AU2009212309B2 - 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
- AU2009212309B2 AU2009212309B2 AU2009212309A AU2009212309A AU2009212309B2 AU 2009212309 B2 AU2009212309 B2 AU 2009212309B2 AU 2009212309 A AU2009212309 A AU 2009212309A AU 2009212309 A AU2009212309 A AU 2009212309A AU 2009212309 B2 AU2009212309 B2 AU 2009212309B2
- Authority
- AU
- Australia
- Prior art keywords
- cells
- vector
- aav
- growth factor
- layer
- 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.)
- Ceased
Links
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 62
- 108091008695 photoreceptors Proteins 0.000 title claims abstract description 54
- 239000013604 expression vector Substances 0.000 title claims abstract description 37
- 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 132
- 210000001525 retina Anatomy 0.000 claims abstract description 80
- 239000013598 vector Substances 0.000 claims abstract description 52
- 239000003102 growth factor Substances 0.000 claims abstract description 48
- 238000000034 method Methods 0.000 claims abstract description 44
- 210000003994 retinal ganglion cell Anatomy 0.000 claims abstract description 41
- 208000022873 Ocular disease Diseases 0.000 claims abstract description 31
- 230000002207 retinal effect Effects 0.000 claims abstract description 27
- 238000011065 in-situ storage Methods 0.000 claims abstract description 17
- 238000003259 recombinant expression Methods 0.000 claims abstract description 14
- 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 40
- 239000007924 injection Substances 0.000 claims description 40
- 230000007850 degeneration Effects 0.000 claims description 32
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims description 26
- 230000004044 response Effects 0.000 claims description 19
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 claims description 16
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 claims description 16
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 claims description 16
- 208000002780 macular degeneration Diseases 0.000 claims description 16
- 239000013607 AAV vector Substances 0.000 claims description 14
- 210000001519 tissue Anatomy 0.000 claims description 13
- 210000000880 retinal rod photoreceptor cell Anatomy 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 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
- 238000002513 implantation Methods 0.000 claims description 9
- 210000005156 Müller Glia Anatomy 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 115
- 102000003683 Neurotrophin-4 Human genes 0.000 abstract description 113
- 229940097998 neurotrophin 4 Drugs 0.000 abstract description 108
- 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 72
- 108020004707 nucleic acids Proteins 0.000 description 47
- 102000039446 nucleic acids Human genes 0.000 description 47
- 239000010410 layer Substances 0.000 description 46
- 102000001839 Neurturin Human genes 0.000 description 28
- 108010015406 Neurturin Proteins 0.000 description 28
- 206010029113 Neovascularisation Diseases 0.000 description 20
- 108010025020 Nerve Growth Factor Proteins 0.000 description 18
- 241000700159 Rattus Species 0.000 description 18
- 239000012537 formulation buffer Substances 0.000 description 18
- 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
- 201000007737 Retinal degeneration Diseases 0.000 description 13
- 210000000608 photoreceptor cell Anatomy 0.000 description 13
- 102000007072 Nerve Growth Factors Human genes 0.000 description 12
- 230000004258 retinal degeneration Effects 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 11
- 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
- 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
- 208000015181 infectious disease Diseases 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
- 101150115477 Vldlr gene Proteins 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
- 102000015336 Nerve Growth Factor Human genes 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
- 229940053128 nerve growth factor Drugs 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
- 210000004498 neuroglial cell Anatomy 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
- 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
- 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
- 102100025248 C-X-C motif chemokine 10 Human genes 0.000 description 1
- -1 CM101 Chemical compound 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
- 101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 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
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 102000003810 Interleukin-18 Human genes 0.000 description 1
- 108090000171 Interleukin-18 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 102000004388 Interleukin-4 Human genes 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
- 230000000295 complement effect Effects 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
- 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)
- Neurosurgery (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Psychology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (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 (2)
| Publication Number | Publication Date |
|---|---|
