JP6689249B2 - 錐体細胞における増強された遺伝子発現のための組成物および方法 - Google Patents
錐体細胞における増強された遺伝子発現のための組成物および方法 Download PDFInfo
- Publication number
- JP6689249B2 JP6689249B2 JP2017501086A JP2017501086A JP6689249B2 JP 6689249 B2 JP6689249 B2 JP 6689249B2 JP 2017501086 A JP2017501086 A JP 2017501086A JP 2017501086 A JP2017501086 A JP 2017501086A JP 6689249 B2 JP6689249 B2 JP 6689249B2
- Authority
- JP
- Japan
- Prior art keywords
- seq
- sequence
- polynucleotide
- expression
- cells
- 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.)
- Active
Links
- 230000014509 gene expression Effects 0.000 title claims description 237
- 210000002763 pyramidal cell Anatomy 0.000 title claims description 133
- 239000000203 mixture Substances 0.000 title claims description 69
- 238000000034 method Methods 0.000 title description 110
- 102000040430 polynucleotide Human genes 0.000 claims description 232
- 108091033319 polynucleotide Proteins 0.000 claims description 232
- 239000002157 polynucleotide Substances 0.000 claims description 232
- 108090000623 proteins and genes Proteins 0.000 claims description 161
- 239000002773 nucleotide Substances 0.000 claims description 121
- 125000003729 nucleotide group Chemical group 0.000 claims description 121
- 108700019146 Transgenes Proteins 0.000 claims description 112
- 108091026890 Coding region Proteins 0.000 claims description 86
- 108700039691 Genetic Promoter Regions Proteins 0.000 claims description 81
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 76
- 230000004456 color vision Effects 0.000 claims description 68
- 210000001525 retina Anatomy 0.000 claims description 68
- 108020003589 5' Untranslated Regions Proteins 0.000 claims description 63
- 208000002780 macular degeneration Diseases 0.000 claims description 43
- 208000035475 disorder Diseases 0.000 claims description 42
- 210000000964 retinal cone photoreceptor cell Anatomy 0.000 claims description 42
- 108700026244 Open Reading Frames Proteins 0.000 claims description 40
- 239000012634 fragment Substances 0.000 claims description 35
- 241000124008 Mammalia Species 0.000 claims description 31
- 230000001225 therapeutic effect Effects 0.000 claims description 31
- 108700028146 Genetic Enhancer Elements Proteins 0.000 claims description 27
- 208000035719 Maculopathy Diseases 0.000 claims description 24
- 230000004393 visual impairment Effects 0.000 claims description 24
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 23
- 102000010175 Opsin Human genes 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 230000008488 polyadenylation Effects 0.000 claims description 23
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims description 22
- 230000014621 translational initiation Effects 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 20
- 206010025421 Macule Diseases 0.000 claims description 17
- 108090000565 Capsid Proteins Proteins 0.000 claims description 15
- 102100023321 Ceruloplasmin Human genes 0.000 claims description 15
- 241000702421 Dependoparvovirus Species 0.000 claims description 15
- 208000010412 Glaucoma Diseases 0.000 claims description 14
- 201000006754 cone-rod dystrophy Diseases 0.000 claims description 14
- 201000003533 Leber congenital amaurosis Diseases 0.000 claims description 12
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 12
- 108700009124 Transcription Initiation Site Proteins 0.000 claims description 11
- 208000029257 vision disease Diseases 0.000 claims description 11
- 108091026898 Leader sequence (mRNA) Proteins 0.000 claims description 10
- 206010043189 Telangiectasia Diseases 0.000 claims description 10
- 208000009056 telangiectasis Diseases 0.000 claims description 10
- 230000007850 degeneration Effects 0.000 claims description 9
- 208000004644 retinal vein occlusion Diseases 0.000 claims description 9
- 102220467647 Long-wave-sensitive opsin 1_I274V_mutation Human genes 0.000 claims description 7
- 102220344502 c.853A>G Human genes 0.000 claims description 7
- 201000007790 vitelliform macular dystrophy Diseases 0.000 claims description 7
- 102220474405 Long-wave-sensitive opsin 1_I111V_mutation Human genes 0.000 claims description 6
- 102220467749 Long-wave-sensitive opsin 1_S116Y_mutation Human genes 0.000 claims description 6
- 206010025412 Macular dystrophy congenital Diseases 0.000 claims description 6
- 102220512669 Olfactory receptor 51A7_Y277F_mutation Human genes 0.000 claims description 6
- 201000001408 X-linked juvenile retinoschisis 1 Diseases 0.000 claims description 6
- 208000017441 X-linked retinoschisis Diseases 0.000 claims description 6
- 201000007714 retinoschisis Diseases 0.000 claims description 6
- 102220212468 rs145009674 Human genes 0.000 claims description 6
- 102220187193 rs145041032 Human genes 0.000 claims description 6
- 102220050340 rs193920890 Human genes 0.000 claims description 6
- 102220044497 rs587781345 Human genes 0.000 claims description 6
- 102220085731 rs771364038 Human genes 0.000 claims description 6
- 102200056668 rs76863441 Human genes 0.000 claims description 5
- 208000036693 Color-vision disease Diseases 0.000 claims description 4
- 102220467646 Long-wave-sensitive opsin 1_I230T_mutation Human genes 0.000 claims description 4
- 206010047571 Visual impairment Diseases 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 101150004094 PRO2 gene Proteins 0.000 claims 3
- 102100021244 Integral membrane protein GPR180 Human genes 0.000 claims 1
- 102220030661 rs367601527 Human genes 0.000 claims 1
- 102200117832 rs61754966 Human genes 0.000 claims 1
- 102220057163 rs730880848 Human genes 0.000 claims 1
- 210000004027 cell Anatomy 0.000 description 150
- 239000013598 vector Substances 0.000 description 149
- 210000001508 eye Anatomy 0.000 description 69
- 238000012360 testing method Methods 0.000 description 51
- 108090000765 processed proteins & peptides Proteins 0.000 description 45
- 238000011144 upstream manufacturing Methods 0.000 description 45
- 229920001184 polypeptide Polymers 0.000 description 40
- 102000004196 processed proteins & peptides Human genes 0.000 description 40
- 241001465754 Metazoa Species 0.000 description 36
- 241000288906 Primates Species 0.000 description 36
- 239000000047 product Substances 0.000 description 36
- 241000700605 Viruses Species 0.000 description 35
- 201000010099 disease Diseases 0.000 description 34
- 230000000694 effects Effects 0.000 description 34
- 230000004438 eyesight Effects 0.000 description 33
- 238000001476 gene delivery Methods 0.000 description 33
- 239000007924 injection Substances 0.000 description 30
- 238000002347 injection Methods 0.000 description 30
- 241000699694 Gerbillinae Species 0.000 description 29
- 230000035772 mutation Effects 0.000 description 28
- 102000004169 proteins and genes Human genes 0.000 description 28
- 230000002207 retinal effect Effects 0.000 description 28
- 239000003623 enhancer Substances 0.000 description 27
- 235000018102 proteins Nutrition 0.000 description 27
- 230000001976 improved effect Effects 0.000 description 25
- 235000002639 sodium chloride Nutrition 0.000 description 25
- 208000024891 symptom Diseases 0.000 description 25
- 108020004705 Codon Proteins 0.000 description 24
- 238000001727 in vivo Methods 0.000 description 24
- 101000598988 Mus musculus Medium-wave-sensitive opsin 1 Proteins 0.000 description 23
- 108050001704 Opsin Proteins 0.000 description 22
- 239000002245 particle Substances 0.000 description 22
- 241000282414 Homo sapiens Species 0.000 description 21
- 230000001965 increasing effect Effects 0.000 description 20
- 201000004569 Blindness Diseases 0.000 description 19
- 230000006870 function Effects 0.000 description 19
- 210000001519 tissue Anatomy 0.000 description 19
- 238000001415 gene therapy Methods 0.000 description 18
- 238000012014 optical coherence tomography Methods 0.000 description 18
- 208000011580 syndromic disease Diseases 0.000 description 18
- 208000006992 Color Vision Defects Diseases 0.000 description 17
- 201000007254 color blindness Diseases 0.000 description 17
- 150000007523 nucleic acids Chemical class 0.000 description 17
- 230000001105 regulatory effect Effects 0.000 description 17
- 150000003839 salts Chemical class 0.000 description 17
- 230000003612 virological effect Effects 0.000 description 17
- 235000001014 amino acid Nutrition 0.000 description 16
- 238000003384 imaging method Methods 0.000 description 16
- 108091092195 Intron Proteins 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 15
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 15
- 239000003814 drug Substances 0.000 description 15
- 102000039446 nucleic acids Human genes 0.000 description 15
- 108020004707 nucleic acids Proteins 0.000 description 15
- 239000002953 phosphate buffered saline Substances 0.000 description 15
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 14
- 108020004414 DNA Proteins 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 150000001413 amino acids Chemical class 0.000 description 14
