neovascularization Diseases 0.000 description 3
- 102100039177 Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha Human genes 0.000 description 3
- 208000005400 Synovial Cyst Diseases 0.000 description 3
- 206010043189 Telangiectasia Diseases 0.000 description 3
- 206010052428 Wound Diseases 0.000 description 3
- 150000001413 amino acids Chemical group 0.000 description 3
- 239000004037 angiogenesis inhibitor Substances 0.000 description 3
- 230000001772 anti-angiogenic effect Effects 0.000 description 3
- 210000001130 astrocyte Anatomy 0.000 description 3
- 210000000981 epithelium Anatomy 0.000 description 3
- 230000004438 eyesight Effects 0.000 description 3
- 210000002592 gangliocyte Anatomy 0.000 description 3
- 210000005260 human cell Anatomy 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 230000000324 neuroprotective effect Effects 0.000 description 3
- 210000003733 optic disk Anatomy 0.000 description 3
- 210000001328 optic nerve Anatomy 0.000 description 3
- 230000036542 oxidative stress Effects 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 230000004243 retinal function Effects 0.000 description 3
- 102200141512 rs104893768 Human genes 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 210000000130 stem cell Anatomy 0.000 description 3
- 208000009056 telangiectasis Diseases 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000009261 transgenic effect Effects 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- 230000010415 tropism Effects 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- 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 2
- WLCZTRVUXYALDD-IBGZPJMESA-N 7-[[(2s)-2,6-bis(2-methoxyethoxycarbonylamino)hexanoyl]amino]heptoxy-methylphosphinic acid Chemical compound COCCOC(=O)NCCCC[C@H](NC(=O)OCCOC)C(=O)NCCCCCCCOP(C)(O)=O WLCZTRVUXYALDD-IBGZPJMESA-N 0.000 description 2
- 208000036443 AIPL1-related retinopathy Diseases 0.000 description 2
- 201000001321 Bardet-Biedl syndrome Diseases 0.000 description 2
- 208000037663 Best vitelliform macular dystrophy Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 108010035563 Chloramphenicol O-acetyltransferase Proteins 0.000 description 2
- 208000033810 Choroidal dystrophy Diseases 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 description 2
- 201000001353 Doyne honeycomb retinal dystrophy Diseases 0.000 description 2
- 206010058314 Dysplasia Diseases 0.000 description 2
- 208000037312 Familial drusen Diseases 0.000 description 2
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 2
- 208000010412 Glaucoma Diseases 0.000 description 2
- 101000996663 Homo sapiens Neurotrophin-4 Proteins 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 2
- 102100025947 Insulin-like growth factor II Human genes 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 206010056715 Laurence-Moon-Bardet-Biedl syndrome Diseases 0.000 description 2
- 201000003533 Leber congenital amaurosis Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- -1 NRP-1 Proteins 0.000 description 2
- 229930193140 Neomycin Natural products 0.000 description 2
- 102000004230 Neurotrophin 3 Human genes 0.000 description 2
- 108090000742 Neurotrophin 3 Proteins 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 102000010175 Opsin Human genes 0.000 description 2
- 108050001704 Opsin Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 208000005587 Refsum Disease Diseases 0.000 description 2
- 206010038848 Retinal detachment Diseases 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038910 Retinitis Diseases 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 208000027073 Stargardt disease Diseases 0.000 description 2
- 102000011923 Thyrotropin Human genes 0.000 description 2
- 108010061174 Thyrotropin Proteins 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 208000014769 Usher Syndromes Diseases 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 208000030597 adult Refsum disease Diseases 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000006727 cell loss Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 210000003161 choroid Anatomy 0.000 description 2
- 208000003571 choroideremia Diseases 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 230000002596 correlated effect Effects 0.000 description 2
- ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000009395 genetic defect Effects 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000001524 infective effect Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 229940092110 macugen Drugs 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 229960004927 neomycin Drugs 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 229940032018 neurotrophin 3 Drugs 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 230000004264 retinal detachment Effects 0.000 description 2
- 210000001210 retinal vessel Anatomy 0.000 description 2