| AU2009212309A1 AU2009212309A1 (en) | 2009-08-13 |
| AU2009212309B2 true AU2009212309B2 (en) | 2014-04-03 |
Family
ID=40939054
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2009212309A Ceased AU2009212309B2 (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 (enExample) |
| EP (1) | EP2247258A4 (enExample) |
| JP (1) | JP2011511090A (enExample) |
| CN (1) | CN101980668A (enExample) |
| AU (1) | AU2009212309B2 (enExample) |
| CA (1) | CA2713755A1 (enExample) |
| WO (1) | WO2009100253A1 (enExample) |
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 |
| CN103459593A (zh) * | 2011-02-25 | 2013-12-18 | 独立行政法人理化学研究所 | 视网膜色素上皮细胞片层的生产方法 |
| 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 |
| US20160256571A1 (en) * | 2013-09-30 | 2016-09-08 | Sanofi | Invention |
| WO2015082690A1 (en) * | 2013-12-06 | 2015-06-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for expressing a polynucleotide of interest in the retinal pigment epithelium of a subject |
| US10293059B2 (en) * | 2015-04-09 | 2019-05-21 | Cornell University | Gene therapy to prevent reactions to allergens |
| US11390866B2 (en) * | 2015-12-04 | 2022-07-19 | Sorbonne Université | Promoters and uses thereof |
| EP3448411A1 (en) * | 2016-04-29 | 2019-03-06 | 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 |
| CN116916937A (zh) * | 2020-10-22 | 2023-10-20 | 维斯基因股份有限公司 | 用于人类基因疗法的elovl2构建体 |
| WO2024123461A1 (en) * | 2022-12-05 | 2024-06-13 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Pigment epithelium-derived factor peptides and use for treating retinal degeneration |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020194630A1 (en) * | 1999-03-15 | 2002-12-19 | Manning William C. | Use of recombinant gene delivery vectors for treating or preventing diseases of the eye |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5932479A (en) | 1988-09-26 | 1999-08-03 | Auburn University | Genetic engineering of plant chloroplasts |
| WO1998056404A1 (en) * | 1997-06-11 | 1998-12-17 | Acorda Therapeutics | Cns neuroregenerative compositions and methods of use |
| JP2002534139A (ja) * | 1999-01-05 | 2002-10-15 | マサチューセッツ・アイ・アンド・イア・インファーマリー | 網膜と脈絡膜への経強膜徐放性薬剤標的送達 |
| CA2367375A1 (en) * | 1999-03-15 | 2000-09-21 | Chiron Corporation | Use of recombinant gene delivery vectors for treating or preventing diseases of the eye |
| CA2401855A1 (en) | 2000-02-29 | 2001-09-07 | Auburn University | Genetic engineering of drought tolerance via a plastid genome |
| CA2402066C (en) | 2000-03-01 | 2015-09-29 | Auburn University | Plastid transformation vectors for expressing human proteins 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 |
| US20100172871A1 (en) * | 2005-02-17 | 2010-07-08 | Flannery John G | Muller 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 |
| JP2008537478A (ja) * | 2005-02-24 | 2008-09-18 | ザ・スクリプス・リサーチ・インステイチユート | 単離骨髄球様骨髄細胞集団及びそれを用いた治療方法 |
| AU2006309281B2 (en) | 2005-05-27 | 2011-11-03 | University Of Central Florida | Chloroplasts engineered 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 US US12/366,596 patent/US8242093B2/en not_active Expired - Fee Related
- 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 CA CA2713755A patent/CA2713755A1/en not_active Abandoned
- 2009-02-05 EP EP09707354A patent/EP2247258A4/en not_active Withdrawn
- 2009-02-05 JP JP2010546007A patent/JP2011511090A/ja not_active Ceased
-
2011
- 2011-08-17 US US13/212,078 patent/US8420619B2/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020194630A1 (en) * | 1999-03-15 | 2002-12-19 | Manning William C. | Use of recombinant gene delivery vectors for treating or preventing diseases of the eye |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101980668A (zh) | 2011-02-23 |
| WO2009100253A8 (en) | 2010-08-19 |
| WO2009100253A1 (en) | 2009-08-13 |
| US8420619B2 (en) | 2013-04-16 |
| AU2009212309A1 (en) | 2009-08-13 |
| US8242093B2 (en) | 2012-08-14 |
| US20090202505A1 (en) | 2009-08-13 |
| EP2247258A1 (en) | 2010-11-10 |
| US20120316112A1 (en) | 2012-12-13 |
| CA2713755A1 (en) | 2009-08-13 |
| JP2011511090A (ja) | 2011-04-07 |
| EP2247258A4 (en) | 2012-01-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2009212309B2 (en) | Rescue of photoreceptors by intravitreal administration of an expression vector encoding a therapeutic protein | |
| US6204251B1 (en) | Ocular gene therapy | |
| 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 | |
| Chekuri et al. | AAV2-mediated intravitreal delivery of exon-specific U1 snRNA rescues optic neuropathy in a mouse model of familial dysautonomia | |
| 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 | |
| Chacón-Camacho et al. | Gene therapy for hereditary ophthalmological diseases: Advances and future perspectives | |
| JPWO2020154535A5 (enExample) | ||
| Parikh et al. | A path towards restoration of vision using ocular gene therapy: An ophthalmic review |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| DA3 | Amendments made section 104 |
Free format text: THE NATURE OF THE AMENDMENT IS: AMEND THE INVENTION TITLE TO READ RESCUE OF PHOTORECEPTORS BY INTRAVITREAL ADMINISTRATION OF AN EXPRESSION VECTOR ENCODING A THERAPEUTIC PROTEIN |
|
| FGA | Letters patent sealed or granted (standard patent) | ||
| MK14 | Patent ceased section 143(a) (annual fees not paid) or expired |