- 230000004304 visual acuity Effects 0.000 description 14
- 230000000007 visual effect Effects 0.000 description 14
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 13
- 239000013607 AAV vector Substances 0.000 description 13
- 230000035945 sensitivity Effects 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 108091028043 Nucleic acid sequence Proteins 0.000 description 12
- 230000000295 complement effect Effects 0.000 description 12
- 238000000338 in vitro Methods 0.000 description 12
- 239000013612 plasmid Substances 0.000 description 12
- 239000013608 rAAV vector Substances 0.000 description 12
- 229940124597 therapeutic agent Drugs 0.000 description 12
- 230000014616 translation Effects 0.000 description 12
- 238000013519 translation Methods 0.000 description 12
- 210000002845 virion Anatomy 0.000 description 12
- 108060001084 Luciferase Proteins 0.000 description 11
- 239000005089 Luciferase Substances 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 11
- 125000003275 alpha amino acid group Chemical group 0.000 description 11
- 230000000875 corresponding effect Effects 0.000 description 11
- 108020004999 messenger RNA Proteins 0.000 description 11
- 208000034461 Progressive cone dystrophy Diseases 0.000 description 10
- 241000700159 Rattus Species 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 210000000234 capsid Anatomy 0.000 description 10
- 201000008615 cone dystrophy Diseases 0.000 description 10
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 10
- 239000011780 sodium chloride Substances 0.000 description 10
- 208000017442 Retinal disease Diseases 0.000 description 9
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 230000004064 dysfunction Effects 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
- 241000894007 species Species 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- 241000282552 Chlorocebus aethiops Species 0.000 description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 101000919370 Homo sapiens Cone-rod homeobox protein Proteins 0.000 description 8
- 108091023045 Untranslated Region Proteins 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 230000006378 damage Effects 0.000 description 8
- 239000013604 expression vector Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 238000005457 optimization Methods 0.000 description 8
- 239000013646 rAAV2 vector Substances 0.000 description 8
- 201000003632 spinocerebellar ataxia type 7 Diseases 0.000 description 8
- 238000013518 transcription Methods 0.000 description 8
- 230000035897 transcription Effects 0.000 description 8
- 238000010361 transduction Methods 0.000 description 8
- 230000026683 transduction Effects 0.000 description 8
- 206010003694 Atrophy Diseases 0.000 description 7
- 108091006146 Channels Proteins 0.000 description 7
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 7
- 102100039214 Guanine nucleotide-binding protein G(t) subunit alpha-2 Human genes 0.000 description 7
- 101000888142 Homo sapiens Guanine nucleotide-binding protein G(t) subunit alpha-2 Proteins 0.000 description 7
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 7
- 208000001140 Night Blindness Diseases 0.000 description 7
- 229930040373 Paraformaldehyde Natural products 0.000 description 7
- 230000037444 atrophy Effects 0.000 description 7
- 230000003915 cell function Effects 0.000 description 7
- 230000003833 cell viability Effects 0.000 description 7
- 230000007547 defect Effects 0.000 description 7
- 201000011190 diabetic macular edema Diseases 0.000 description 7
- 238000010586 diagram Methods 0.000 description 7
- 239000012530 fluid Substances 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 229960003299 ketamine Drugs 0.000 description 7
- 208000018769 loss of vision Diseases 0.000 description 7
- 231100000864 loss of vision Toxicity 0.000 description 7
- 229920002866 paraformaldehyde Polymers 0.000 description 7
- 230000002093 peripheral effect Effects 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- 108091008695 photoreceptors Proteins 0.000 description 7
- 230000000750 progressive effect Effects 0.000 description 7
- 239000004055 small Interfering RNA Substances 0.000 description 7
- 230000035899 viability Effects 0.000 description 7
- 241000283690 Bos taurus Species 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 101710137010 Retinol-binding protein 3 Proteins 0.000 description 6
- 102100038247 Retinol-binding protein 3 Human genes 0.000 description 6
- 206010038923 Retinopathy Diseases 0.000 description 6
- 102100040092 X-linked retinitis pigmentosa GTPase regulator Human genes 0.000 description 6
- 239000003937 drug carrier Substances 0.000 description 6
- 238000000799 fluorescence microscopy Methods 0.000 description 6
- 230000002068 genetic effect Effects 0.000 description 6
- 238000003780 insertion Methods 0.000 description 6
- 230000037431 insertion Effects 0.000 description 6
- -1 minicircle Substances 0.000 description 6
- 239000000049 pigment Substances 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 239000013603 viral vector Substances 0.000 description 6
- 238000012800 visualization Methods 0.000 description 6
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 6
- 229960001600 xylazine Drugs 0.000 description 6
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 5
- 102100029362 Cone-rod homeobox protein Human genes 0.000 description 5
- 102220536738 Hemoglobin subunit epsilon_A174V_mutation Human genes 0.000 description 5
- 241000282412 Homo Species 0.000 description 5
- 101001104102 Homo sapiens X-linked retinitis pigmentosa GTPase regulator Proteins 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 206010034960 Photophobia Diseases 0.000 description 5
- 108010076504 Protein Sorting Signals Proteins 0.000 description 5
- 108050009315 Retinitis pigmentosa GTPase regulator-interacting protein 1 Proteins 0.000 description 5
- 102000002017 Retinitis pigmentosa GTPase regulator-interacting protein 1 Human genes 0.000 description 5
- 208000027073 Stargardt disease Diseases 0.000 description 5
- 230000003044 adaptive effect Effects 0.000 description 5
- 125000000539 amino acid group Chemical group 0.000 description 5
- 201000007917 background diabetic retinopathy Diseases 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
- 230000003292 diminished effect Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 238000004806 packaging method and process Methods 0.000 description 5
- 230000008447 perception Effects 0.000 description 5
- 230000001737 promoting effect Effects 0.000 description 5
- 102220236764 rs777515082 Human genes 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 4
- 241000202702 Adeno-associated virus - 3 Species 0.000 description 4
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 4
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 4
- 241001164823 Adeno-associated virus - 7 Species 0.000 description 4
- 241001164825 Adeno-associated virus - 8 Species 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 241000283707 Capra Species 0.000 description 4
- 241000282692 Catarrhini Species 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 101001044118 Homo sapiens Inosine-5'-monophosphate dehydrogenase 1 Proteins 0.000 description 4
- 101001008411 Homo sapiens Lebercilin Proteins 0.000 description 4
- 101000899806 Homo sapiens Retinal guanylyl cyclase 1 Proteins 0.000 description 4
- 102100021602 Inosine-5'-monophosphate dehydrogenase 1 Human genes 0.000 description 4
- 201000009710 Leber congenital amaurosis 5 Diseases 0.000 description 4
- 102100027443 Lebercilin Human genes 0.000 description 4
- 241001494479 Pecora Species 0.000 description 4
- 206010038848 Retinal detachment Diseases 0.000 description 4
- 102100022663 Retinal guanylyl cyclase 1 Human genes 0.000 description 4
- 102100038054 Retinol dehydrogenase 12 Human genes 0.000 description 4
- 108091027967 Small hairpin RNA Proteins 0.000 description 4
- 108020004566 Transfer RNA Proteins 0.000 description 4
- 230000005856 abnormality Effects 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 4
- 201000000761 achromatopsia Diseases 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 230000004075 alteration Effects 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 210000004204 blood vessel Anatomy 0.000 description 4
- 238000002659 cell therapy Methods 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000000975 dye Substances 0.000 description 4
- 208000030533 eye disease Diseases 0.000 description 4
- 238000013534 fluorescein angiography Methods 0.000 description 4
- 230000001771 impaired effect Effects 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 230000000977 initiatory effect Effects 0.000 description 4
- 210000004962 mammalian cell Anatomy 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000011159 matrix material Substances 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- 206010029864 nystagmus Diseases 0.000 description 4