- 201000007714 retinoschisis Diseases 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 229960000874 thyrotropin Drugs 0.000 description 2
- 230000001748 thyrotropin Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000002054 transplantation Methods 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 208000020938 vitelliform macular dystrophy 2 Diseases 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- CQOQDQWUFQDJMK-SSTWWWIQSA-N 2-methoxy-17beta-estradiol Chemical compound C([C@@H]12)C[C@]3(C)[C@@H](O)CC[C@H]3[C@@H]1CCC1=C2C=C(OC)C(O)=C1 CQOQDQWUFQDJMK-SSTWWWIQSA-N 0.000 description 1
- SGOOQMRIPALTEL-UHFFFAOYSA-N 4-hydroxy-N,1-dimethyl-2-oxo-N-phenyl-3-quinolinecarboxamide Chemical compound OC=1C2=CC=CC=C2N(C)C(=O)C=1C(=O)N(C)C1=CC=CC=C1 SGOOQMRIPALTEL-UHFFFAOYSA-N 0.000 description 1
- 208000024810 Abnormal retinal morphology Diseases 0.000 description 1
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 1
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 1
- 102000052866 Amino Acyl-tRNA Synthetases Human genes 0.000 description 1
- 108700028939 Amino Acyl-tRNA Synthetases Proteins 0.000 description 1
- 102100034608 Angiopoietin-2 Human genes 0.000 description 1
- 108010048036 Angiopoietin-2 Proteins 0.000 description 1
- 102400000068 Angiostatin Human genes 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- 102000004411 Antithrombin III Human genes 0.000 description 1
- 108090000935 Antithrombin III Proteins 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 102100027106 BRCA1-associated protein Human genes 0.000 description 1
- 101710196510 BRCA1-associated protein Proteins 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 101100208237 Bos taurus THBS2 gene Proteins 0.000 description 1
- 102000004082 Calreticulin Human genes 0.000 description 1
- 108090000549 Calreticulin Proteins 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 102400000730 Canstatin Human genes 0.000 description 1
- 101800000626 Canstatin Proteins 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 102100031186 Chromogranin-A Human genes 0.000 description 1
- 102100024484 Codanin-1 Human genes 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 1
- 206010051559 Corneal defect Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000938605 Crocodylia Species 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 206010012305 Demyelination Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 1
- 206010013774 Dry eye Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102400001047 Endostatin Human genes 0.000 description 1
- 108010079505 Endostatins Proteins 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- 208000003492 Fundus albipunctatus Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 206010018341 Gliosis Diseases 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 208000007698 Gyrate Atrophy Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 208000003923 Hereditary Corneal Dystrophies Diseases 0.000 description 1
- 208000028782 Hereditary disease Diseases 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 208000029433 Herpesviridae infectious disease Diseases 0.000 description 1
- 101000980888 Homo sapiens Codanin-1 Proteins 0.000 description 1
- 101001108441 Homo sapiens Neurturin Proteins 0.000 description 1
- 101000830596 Homo sapiens Tumor necrosis factor ligand superfamily member 15 Proteins 0.000 description 1
- 101000666934 Homo sapiens Very low-density lipoprotein receptor Proteins 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 239000000854 Human Growth Hormone Substances 0.000 description 1
- 235000003332 Ilex aquifolium Nutrition 0.000 description 1
- 241000209027 Ilex aquifolium Species 0.000 description 1
- 101710144867 Inositol monophosphatase Proteins 0.000 description 1
- 102100021244 Integral membrane protein GPR180 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 108090000171 Interleukin-18 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 206010022941 Iridocyclitis Diseases 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 208000015439 Lysosomal storage disease Diseases 0.000 description 1
- 208000008955 Mucolipidoses Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101000686934 Mus musculus Prolactin-7D1 Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029174 Nerve compression Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000001140 Night Blindness Diseases 0.000 description 1
- 208000025464 Norrie disease Diseases 0.000 description 1
- MSHZHSPISPJWHW-UHFFFAOYSA-N O-(chloroacetylcarbamoyl)fumagillol Chemical compound O1C(CC=C(C)C)C1(C)C1C(OC)C(OC(=O)NC(=O)CCl)CCC21CO2 MSHZHSPISPJWHW-UHFFFAOYSA-N 0.000 description 1
- 208000014245 Ocular vascular disease Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 101710131036 Opsin-1 Proteins 0.000 description 1
- 102000004264 Osteopontin Human genes 0.000 description 1
- 108010081689 Osteopontin Proteins 0.000 description 1
- 101150059127 Pde6a gene Proteins 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 102000004211 Platelet factor 4 Human genes 0.000 description 1
- 108090000778 Platelet factor 4 Proteins 0.000 description 1
- 241001085205 Prenanthella exigua Species 0.000 description 1
- 102100024819 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 102100027378 Prothrombin Human genes 0.000 description 1
- 108010094028 Prothrombin Proteins 0.000 description 1
- 208000036891 RDH5-related retinopathy Diseases 0.000 description 1
- 208000036903 RLBP1-related retinopathy Diseases 0.000 description 1
- 108091008103 RNA aptamers Proteins 0.000 description 1
- 238000010240 RT-PCR analysis Methods 0.000 description 1
- 102400001051 Restin Human genes 0.000 description 1
- 206010057430 Retinal injury Diseases 0.000 description 1
- 208000014633 Retinitis punctata albescens Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 206010038997 Retroviral infections Diseases 0.000 description 1
- 108010005173 SERPIN-B5 Proteins 0.000 description 1
- 102100030333 Serpin B5 Human genes 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 208000018440 Superficial corneal dystrophy Diseases 0.000 description 1
- 102400000709 T2-TrpRS Human genes 0.000 description 1
- 101800000458 T2-TrpRS Proteins 0.000 description 1
- 102000002938 Thrombospondin Human genes 0.000 description 1
- 108060008245 Thrombospondin Proteins 0.000 description 1
- 108010046722 Thrombospondin 1 Proteins 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 102100024587 Tumor necrosis factor ligand superfamily member 15 Human genes 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010064996 Ulcerative keratitis Diseases 0.000 description 1
- 102000016548 Vascular Endothelial Growth Factor Receptor-1 Human genes 0.000 description 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 1
- 102100039066 Very low-density lipoprotein receptor Human genes 0.000 description 1
- 241000700605 Viruses Species 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
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 208000002205 allergic conjunctivitis Diseases 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 210000000411 amacrine cell Anatomy 0.000 description 1
- 230000037354 amino acid metabolism Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 201000004612 anterior uveitis Diseases 0.000 description 1
- 238000011122 anti-angiogenic therapy Methods 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 229960005348 antithrombin iii Drugs 0.000 description 1
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
- 208000037875 astrocytosis Diseases 0.000 description 1
- 230000007341 astrogliosis Effects 0.000 description 1
- 208000024998 atopic conjunctivitis Diseases 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 210000000467 autonomic pathway Anatomy 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 208000036338 butterfly-shaped pigment dystrophy Diseases 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 210000003986 cell retinal photoreceptor Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 210000004240 ciliary body Anatomy 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 108010038764 cytoplasmic linker protein 170 Proteins 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000007877 drug screening Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000001493 electron microscopy Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000010230 functional analysis Methods 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 208000007345 glycogen storage disease Diseases 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 102000052667 human NRTN Human genes 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000006058 immune tolerance Effects 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 208000023343 iris disease Diseases 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000011866 long-term treatment Methods 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
- 230000036244 malformation Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000003771 matrix metalloproteinase inhibitor Substances 0.000 description 1
- 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 description 1
- 239000002923 metal particle Substances 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 210000003061 neural cell Anatomy 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 230000003955 neuronal function Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 230000000508 neurotrophic effect Effects 0.000 description 1
- 230000004297 night vision Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 208000014380 ornithine aminotransferase deficiency Diseases 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000007427 paired t-test Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 230000005043 peripheral vision Effects 0.000 description 1