- 210000001328 optic nerve Anatomy 0.000 description 4
- 230000005043 peripheral vision Effects 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 239000013641 positive control Substances 0.000 description 4
- 201000007914 proliferative diabetic retinopathy Diseases 0.000 description 4
- 102220320105 rs772037564 Human genes 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 208000036443 AIPL1-related retinopathy Diseases 0.000 description 3
- 102100024081 Aryl-hydrocarbon-interacting protein-like 1 Human genes 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 3
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 3
- 102100039484 Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' Human genes 0.000 description 3
- 108091035707 Consensus sequence Proteins 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000282326 Felis catus Species 0.000 description 3
- 102100033969 Guanylyl cyclase-activating protein 1 Human genes 0.000 description 3
- 108050003684 Guanylyl cyclase-activating protein 1 Proteins 0.000 description 3
- 101000833576 Homo sapiens Aryl-hydrocarbon-interacting protein-like 1 Proteins 0.000 description 3
- 101000742938 Homo sapiens Retinol dehydrogenase 12 Proteins 0.000 description 3
- 241000713666 Lentivirus Species 0.000 description 3
- 208000010415 Low Vision Diseases 0.000 description 3
- 101710131036 Opsin-1 Proteins 0.000 description 3
- 241000282520 Papio Species 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 241000283984 Rodentia Species 0.000 description 3
- 101710106192 Short-wave-sensitive opsin 1 Proteins 0.000 description 3
- 108020004459 Small interfering RNA Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 3
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
- 206010047513 Vision blurred Diseases 0.000 description 3
- 208000013521 Visual disease Diseases 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 3
- 230000000975 bioactive effect Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 238000005415 bioluminescence Methods 0.000 description 3
- 230000029918 bioluminescence Effects 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 238000002571 electroretinography Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 208000017532 inherited retinal dystrophy Diseases 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000000366 juvenile effect Effects 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 238000004020 luminiscence type Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000004297 night vision Effects 0.000 description 3
- 229940124531 pharmaceutical excipient Drugs 0.000 description 3
- 210000000608 photoreceptor cell Anatomy 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 210000001747 pupil Anatomy 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 230000004264 retinal detachment Effects 0.000 description 3
- 210000000880 retinal rod photoreceptor cell Anatomy 0.000 description 3
- 102220317277 rs1318754770 Human genes 0.000 description 3
- 230000004434 saccadic eye movement Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 230000003595 spectral effect Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 150000008163 sugars Chemical class 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000002463 transducing effect Effects 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 241000701161 unidentified adenovirus Species 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 241000649045 Adeno-associated virus 10 Species 0.000 description 2
- 206010003591 Ataxia Diseases 0.000 description 2
- 108010032953 Ataxin-7 Proteins 0.000 description 2
- 108091005462 Cation channels Proteins 0.000 description 2
- 206010008025 Cerebellar ataxia Diseases 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 108010003730 Cone Opsins Proteins 0.000 description 2
- 102100029140 Cyclic nucleotide-gated cation channel beta-3 Human genes 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- IGXWBGJHJZYPQS-SSDOTTSWSA-N D-Luciferin Chemical compound OC(=O)[C@H]1CSC(C=2SC3=CC=C(O)C=C3N=2)=N1 IGXWBGJHJZYPQS-SSDOTTSWSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
- CYCGRDQQIOGCKX-UHFFFAOYSA-N Dehydro-luciferin Natural products OC(=O)C1=CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 CYCGRDQQIOGCKX-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241000283074 Equus asinus Species 0.000 description 2
- 241000283073 Equus caballus Species 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 241000714165 Feline leukemia virus Species 0.000 description 2
- BJGNCJDXODQBOB-UHFFFAOYSA-N Fivefly Luciferin Natural products OC(=O)C1CSC(C=2SC3=CC(O)=CC=C3N=2)=N1 BJGNCJDXODQBOB-UHFFFAOYSA-N 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 241001272567 Hominoidea Species 0.000 description 2
- 101000697700 Homo sapiens Bardet-Biedl syndrome 2 protein Proteins 0.000 description 2
- 101000609790 Homo sapiens Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' Proteins 0.000 description 2
- 101000771083 Homo sapiens Cyclic nucleotide-gated cation channel beta-3 Proteins 0.000 description 2
- 101000899111 Homo sapiens Hemoglobin subunit beta Proteins 0.000 description 2
- 101000996052 Homo sapiens Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1 Proteins 0.000 description 2
- 101000610652 Homo sapiens Peripherin-2 Proteins 0.000 description 2
- 101000610551 Homo sapiens Prominin-1 Proteins 0.000 description 2
- 101000726148 Homo sapiens Protein crumbs homolog 1 Proteins 0.000 description 2
- 101000801643 Homo sapiens Retinal-specific phospholipid-transporting ATPase ABCA4 Proteins 0.000 description 2
- 101000729271 Homo sapiens Retinoid isomerohydrolase Proteins 0.000 description 2
- 101001010792 Homo sapiens Transcriptional regulator ERG Proteins 0.000 description 2
- 108091006905 Human Serum Albumin Proteins 0.000 description 2
- 102000008100 Human Serum Albumin Human genes 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 208000032578 Inherited retinal disease Diseases 0.000 description 2
- 102100033356 Lecithin retinol acyltransferase Human genes 0.000 description 2
- DDWFXDSYGUXRAY-UHFFFAOYSA-N Luciferin Natural products CCc1c(C)c(CC2NC(=O)C(=C2C=C)C)[nH]c1Cc3[nH]c4C(=C5/NC(CC(=O)O)C(C)C5CC(=O)O)CC(=O)c4c3C DDWFXDSYGUXRAY-UHFFFAOYSA-N 0.000 description 2
- 102000043136 MAP kinase family Human genes 0.000 description 2
- 108091054455 MAP kinase family Proteins 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241000713869 Moloney murine leukemia virus Species 0.000 description 2
- 241000713862 Moloney murine sarcoma virus Species 0.000 description 2
- 241000713333 Mouse mammary tumor virus Species 0.000 description 2
- 208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 description 2
- 102100034451 Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1 Human genes 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- 206010030348 Open-Angle Glaucoma Diseases 0.000 description 2
- 102100035714 Oxygen-regulated protein 1 Human genes 0.000 description 2
- 101710150924 Oxygen-regulated protein 1 Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 102100040375 Peripherin-2 Human genes 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 102100035846 Pigment epithelium-derived factor Human genes 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 102100022807 Potassium voltage-gated channel subfamily H member 2 Human genes 0.000 description 2
- 102100040120 Prominin-1 Human genes 0.000 description 2
- 102100027331 Protein crumbs homolog 1 Human genes 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 102100033844 Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma Human genes 0.000 description 2
- 208000032430 Retinal dystrophy Diseases 0.000 description 2
- 102100033617 Retinal-specific phospholipid-transporting ATPase ABCA4 Human genes 0.000 description 2
- 102100031176 Retinoid isomerohydrolase Human genes 0.000 description 2
- 241000714474 Rous sarcoma virus Species 0.000 description 2
- 206010039729 Scotoma Diseases 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 108010087042 Transducin Proteins 0.000 description 2
- 102000006612 Transducin Human genes 0.000 description 2
- 208000000208 Wet Macular Degeneration Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004155 blood-retinal barrier Anatomy 0.000 description 2
- 230000004378 blood-retinal barrier Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000005779 cell damage Effects 0.000 description 2
- 208000037887 cell injury Diseases 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 208000006394 cone dystrophy 4 Diseases 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 208000011325 dry age related macular degeneration Diseases 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000004424 eye movement Effects 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 201000006321 fundus dystrophy Diseases 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 238000010353 genetic engineering Methods 0.000 description 2
- 208000035474 group of disease Diseases 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 230000004410 intraocular pressure Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 229920002521 macromolecule Polymers 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 108091070501 miRNA Proteins 0.000 description 2
- 239000002679 microRNA Substances 0.000 description 2
- 238000000520 microinjection Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 2
- 229960001802 phenylephrine Drugs 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 230000000649 photocoagulation Effects 0.000 description 2
- 108090000102 pigment epithelium-derived factor Proteins 0.000 description 2
- 102000054765 polymorphisms of proteins Human genes 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000004439 pupillary reactions Effects 0.000 description 2
- 230000008085 renal dysfunction Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 102220323537 rs1555165268 Human genes 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 210000003786 sclera Anatomy 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 230000002123 temporal effect Effects 0.000 description 2
- 230000008719 thickening Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 description 1
- 101150084750 1 gene Proteins 0.000 description 1
- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- BFUUJUGQJUTPAF-UHFFFAOYSA-N 2-(3-amino-4-propoxybenzoyl)oxyethyl-diethylazanium;chloride Chemical compound [Cl-].CCCOC1=CC=C(C(=O)OCC[NH+](CC)CC)C=C1N BFUUJUGQJUTPAF-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical class CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000035502 ADME Effects 0.000 description 1
- OIRDTQYFTABQOQ-KQYNXXCUSA-N Adenosine Natural products C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000024985 Alport syndrome Diseases 0.000 description 1
- 208000031277 Amaurotic familial idiocy Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 102000009840 Angiopoietins Human genes 0.000 description 1
- 108010009906 Angiopoietins Proteins 0.000 description 1
- 201000002862 Angle-Closure Glaucoma Diseases 0.000 description 1
- 108020005098 Anticodon Proteins 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 101100437118 Arabidopsis thaliana AUG1 gene Proteins 0.000 description 1
- 101100437119 Arabidopsis thaliana AUG2 gene Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 102000003916 Arrestin Human genes 0.000 description 1
- 108090000328 Arrestin Proteins 0.000 description 1
- 108050003620 Arrestin-C Proteins 0.000 description 1
- 102100026440 Arrestin-C Human genes 0.000 description 1
- BHELIUBJHYAEDK-OAIUPTLZSA-N Aspoxicillin Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3[C@H](C(C)(C)S[C@@H]32)C(O)=O)=O)NC(=O)[C@H](N)CC(=O)NC)=CC=C(O)C=C1 BHELIUBJHYAEDK-OAIUPTLZSA-N 0.000 description 1
- 102000007368 Ataxin-7 Human genes 0.000 description 1
- 108010078286 Ataxins Proteins 0.000 description 1
- 102000014461 Ataxins Human genes 0.000 description 1
- 206010003671 Atrioventricular Block Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 208000000412 Avitaminosis Diseases 0.000 description 1
- 101150077415 BEST1 gene Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108700003860 Bacterial Genes Proteins 0.000 description 1
- 208000037663 Best vitelliform macular dystrophy Diseases 0.000 description 1
- 102100022794 Bestrophin-1 Human genes 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 102100022002 CD59 glycoprotein Human genes 0.000 description 1
- 208000035545 CNGA3-related retinopathy Diseases 0.000 description 1
- 102100035344 Cadherin-related family member 1 Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 101150044789 Cap gene Proteins 0.000 description 1
- 101710112958 Carbonyl reductase [NADPH] 2 Proteins 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 102100029855 Caspase-3 Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 206010007747 Cataract congenital Diseases 0.000 description 1
- 108010035848 Channelrhodopsins Proteins 0.000 description 1
- 101710163595 Chaperone protein DnaK Proteins 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 108091062157 Cis-regulatory element Proteins 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 101710204268 Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' Proteins 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 102100029141 Cyclic nucleotide-gated cation channel beta-1 Human genes 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 208000018672 Dilatation Diseases 0.000 description 1
- 208000003164 Diplopia Diseases 0.000 description 1
- 102100024361 Disintegrin and metalloproteinase domain-containing protein 9 Human genes 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 206010070917 Eccentric fixation Diseases 0.000 description 1
- 102100032053 Elongation of very long chain fatty acids protein 4 Human genes 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 206010015958 Eye pain Diseases 0.000 description 1
- 206010015995 Eyelid ptosis Diseases 0.000 description 1
- 206010016807 Fluid retention Diseases 0.000 description 1
- 241000714188 Friend murine leukemia virus Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 101150066002 GFP gene Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 208000008069 Geographic Atrophy Diseases 0.000 description 1
- 241000282575 Gorilla Species 0.000 description 1
- 102100039261 Guanine nucleotide-binding protein G(t) subunit alpha-1 Human genes 0.000 description 1
- 108010078321 Guanylate Cyclase Proteins 0.000 description 1
- 102000014469 Guanylate cyclase Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 108010050754 Halorhodopsins Proteins 0.000 description 1
- 241000713858 Harvey murine sarcoma virus Species 0.000 description 1
- 208000010271 Heart Block Diseases 0.000 description 1
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 1
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 1
- 102100021519 Hemoglobin subunit beta Human genes 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical group 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
- 208000028782 Hereditary disease Diseases 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000594506 Homo sapiens Acyl-coenzyme A diphosphatase NUDT19 Proteins 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101000903449 Homo sapiens Bestrophin-1 Proteins 0.000 description 1
- 101000897400 Homo sapiens CD59 glycoprotein Proteins 0.000 description 1
- 101000737767 Homo sapiens Cadherin-related family member 1 Proteins 0.000 description 1
- 101000771075 Homo sapiens Cyclic nucleotide-gated cation channel beta-1 Proteins 0.000 description 1
- 101000832769 Homo sapiens Disintegrin and metalloproteinase domain-containing protein 9 Proteins 0.000 description 1
- 101000921354 Homo sapiens Elongation of very long chain fatty acids protein 4 Proteins 0.000 description 1
- 101000888178 Homo sapiens Guanine nucleotide-binding protein G(t) subunit alpha-1 Proteins 0.000 description 1
- 101001011412 Homo sapiens IQ calmodulin-binding motif-containing protein 1 Proteins 0.000 description 1
- 101000998969 Homo sapiens Inositol-3-phosphate synthase 1 Proteins 0.000 description 1
- 101001047038 Homo sapiens Inward rectifier potassium channel 13 Proteins 0.000 description 1
- 101001017786 Homo sapiens Lecithin retinol acyltransferase Proteins 0.000 description 1
- 101000598981 Homo sapiens Medium-wave-sensitive opsin 2 Proteins 0.000 description 1
- 101000583150 Homo sapiens Membrane-associated phosphatidylinositol transfer protein 3 Proteins 0.000 description 1
- 101001105683 Homo sapiens Pre-mRNA-processing-splicing factor 8 Proteins 0.000 description 1
- 101000781361 Homo sapiens Protein XRP2 Proteins 0.000 description 1
- 101001074528 Homo sapiens Regulating synaptic membrane exocytosis protein 1 Proteins 0.000 description 1
- 101001132674 Homo sapiens Retina and anterior neural fold homeobox protein 2 Proteins 0.000 description 1
- 101000710852 Homo sapiens Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma Proteins 0.000 description 1
- 101001078886 Homo sapiens Retinaldehyde-binding protein 1 Proteins 0.000 description 1
- 101000611338 Homo sapiens Rhodopsin Proteins 0.000 description 1
- 101000609947 Homo sapiens Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha Proteins 0.000 description 1
- 101000609949 Homo sapiens Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta Proteins 0.000 description 1
- 101000652369 Homo sapiens Spermatogenesis-associated protein 7 Proteins 0.000 description 1
- 101000772173 Homo sapiens Tubby-related protein 1 Proteins 0.000 description 1
- 101000805941 Homo sapiens Usherin Proteins 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 239000000854 Human Growth Hormone Substances 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 208000015178 Hurler syndrome Diseases 0.000 description 1