- 231100000760 phototoxic Toxicity 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 208000017711 posterior corneal dystrophy Diseases 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 229940039716 prothrombin Drugs 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 239000013608 rAAV vector Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000004263 retinal angiogenesis Effects 0.000 description 1
- 210000001116 retinal neuron Anatomy 0.000 description 1
- 239000000790 retinal pigment Substances 0.000 description 1
- 210000001164 retinal progenitor cell Anatomy 0.000 description 1
- 230000004233 retinal vasculature Effects 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 229960003522 roquinimex Drugs 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 210000003863 superior colliculi Anatomy 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 1
- 229960005314 suramin Drugs 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 238000012301 transgenic model Methods 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 231100000216 vascular lesion Toxicity 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 108010060757 vasostatin Proteins 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 230000004382 visual function Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 230000004400 visual pathway Effects 0.000 description 1
- 210000000239 visual pathway Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- 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
- 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
- A61K48/0075—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 delivery route, e.g. oral, subcutaneous
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
- A61K9/0051—Ocular inserts, ocular implants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2799/00—Uses of viruses
- C12N2799/02—Uses of viruses as vector
- C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid
- C12N2799/025—Uses of viruses as vector for the expression of a heterologous nucleic acid where the vector is derived from a parvovirus
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychology (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Immunology (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 (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2699008P | 2008-02-07 | 2008-02-07 | |
| US61/026,990 | 2008-02-07 | ||
| US9322808P | 2008-08-29 | 2008-08-29 | |
| US61/093,228 | 2008-08-29 | ||
| PCT/US2009/033275 WO2009100253A1 (en) | 2008-02-07 | 2009-02-05 | Rescue of photoreceptors by intravitreal administation of an expression vector encoding a therapeutic protein |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2713755A1 true CA2713755A1 (en) | 2009-08-13 |
Family
ID=40939054
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2713755A Abandoned CA2713755A1 (en) | 2008-02-07 | 2009-02-05 | Rescue of photoreceptors by intravitreal administration of an expression vector encoding a therapeutic protein |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US8242093B2 (OSRAM) |
| EP (1) | EP2247258A4 (OSRAM) |
| JP (1) | JP2011511090A (OSRAM) |
| CN (1) | CN101980668A (OSRAM) |
| AU (1) | AU2009212309B2 (OSRAM) |
| CA (1) | CA2713755A1 (OSRAM) |
| WO (1) | WO2009100253A1 (OSRAM) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2009212309B2 (en) * | 2008-02-07 | 2014-04-03 | Ceregene, Inc. | Rescue of photoreceptors by intravitreal administration of an expression vector encoding a therapeutic protein |
| GB201103062D0 (en) * | 2011-02-22 | 2011-04-06 | Isis Innovation | Method |
| SG10201704505TA (en) * | 2011-02-25 | 2017-06-29 | Riken | Method of producing retinal pigment epithelial cell sheet |
| JP6199965B2 (ja) | 2012-07-11 | 2017-09-20 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | Ｒｐｇｒｘ連鎖性網膜変性のａａｖ媒介型遺伝子治療 |
| US20160256571A1 (en) * | 2013-09-30 | 2016-09-08 | Sanofi | Invention |
| MA39082B2 (fr) * | 2013-12-06 | 2021-11-30 | Inst Nat Sante Rech Med | Méthodes et compositions pharmaceutiques pour exprimer un polynucléotide d'intérêt dans l'épithélium pigmentaire rétinien d'un sujet |
| CA2982213C (en) * | 2015-04-09 | 2022-10-18 | Cornell University | Gene therapy to prevent reactions to allergens |
| JP6966442B2 (ja) * | 2015-12-04 | 2021-11-17 | ソルボンヌ・ユニヴェルシテSorbonne Universite | プロモーター及びその使用 |
| US20190269755A1 (en) * | 2016-04-29 | 2019-09-05 | Gensight Biologics Sa | Optogenetic visual restoration using chrimson |
| PL239642B1 (pl) * | 2018-08-16 | 2021-12-20 | Pomorski Univ Medyczny W Szczecinie | Kompozycja do doszklistkowego podawania białka leczniczego |
| IL302164A (en) | 2020-10-22 | 2023-06-01 | Visgenx Inc | Elovl2 constructs for human gene therapy |
| JP2025540499A (ja) * | 2022-12-05 | 2025-12-11 | ザ ユナイテッド ステイツ オブ アメリカ， アズ リプレゼンテッド バイ ザ セクレタリー， デパートメント オブ ヘルス アンド ヒューマン サービシーズ | 色素上皮由来因子ペプチドおよび網膜変性症を処置するための使用 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5932479A (en) | 1988-09-26 | 1999-08-03 | Auburn University | Genetic engineering of plant chloroplasts |