- 241000282596 Hylobatidae Species 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020675 Hypermetropia Diseases 0.000 description 1
- 208000003623 Hypoalbuminemia Diseases 0.000 description 1
- 206010021135 Hypovitaminosis Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 102100029842 IQ calmodulin-binding motif-containing protein 1 Human genes 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 102100036881 Inositol-3-phosphate synthase 1 Human genes 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108010061833 Integrases Proteins 0.000 description 1
- 102100022843 Inward rectifier potassium channel 13 Human genes 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- 201000002287 Keratoconus Diseases 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241001484259 Lacuna Species 0.000 description 1
- 201000009709 Leber congenital amaurosis 11 Diseases 0.000 description 1
- 201000010480 Leber congenital amaurosis 13 Diseases 0.000 description 1
- 201000008886 Leber congenital amaurosis 14 Diseases 0.000 description 1
- 201000010472 Leber congenital amaurosis 7 Diseases 0.000 description 1
- 201000002502 Leber congenital amaurosis 8 Diseases 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 208000001344 Macular Edema Diseases 0.000 description 1
- 206010025415 Macular oedema Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 206010025476 Malabsorption Diseases 0.000 description 1
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 102100037817 Medium-wave-sensitive opsin 2 Human genes 0.000 description 1
- 102100030351 Membrane-associated phosphatidylinositol transfer protein 3 Human genes 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 241000699684 Meriones unguiculatus Species 0.000 description 1
- 206010063341 Metamorphopsia Diseases 0.000 description 1
- 208000002678 Mucopolysaccharidoses Diseases 0.000 description 1
- 206010056886 Mucopolysaccharidosis I Diseases 0.000 description 1
- 208000006550 Mydriasis Diseases 0.000 description 1
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 101000903581 Natronomonas pharaonis Halorhodopsin Proteins 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108091005461 Nucleic proteins Chemical group 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 101150046816 PRPH2 gene Proteins 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241000282576 Pan paniscus Species 0.000 description 1
- 201000010183 Papilledema Diseases 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108010003081 Peripherins Proteins 0.000 description 1
- 102000004590 Peripherins Human genes 0.000 description 1
- 241001291959 Phiala Species 0.000 description 1
- 241000233805 Phoenix Species 0.000 description 1
- 241000288935 Platyrrhini Species 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 241000282405 Pongo abelii Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 102100021231 Pre-mRNA-processing-splicing factor 8 Human genes 0.000 description 1
- 108010001267 Protein Subunits Proteins 0.000 description 1
- 102000002067 Protein Subunits Human genes 0.000 description 1
- 102100033154 Protein XRP2 Human genes 0.000 description 1
- 208000036575 RDH12-related recessive retinopathy Diseases 0.000 description 1
- 102000009572 RNA Polymerase II Human genes 0.000 description 1
- 108010009460 RNA Polymerase II Proteins 0.000 description 1
- 230000006819 RNA synthesis Effects 0.000 description 1
- 230000004570 RNA-binding Effects 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102100036240 Regulating synaptic membrane exocytosis protein 1 Human genes 0.000 description 1
- 102100033908 Retina and anterior neural fold homeobox protein 2 Human genes 0.000 description 1
- 208000037111 Retinal Hemorrhage Diseases 0.000 description 1
- 208000007135 Retinal Neovascularization Diseases 0.000 description 1
- 208000002367 Retinal Perforations Diseases 0.000 description 1
- 101710195150 Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma Proteins 0.000 description 1
- 201000007737 Retinal degeneration Diseases 0.000 description 1
- 206010057430 Retinal injury Diseases 0.000 description 1
- 206010038886 Retinal oedema Diseases 0.000 description 1
- 208000032400 Retinal pigmentation Diseases 0.000 description 1
- 102100028001 Retinaldehyde-binding protein 1 Human genes 0.000 description 1
- 206010038910 Retinitis Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 101710178616 Retinol dehydrogenase 12 Proteins 0.000 description 1
- 102100040756 Rhodopsin Human genes 0.000 description 1
- 102100039177 Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha Human genes 0.000 description 1
- 102100039174 Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta Human genes 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 101000733871 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L4-A Proteins 0.000 description 1
- 101000733875 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L4-B Proteins 0.000 description 1
- 241000555745 Sciuridae Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 208000020221 Short stature Diseases 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 208000014584 Specific learning disability Diseases 0.000 description 1
- 102100030257 Spermatogenesis-associated protein 7 Human genes 0.000 description 1
- 101000942604 Sphingomonas wittichii (strain DC-6 / KACC 16600) Chloroacetanilide N-alkylformylase, oxygenase component Proteins 0.000 description 1
- 208000010112 Spinocerebellar Degenerations Diseases 0.000 description 1
- 241000713675 Spumavirus Species 0.000 description 1
- 241000519995 Stachys sylvatica Species 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 101150079992 Timp3 gene Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- BGDKAVGWHJFAGW-UHFFFAOYSA-N Tropicamide Chemical compound C=1C=CC=CC=1C(CO)C(=O)N(CC)CC1=CC=NC=C1 BGDKAVGWHJFAGW-UHFFFAOYSA-N 0.000 description 1
- 102100029293 Tubby-related protein 1 Human genes 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 102100037930 Usherin Human genes 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 208000034699 Vitreous floaters Diseases 0.000 description 1
- 208000034698 Vitreous haemorrhage Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 101710135205 X-linked retinitis pigmentosa GTPase regulator-interacting protein 1 Proteins 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 208000004622 abetalipoproteinemia Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 238000003975 animal breeding Methods 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 210000002159 anterior chamber Anatomy 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 210000002565 arteriole Anatomy 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 201000004562 autosomal dominant cerebellar ataxia Diseases 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 239000003855 balanced salt solution Substances 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 229940064804 betadine Drugs 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 201000010018 blue color blindness Diseases 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 210000001775 bruch membrane Anatomy 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 108010018804 c-Mer Tyrosine Kinase Proteins 0.000 description 1
- 102000002717 c-Mer Tyrosine Kinase Human genes 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 229960004203 carnitine Drugs 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000002458 cell surface marker Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 210000003793 centrosome Anatomy 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
- 229960002023 chloroprocaine Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 210000003161 choroid Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 239000013024 dilution buffer Substances 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 230000000464 effect on transcription Effects 0.000 description 1
- 230000000463 effect on translation Effects 0.000 description 1
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007159 enucleation Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 210000000873 fovea centralis Anatomy 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- FBPFZTCFMRRESA-GUCUJZIJSA-N galactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-GUCUJZIJSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 210000004392 genitalia Anatomy 0.000 description 1
- 230000004313 glare Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000010370 hearing loss Effects 0.000 description 1
- 231100000888 hearing loss Toxicity 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 208000003215 hereditary nephritis Diseases 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 201000006318 hyperopia Diseases 0.000 description 1