| CA2293492A1 (en) * | 1997-06-11 | 1998-12-17 | Martin Berry | Cns neuroregenerative compositions and methods of use |
| CA2358296A1 (en) * | 1999-01-05 | 2000-07-13 | Anthony P. Adamis | Targeted transscleral controlled release drug delivery to the retina and choroid |
| AU3755900A (en) * | 1999-03-15 | 2000-10-04 | Chiron Corporation | Use of recombinant gene delivery vectors for treating or preventing diseases of the eye |
| US6943153B1 (en) * | 1999-03-15 | 2005-09-13 | The Regents Of The University Of California | Use of recombinant gene delivery vectors for treating or preventing diseases of the eye |
| EP1263934A4 (en) | 2000-02-29 | 2004-05-06 | Univ Auburn | GENETIC ENGINEERING OF DROUGHT TOLERANCE USING A PLASTIC GENOME |
| EP2080803B1 (en) | 2000-03-01 | 2011-05-25 | Auburn University | Plastid transformation vectors for expressing proinsulin fused to the cholera toxin B-subunit in plants |
| US7354760B2 (en) | 2001-12-26 | 2008-04-08 | University Of Central Florida Research Foundation, Inc. | Expression of protective antigens in transgenic chloroplasts |
| AU2003253781A1 (en) | 2002-07-03 | 2004-01-23 | University Of Central Florida | Expression of human interferon in transgenic chloroplasts |
| WO2006101634A1 (en) * | 2005-02-17 | 2006-09-28 | The Regents Of The University Of California | Müller cell specific gene therapy |
| US20060188481A1 (en) * | 2005-02-22 | 2006-08-24 | Saitama Medical School | Methods for prophylactically or therapeutically treating an animal for an ocular-related disorder |
| US7931891B2 (en) * | 2005-02-24 | 2011-04-26 | The Scripps Research Institute | Isolated myeloid-like bone marrow cell populations and methods of treatment therewith |
| US20080274143A1 (en) | 2005-05-27 | 2008-11-06 | Henry Daniell | Chloroplasts Engineering to Express Pharmaceutical Proteins |
| AU2009212309B2 (en) * | 2008-02-07 | 2014-04-03 | Ceregene, Inc. | Rescue of photoreceptors by intravitreal administration of an expression vector encoding a therapeutic protein |
-
2009
- 2009-02-05 AU AU2009212309A patent/AU2009212309B2/en not_active Ceased
- 2009-02-05 JP JP2010546007A patent/JP2011511090A/ja not_active Ceased
- 2009-02-05 EP EP09707354A patent/EP2247258A4/en not_active Withdrawn
- 2009-02-05 CA CA2713755A patent/CA2713755A1/en not_active Abandoned
- 2009-02-05 WO PCT/US2009/033275 patent/WO2009100253A1/en not_active Ceased
- 2009-02-05 CN CN2009801043603A patent/CN101980668A/zh active Pending
- 2009-02-05 US US12/366,596 patent/US8242093B2/en not_active Expired - Fee Related
-
2011
- 2011-08-17 US US13/212,078 patent/US8420619B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009100253A8 (en) | 2010-08-19 |
| AU2009212309B2 (en) | 2014-04-03 |
| US8242093B2 (en) | 2012-08-14 |
| EP2247258A1 (en) | 2010-11-10 |
| US20090202505A1 (en) | 2009-08-13 |
| CN101980668A (zh) | 2011-02-23 |
| WO2009100253A1 (en) | 2009-08-13 |
| AU2009212309A1 (en) | 2009-08-13 |
| US20120316112A1 (en) | 2012-12-13 |
| EP2247258A4 (en) | 2012-01-18 |
| US8420619B2 (en) | 2013-04-16 |
| JP2011511090A (ja) | 2011-04-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2009212309B2 (en) | Rescue of photoreceptors by intravitreal administration of an expression vector encoding a therapeutic protein | |
| Lau et al. | Retinal degeneration is slowed in transgenic rats by AAV-mediated delivery of FGF-2 | |
| Fuller-Carter et al. | Focused update on AAV-based gene therapy clinical trials for inherited retinal degeneration | |
| JP2019503664A (ja) | プロモーター及びその使用 | |
| US20230233709A1 (en) | Gene therapy for ocular disorders | |
| US20250059563A1 (en) | Constructs comprising neuronal viability factors and uses thereof | |
| JP7287611B2 (ja) | 改良型アデノ随伴ウイルスベクター | |
| Pang et al. | AAV-mediated gene therapy in mouse models of recessive retinal degeneration | |
| JP2024105661A (ja) | 眼疾患に対するａｄｅｎｏ随伴ウイルス連ウイルスベクター媒介遺伝子治療 | |
| Colella et al. | AAV-mediated gene supply for treatment of degenerative and neovascular retinal diseases | |
| Chekuri et al. | AAV2-mediated intravitreal delivery of exon-specific U1 snRNA rescues optic neuropathy in a mouse model of familial dysautonomia | |
| SK95599A3 (en) | Adenoviral-vector-mediated gene transfer into medullary motor neurons | |
| US20220143217A1 (en) | Neuroprotective gene therapy targeting the akt pathway | |
| WO2020163250A1 (en) | Cx3cl1 compositions and methods for the treatment of degenerative ocular diseases | |
| EP4326339B1 (en) | Compositions and methods for treating retinal degenerative disorders | |
| KR20250142239A (ko) | Egr1의 상향조절을 통한 안과 질환의 예방 또는 치료용 약학 조성물 | |
| JPWO2020154535A5 (OSRAM) | ||
| Parikh et al. | A path towards restoration of vision using ocular gene therapy: An ophthalmic review |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20140110 |
|
| FZDE | Dead |
Effective date: 20160205 |