- 230000004305 hyperopia Effects 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 229940065638 intron a Drugs 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 208000017476 juvenile neuronal ceroid lipofuscinosis Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 108010084957 lecithin-retinol acyltransferase Proteins 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 231100000875 loss of motor control Toxicity 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 201000010230 macular retinal edema Diseases 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000007885 magnetic separation Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 210000004088 microvessel Anatomy 0.000 description 1
- 206010028093 mucopolysaccharidosis Diseases 0.000 description 1
- 208000001491 myopia Diseases 0.000 description 1
- 230000004379 myopia Effects 0.000 description 1
- 201000003142 neovascular glaucoma Diseases 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000005157 neural retina Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 201000008051 neuronal ceroid lipofuscinosis Diseases 0.000 description 1
- 201000007607 neuronal ceroid lipofuscinosis 3 Diseases 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- UYDLBVPAAFVANX-UHFFFAOYSA-N octylphenoxy polyethoxyethanol Chemical class CC(C)(C)CC(C)(C)C1=CC=C(OCCOCCOCCOCCO)C=C1 UYDLBVPAAFVANX-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000012536 packaging technology Methods 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 238000004091 panning Methods 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 208000008016 pathologic nystagmus Diseases 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 210000003668 pericyte Anatomy 0.000 description 1
- 210000005047 peripherin Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 210000004694 pigment cell Anatomy 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 230000004983 pleiotropic effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 208000003580 polydactyly Diseases 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 208000007221 postaxial polydactyly Diseases 0.000 description 1
- 208000033468 postaxial type A1 polydactyly Diseases 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229960001371 proparacaine hydrochloride Drugs 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 238000001814 protein method Methods 0.000 description 1
- 201000003004 ptosis Diseases 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 201000000763 red color blindness Diseases 0.000 description 1
- 239000013643 reference control Substances 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 101150066583 rep gene Proteins 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 208000003345 retinal cone dystrophy 3A Diseases 0.000 description 1
- 230000004258 retinal degeneration Effects 0.000 description 1
- 201000011195 retinal edema Diseases 0.000 description 1
- 208000032253 retinal ischemia Diseases 0.000 description 1
- 230000004287 retinal location Effects 0.000 description 1
- 239000000790 retinal pigment Substances 0.000 description 1
- 210000000844 retinal pigment epithelial cell Anatomy 0.000 description 1
- 230000004250 retinal swelling Effects 0.000 description 1
- 210000001210 retinal vessel Anatomy 0.000 description 1
- 208000001571 retinitis pigmentosa 1 Diseases 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 208000027653 severe early-childhood-onset retinal dystrophy Diseases 0.000 description 1
- 229960002078 sevoflurane Drugs 0.000 description 1
- DFEYYRMXOJXZRJ-UHFFFAOYSA-N sevoflurane Chemical compound FCOC(C(F)(F)F)C(F)(F)F DFEYYRMXOJXZRJ-UHFFFAOYSA-N 0.000 description 1
- 230000004599 slow eye movement Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 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
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229960004791 tropicamide Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 208000012783 uncoordinated gait Diseases 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000004382 visual function Effects 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 208000030401 vitamin deficiency disease Diseases 0.000 description 1
- 208000020938 vitelliform macular dystrophy 2 Diseases 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 239000001052 yellow pigment Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/76—Viruses; Subviral particles; Bacteriophages
- A61K35/761—Adenovirus
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2800/00—Nucleic acids vectors
- C12N2800/24—Vectors characterised by the absence of particular element, e.g. selectable marker, viral origin of replication
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/30—Vector systems having a special element relevant for transcription being an enhancer not forming part of the promoter region
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/42—Vector systems having a special element relevant for transcription being an intron or intervening sequence for splicing and/or stability of RNA
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Virology (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Mycology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Cell Biology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461954330P | 2014-03-17 | 2014-03-17 | |
| US61/954,330 | 2014-03-17 | ||
| US201562127185P | 2015-03-02 | 2015-03-02 | |
| US62/127,185 | 2015-03-02 | ||
| PCT/US2015/021087 WO2015142941A1 (en) | 2014-03-17 | 2015-03-17 | Compositions and methods for enhanced gene expression in cone cells |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019143618A Division JP2019205465A (ja) | 2014-03-17 | 2019-08-05 | 錐体細胞における増強された遺伝子発現のための組成物および方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017510296A JP2017510296A (ja) | 2017-04-13 |
| JP2017510296A5 JP2017510296A5 (OSRAM) | 2018-04-26 |
| JP6689249B2 true JP6689249B2 (ja) | 2020-05-20 |
Family
ID=54068212
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017501086A Active JP6689249B2 (ja) | 2014-03-17 | 2015-03-17 | 錐体細胞における増強された遺伝子発現のための組成物および方法 |
| JP2019143618A Withdrawn JP2019205465A (ja) | 2014-03-17 | 2019-08-05 | 錐体細胞における増強された遺伝子発現のための組成物および方法 |
| JP2021205900A Pending JP2022037159A (ja) | 2014-03-17 | 2021-12-20 | 錐体細胞における増強された遺伝子発現のための組成物および方法 |
| JP2021205899A Pending JP2022037158A (ja) | 2014-03-17 | 2021-12-20 | 錐体細胞における増強された遺伝子発現のための組成物および方法 |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019143618A Withdrawn JP2019205465A (ja) | 2014-03-17 | 2019-08-05 | 錐体細胞における増強された遺伝子発現のための組成物および方法 |
| JP2021205900A Pending JP2022037159A (ja) | 2014-03-17 | 2021-12-20 | 錐体細胞における増強された遺伝子発現のための組成物および方法 |
| JP2021205899A Pending JP2022037158A (ja) | 2014-03-17 | 2021-12-20 | 錐体細胞における増強された遺伝子発現のための組成物および方法 |
Country Status (11)
| Country | Link |
|---|---|
| US (3) | US10000741B2 (OSRAM) |
| EP (2) | EP3800191B1 (OSRAM) |
| JP (4) | JP6689249B2 (OSRAM) |
| KR (2) | KR102537394B1 (OSRAM) |
| CN (2) | CN106414474B (OSRAM) |
| AU (3) | AU2015231439B2 (OSRAM) |
| CA (1) | CA2942776C (OSRAM) |
| ES (2) | ES3042252T3 (OSRAM) |
| IL (2) | IL259321B2 (OSRAM) |
| SG (2) | SG11201607738WA (OSRAM) |
| WO (1) | WO2015142941A1 (OSRAM) |
Families Citing this family (67)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120172419A1 (en) | 2009-09-15 | 2012-07-05 | Medical College Of Wisconsin Research Foundation Inc. | Reagents and methods for modulating cone photoreceptor activity |
| LT3254703T (lt) | 2011-04-22 | 2020-05-25 | The Regents Of The University Of California | Adenoasocijuoto viruso virionai su variantine kapside ir jų panaudojimo būdai |
| TWI775096B (zh) | 2012-05-15 | 2022-08-21 | 澳大利亞商艾佛蘭屈澳洲私營有限公司 | 使用腺相關病毒(aav)sflt-1治療老年性黃斑部退化(amd) |
| WO2014194132A1 (en) | 2013-05-31 | 2014-12-04 | The Regents Of The University Of California | Adeno-associated virus variants and methods of use thereof |
| CA2942776C (en) | 2014-03-17 | 2023-01-24 | Adverum Biotechnologies, Inc. | Polyneucleotide cassette and expression vector for expression of a gene in cone cells using truncated m-opsin promoter |
| KR20170137730A (ko) * | 2015-03-02 | 2017-12-13 | 애드베룸 바이오테크놀로지스, 인코포레이티드 | 망막 추상체에 폴리뉴클레오타이드의 유리체 내 전달을 위한 조성물 및 방법 |
| CN108474001B (zh) * | 2015-12-03 | 2022-04-08 | 弗里德里克·米谢尔生物医学研究所 | SynP160，用于基因在视杆光感受器中特异性表达的启动子 |
| ES2761328T3 (es) * | 2015-12-03 | 2020-05-19 | Friedrich Miescher Institute For Biomedical Res | SynP161, un promotor para la expresión específica de genes en fotorreceptores de bastón |
| RU2762747C2 (ru) | 2015-12-14 | 2021-12-22 | Зе Трастис Оф Зе Юниверсити Оф Пенсильвания | Генная терапия офтальмологических нарушений |
| GB2545763A (en) | 2015-12-23 | 2017-06-28 | Adverum Biotechnologies Inc | Mutant viral capsid libraries and related systems and methods |
| CN107287239B (zh) * | 2016-04-11 | 2020-09-22 | 厦门继景生物技术有限责任公司 | 一种用于视网膜色素变性的基因治疗载体及药物 |
| AU2017257169B2 (en) * | 2016-04-29 | 2021-07-08 | Adverum Biotechnologies, Inc. | Evasion of neutralizing antibodies by a recombinant adeno-associated virus |
| US12173305B2 (en) | 2016-05-26 | 2024-12-24 | University Of Iowa Research Foundation | cis and trans requirements for terminal resolution of human bocavirus 1 |
| DK3472317T3 (da) * | 2016-06-16 | 2022-05-23 | Adverum Biotechnologies Inc | Sammensætninger og fremgangsmåder til reduktion af okulær vaskularisation |
| CN110191954B (zh) | 2016-07-08 | 2024-05-14 | 宾夕法尼亚州大学信托人 | 用于治疗涉及rdh12的病症和疾病的方法和组合物 |
| KR20230039779A (ko) | 2016-07-29 | 2023-03-21 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 변이체 캡시드를 갖는 아데노-관련된 바이러스 비리온 및 이의 사용 방법 |
| EP3528785A4 (en) | 2016-10-19 | 2020-12-02 | Adverum Biotechnologies, Inc. | MODIFIED AAV CASPIDS AND USES THEREOF |
| EP3570895A1 (en) * | 2017-01-17 | 2019-11-27 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods of expressing a polynucleotide of interest in the cone photoreceptors |
| KR102616820B1 (ko) | 2017-03-17 | 2023-12-21 | 애드베룸 바이오테크놀로지스, 인코포레이티드 | 향상된 유전자 발현을 위한 조성물 및 방법 |
| JP2020519379A (ja) * | 2017-05-08 | 2020-07-02 | ラムダヴィジョン インコーポレイテッド | 網膜細胞を刺激し、視力喪失を処置するための方法 |
| JP7766393B2 (ja) | 2017-06-14 | 2025-11-10 | 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 | 眼疾患のための遺伝子療法 |
| CN110461368A (zh) | 2017-06-30 | 2019-11-15 | 加利福尼亚大学董事会 | 具有变异衣壳的腺相关病毒病毒体及其使用方法 |
| EP3676373A4 (en) | 2017-08-28 | 2021-06-09 | The Regents of The University of California | Adeno-associated virus capsid variants and methods of use thereof |
| DK3684423T5 (da) | 2017-09-20 | 2024-08-26 | 4D Molecular Therapeutics Inc | Adeno-associerede virusvariantcapsider og fremgangsmåder til anvendelse deraf |
| US11723988B2 (en) | 2017-10-20 | 2023-08-15 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods of expressing a polynucleotide of interest in the cone photoreceptors of a subject comprising the subretinal delivery of a therapeutically effective amount of a recombinant AAV9-derived vector |
| CN111417339A (zh) | 2017-11-13 | 2020-07-14 | 加利福尼亚大学董事会 | 用于增强视功能的组合物和方法 |
| EP3720460A1 (en) * | 2017-12-05 | 2020-10-14 | University of Washington | Compositions and methods for enhancing functional expression of therapeutic genes in photoreceptors |
| GB201800546D0 (en) * | 2018-01-12 | 2018-02-28 | Ucl Business Plc | Treatment |
| CA3091810A1 (en) * | 2018-03-02 | 2019-09-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Use of il-34 to treat retinal inflammation and neurodegeneration |
| CN109097364B (zh) * | 2018-09-03 | 2022-02-11 | 深圳广三系农业科技有限公司 | 一种植物胚乳特异性表达启动子pOsEnS100的鉴定和应用 |
| EP3893718A4 (en) | 2018-12-12 | 2022-11-09 | Tesseract Health, Inc. | BIOMETRIC IDENTIFICATION SYSTEMS AND RELATED DEVICES |
| WO2020167770A1 (en) * | 2019-02-11 | 2020-08-20 | President And Fellows Of Harvard College | Txnip and ldhb compositions and methods for the treatment of degenerative ocular diseases |
| US12270033B2 (en) | 2019-02-15 | 2025-04-08 | Exhaura, Ltd. | Dual leucine zipper kinase inhibitors for gene therapy |
| CA3137078A1 (en) * | 2019-04-15 | 2020-10-22 | University Of Iowa Research Foundation | Methods and compositions for transgene expression |
| WO2020214809A2 (en) * | 2019-04-19 | 2020-10-22 | University Of Massachusetts | Gene therapies for stargardt disease (abca4) |
| US11737665B2 (en) | 2019-06-21 | 2023-08-29 | Tesseract Health, Inc. | Multi-modal eye imaging with shared optical path |
| WO2021062012A1 (en) | 2019-09-25 | 2021-04-01 | Emory University | Use of klk10 and engineered derivatizations thereof |
| CA3154826A1 (en) * | 2019-10-17 | 2021-04-22 | Jonathan P. LING | Compositions and methods for using alternative splicing to control specificity of gene therapy |
| CA3165922A1 (en) | 2020-01-17 | 2021-07-22 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Gene therapy for treatment of crx-autosomal dominant retinopathies |
| US12257320B2 (en) | 2020-03-11 | 2025-03-25 | Massachusetts Eye And Ear Infirmary | Gene therapy for NMNAT1-associated retinal degeneration |
| US20230159609A1 (en) | 2020-04-10 | 2023-05-25 | Sorbonne Université | G-protein-gated-k+ channel-mediated enhancements in light sensitivity in rod-cone dystrophy (rcd) |
| CN111429547B (zh) * | 2020-04-27 | 2023-05-30 | 中国人民解放军空军工程大学 | 一种基于假同色搜索的异常色觉测试图合成方法 |
| CA3175905A1 (en) | 2020-04-27 | 2021-11-04 | David H. Kirn | Codon optimized gla genes and uses thereof |
| WO2022020548A2 (en) * | 2020-07-23 | 2022-01-27 | President And Fellows Of Harvard College | Variant txnip compositions and methods of use thereof for the treatment of degenerative ocular diseases |
| WO2022026632A2 (en) * | 2020-07-29 | 2022-02-03 | University Of Florida Research Foundation, Incorporated | Improved aav-mediated x-linked retinoschisis therapies |
| CN112062827B (zh) * | 2020-09-16 | 2022-10-21 | 中国人民解放军军事科学院军事医学研究院 | Cep55蛋白在调控纤毛去组装和制备纤毛相关疾病模型中的应用 |
| GB202102832D0 (en) * | 2021-02-26 | 2021-04-14 | Ip2Ipo Innovations Ltd | Retroviral vectors |
| US12385064B2 (en) * | 2021-03-26 | 2025-08-12 | Adverum Biotechnologies, Inc. | Intravitreal dosing for delivery of polynucleotides to retinal cones |
| GB202104611D0 (en) * | 2021-03-31 | 2021-05-12 | Univ Oxford Innovation Ltd | Gene therapy for retinal disease |
| US20230049217A1 (en) * | 2021-05-21 | 2023-02-16 | Novartis Ag | Compositions and methods for enhancing visual function |
| KR20240035759A (ko) | 2021-05-26 | 2024-03-18 | 스페어링비젼 | 막대세포-원추세포 이상증(rcd)에서 g-단백질-개폐-k+ 채널-매개 감광성 향상 |
| CN113408798B (zh) * | 2021-06-14 | 2022-03-29 | 华中师范大学 | 一种面向色觉异常人群的无障碍vr教学资源色彩优化方法 |
| KR102876040B1 (ko) | 2021-07-30 | 2025-10-23 | 주식회사 엘지에너지솔루션 | 이차 전지용 전극, 이의 제조방법, 및 상기 전극을 포함하는 이차 전지 |
| CA3231028A1 (en) * | 2021-09-06 | 2023-03-09 | Shaoran Wang | Treatment of rpe65-associated eye diseases and disorders |
| US20230338581A1 (en) | 2021-10-11 | 2023-10-26 | Sparingvision | G-protein-gated-k+ channel-mediated enhancements in light sensitivity in rod-cone dystrophy (rcd) |
| WO2023122804A1 (en) * | 2021-12-24 | 2023-06-29 | The Trustees Of The University Of Pennsylvania | Compositions and methods comprising a cardiac-specific promoter |
| WO2023205758A2 (en) * | 2022-04-22 | 2023-10-26 | West Virginia University Board of Governors on behalf of West Virginia University | Raav-cone opsin compositions and methods for treating blue cone monochromacy and color blindness |
| CN114848850B (zh) * | 2022-04-28 | 2023-12-15 | 武汉中眸生物科技有限责任公司 | Rs1基因在制备xlrs治疗剂中的应用及治疗剂 |
| CA3257440A1 (en) * | 2022-07-06 | 2024-01-11 | Adverum Biotechnologies, Inc. | COMPOSITIONS AND METHODS FOR THE TREATMENT OF ACHROMOTOPSY |
| TW202421773A (zh) * | 2022-09-30 | 2024-06-01 | 美商聖堤生物科技股份有限公司 | 用於光受體之細胞型特異性調控元件 |
| EP4357359A1 (en) | 2022-10-20 | 2024-04-24 | Sparingvision | G-protein-gated-k+ channel-mediated enhancements in light sensitivity in rod-cone dystrophy (rcd) |
| CN118791624A (zh) * | 2023-04-11 | 2024-10-18 | 苏州星明优健生物技术有限公司 | 用于治疗视网膜神经退行性疾病的新型gpcr嵌合视蛋白 |
| WO2025022144A1 (en) * | 2023-07-26 | 2025-01-30 | Sorbonne Universite | Chimeric promoter for targeted expression in aii amacrine cells |
| WO2025113432A1 (zh) * | 2023-11-27 | 2025-06-05 | 北京因诺惟康医药科技有限公司 | 一种用于治疗x染色体连锁视网膜劈裂症的基因药物 |
| CN120098992A (zh) * | 2023-12-05 | 2025-06-06 | 云舟生物科技(广州)股份有限公司 | 核酸分子及其作为特异启动子的应用 |
| CN118064572B (zh) * | 2024-03-15 | 2025-07-01 | 温州谱希基因科技有限公司 | 一种用于红绿色觉异常诊断的引物探针组合和试剂盒及其应用 |
| CN118562953A (zh) * | 2024-06-21 | 2024-08-30 | 复旦大学附属眼耳鼻喉科医院 | 检测opn1lw与opn1mw基因单倍体型的试剂在近视诊断试剂盒中的应用及产品 |
Family Cites Families (194)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US4874237A (en) | 1987-05-07 | 1989-10-17 | Lions Eye Inst. Of Western Australia | Electroretinogram apparatus |
| CA2002839C (en) | 1988-11-14 | 2000-10-10 | Neal S. Young | Parvovirus capsids |
| FR2643252B1 (fr) | 1989-02-21 | 1991-06-07 | Technomed Int Sa | Appareil de destruction selective de cellules incluant les tissus mous et les os a l'interieur du corps d'un etre vivant par implosion de bulles de gaz |
| US5112946A (en) | 1989-07-06 | 1992-05-12 | Repligen Corporation | Modified pf4 compositions and methods of use |
| US5436146A (en) | 1989-09-07 | 1995-07-25 | The Trustees Of Princeton University | Helper-free stocks of recombinant adeno-associated virus vectors |
| US6379885B1 (en) | 1989-09-14 | 2002-04-30 | Rijksuniversiteit Te Leiden | Human parvovirus B19 proteins and virus-like particles, their production and their use in diagnostic assays and vaccines |
| CA2096222C (en) | 1990-11-13 | 1998-12-29 | Stephen D. Lupton | Bifunctional selectable fusion genes |
| US5383917A (en) | 1991-07-05 | 1995-01-24 | Jawahar M. Desai | Device and method for multi-phase radio-frequency ablation |
| GB9206016D0 (en) | 1992-03-19 | 1992-04-29 | Sandoz Ltd | Improvements in or relating to organic compounds |
| ATE281469T1 (de) | 1993-03-25 | 2004-11-15 | Merck & Co Inc | Inhibitor des wachstumsfaktors für gefäss- endothelzellen |
| AU6953394A (en) | 1993-05-21 | 1994-12-20 | Targeted Genetics Corporation | Bifunctional selectable fusion genes based on the cytosine deaminase (cd) gene |
| US5814618A (en) | 1993-06-14 | 1998-09-29 | Basf Aktiengesellschaft | Methods for regulating gene expression |
| WO1995022618A1 (en) | 1994-02-22 | 1995-08-24 | Dana-Farber Cancer Institute | Nucleic acid delivery system, method of synthesis and uses thereof |
| US6551618B2 (en) | 1994-03-15 | 2003-04-22 | University Of Birmingham | Compositions and methods for delivery of agents for neuronal regeneration and survival |
| FR2718150B1 (fr) | 1994-03-29 | 1996-04-26 | Rhone Poulenc Rorer Sa | Virus recombinants, préparation et utilisation en thérapie génique. |
| US5639725A (en) | 1994-04-26 | 1997-06-17 | Children's Hospital Medical Center Corp. | Angiostatin protein |
| US5527533A (en) | 1994-10-27 | 1996-06-18 | Board Of Trustees Of The University Of Illinois | Method of retarding and ameliorating central nervous system and eye damage |
| US20020168342A1 (en) | 1994-11-03 | 2002-11-14 | Cell Genesys, Inc. | Novel adenoviral vectors, packaging cell lines, recombinant adenoviruses and methods |
| US6440425B1 (en) | 1995-05-01 | 2002-08-27 | Aventis Pasteur Limited | High molecular weight major outer membrane protein of moraxella |
| US6093570A (en) | 1995-06-07 | 2000-07-25 | The University Of North Carolina At Chapel Hill | Helper virus-free AAV production |
| US6040183A (en) | 1995-06-07 | 2000-03-21 | University Of North Carloina At Chapel Hill | Helper virus-free AAV production |
| US6001650A (en) | 1995-08-03 | 1999-12-14 | Avigen, Inc. | High-efficiency wild-type-free AAV helper functions |
| US6013516A (en) | 1995-10-06 | 2000-01-11 | The Salk Institute For Biological Studies | Vector and method of use for nucleic acid delivery to non-dividing cells |
| US5641749A (en) | 1995-11-29 | 1997-06-24 | Amgen Inc. | Method for treating retinal ganglion cell injury using glial cell line-derived neurothrophic factor (GDNF) protein product |
| US6096548A (en) | 1996-03-25 | 2000-08-01 | Maxygen, Inc. | Method for directing evolution of a virus |
| EP0927044A4 (en) | 1996-04-16 | 1999-09-08 | Immusol Inc | DEFINED TARGET VIRAL VECTORS |
| WO1998007435A1 (en) | 1996-08-20 | 1998-02-26 | The Regents Of The University Of California | Eye treatments using synthetic thyroid hormone compositions |
| CA2266419A1 (en) | 1996-09-24 | 1998-04-02 | Merck & Co., Inc. | Gene therapy for inhibition of angiogenesis |
| FR2756297B1 (fr) | 1996-11-22 | 1999-01-08 | Centre Nat Rech Scient | Procede de production de virus recombinants |
| US6153436A (en) * | 1997-01-10 | 2000-11-28 | The Board Of Trustees Of The University Of Arkansas | Method of gene delivery using wildtype adeno associated viral (AAV) vectors with insertions |
| AU728220B2 (en) | 1997-04-14 | 2001-01-04 | Cell Genesys, Inc. | Methods for increasing the efficiency of recombinant AAV product |
| AU7383298A (en) | 1997-05-13 | 1998-12-08 | Regents Of The University Of California, The | Novel antiangiogenic peptide agents and their therapeutic and diagnostic use |
| US6710036B2 (en) | 1997-07-25 | 2004-03-23 | Avigen, Inc. | Induction of immune response to antigens expressed by recombinant adeno-associated virus |
| US6458157B1 (en) | 1997-08-04 | 2002-10-01 | Suaning Gregg Joergen | Retinal stimulator |
| CA2303768C (en) | 1997-09-19 | 2009-11-24 | The Trustees Of The University Of Pennsylvania | Methods and vector constructs useful for production of recombinant aav |
| JPH11100327A (ja) | 1997-09-26 | 1999-04-13 | Toray Ind Inc | 網膜変性症治療剤 |
| AU9673998A (en) | 1997-10-01 | 1999-04-23 | G.D. Searle & Co. | Fusion proteins comprising an angiostatin moiety and their use in anti-tumor treatment |
| EP1690868A1 (en) | 1997-10-31 | 2006-08-16 | Maxygen, Inc. | Modification of virus tropism and host range by viral genome shuffling |
| US5994136A (en) | 1997-12-12 | 1999-11-30 | Cell Genesys, Inc. | Method and means for producing high titer, safe, recombinant lentivirus vectors |
| US6410300B1 (en) | 1998-01-12 | 2002-06-25 | The University Of North Carolina At Chapel Hill | Methods and formulations for mediating adeno-associated virus (AAV) attachment and infection and methods for purifying AAV |
| EP1045921A2 (en) | 1998-01-16 | 2000-10-25 | Chiron Corporation | Feline immunodeficiency virus gene therapy vectors |
| US6551795B1 (en) | 1998-02-18 | 2003-04-22 | Genome Therapeutics Corporation | Nucleic acid and amino acid sequences relating to pseudomonas aeruginosa for diagnostics and therapeutics |
| EP1061943B1 (en) | 1998-03-12 | 2002-10-23 | Genentech, Inc. | Use of fgf-5 polypeptides for preventing the death of retinal neurons and treating ocular diseases |
| DE19827457C1 (de) | 1998-06-19 | 2000-03-02 | Medigene Ag | Strukturprotein von AAV, seine Herstellung und Verwendung |
| US6593133B1 (en) | 1998-07-06 | 2003-07-15 | Nsgene A/S | Neurotrophic factors |
| JP2002528056A (ja) | 1998-08-28 | 2002-09-03 | デューク・ユニバーシティー | ＩＶａ２、１００Ｋ及び／又は末端前タンパク質配列における欠失型アデノウイルス |
| ATE294874T1 (de) | 1998-09-11 | 2005-05-15 | Univ California | Rekombinante adenovirus für gewebespezifische genexpression ins herz |
| NZ511037A (en) | 1998-09-17 | 2005-02-25 | Univ Florida | Methods for treatment of degenerative retinal diseases |
| US20040234505A1 (en) | 1998-09-23 | 2004-11-25 | Stuart Naylor | Polynucleotide constructs and uses thereof |
| DE69941905D1 (de) | 1998-11-10 | 2010-02-25 | Univ North Carolina | Virusvektoren und verfahren für ihre herstellung und verabreichung. |
| WO2000054813A2 (en) | 1999-03-15 | 2000-09-21 | 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 |
| US6498244B1 (en) | 1999-05-28 | 2002-12-24 | Cell Genesys, Inc. | Adeno-associated virus capsid immunologic determinants |
| US7070959B1 (en) | 1999-06-08 | 2006-07-04 | Regeneron Pharmaceuticals, Inc. | Modified chimeric polypeptides with improved pharmacokinetic properties |
| US7087411B2 (en) | 1999-06-08 | 2006-08-08 | Regeneron Pharmaceuticals, Inc. | Fusion protein capable of binding VEGF |
| US7306799B2 (en) | 1999-06-08 | 2007-12-11 | Regeneron Pharmaceuticals, Inc. | Use of VEGF inhibitors for treatment of eye disorders |
| US7314912B1 (en) | 1999-06-21 | 2008-01-01 | Medigene Aktiengesellschaft | AAv scleroprotein, production and use thereof |
| DE19933288A1 (de) | 1999-07-15 | 2001-01-18 | Medigene Ag | Strukturprotein von Adeno-assoziiertem Virus mit veränderter Antigenität, seine Herstellung und Verwendung |
| DE19933719A1 (de) | 1999-07-19 | 2001-01-25 | Medigene Ag | Strukturprotein in Adeno-assoziiertem Virus mit veränderten chromatographischen Eigenschaften, seine Herstellung und Verwendung |
| US8232081B2 (en) | 1999-09-21 | 2012-07-31 | Basf Se | Methods and microorganisms for production of panto-compounds |
| CA2387127A1 (en) | 1999-10-25 | 2001-05-17 | Therus Corporation | Use of focused ultrasound for vascular sealing |
| WO2002081628A2 (en) | 2001-04-05 | 2002-10-17 | Ribozyme Pharmaceuticals, Incorporated | Modulation of gene expression associated with inflammation proliferation and neurite outgrowth, using nucleic acid based technologies |
| US6855314B1 (en) | 2000-03-22 | 2005-02-15 | The United States Of America As Represented By The Department Of Health And Human Services | AAV5 vector for transducing brain cells and lung cells |
| WO2001078586A1 (en) | 2000-04-17 | 2001-10-25 | Stuart Graham | Method and apparatus for objective electrophysiological assessment of visual function |
| US6329181B1 (en) | 2000-08-07 | 2001-12-11 | Neurologix, Inc. | Helper functions for recombinant vector production |
| US7749492B2 (en) | 2001-01-05 | 2010-07-06 | Nationwide Children's Hospital, Inc. | AAV vectors and methods |
| US6962815B2 (en) | 2001-01-05 | 2005-11-08 | Children's Hopital Inc. | AAV2 vectors and methods |
| AU2002236988A1 (en) | 2001-02-06 | 2002-08-19 | Novartis Ag | Photodynamic therapy of occult choroidal neovascularization linked to age-related macular degeneration |
| US20040102765A1 (en) | 2001-03-27 | 2004-05-27 | Karsten Koenig | Method for the minimal-to non-invase optical treatment of tissues of the eye and for diagnosis thereof and device for carrying out said method |
| CA2442670A1 (en) | 2001-04-13 | 2002-10-24 | The Trustees Of The University Of Pennsylvania | Method of treating or retarding the development of blindness |
| JP2002363107A (ja) | 2001-06-04 | 2002-12-18 | Noriyuki Azuma | 色覚不全動物の色覚復元方法 |
| EP1412493B1 (en) | 2001-08-02 | 2011-10-05 | Institut Clayton De La Recherche | Methods and compositions relating to improved lentiviral vector production systems |
| US20030129203A1 (en) | 2001-08-27 | 2003-07-10 | Nautilus Biotech S.A. | Mutant recombinant adeno-associated viruses |
| US7647184B2 (en) | 2001-08-27 | 2010-01-12 | Hanall Pharmaceuticals, Co. Ltd | High throughput directed evolution by rational mutagenesis |
| US6723551B2 (en) | 2001-11-09 | 2004-04-20 | The United States Of America As Represented By The Department Of Health And Human Services | Production of adeno-associated virus in insect cells |
| SG168422A1 (en) | 2001-11-13 | 2011-02-28 | Univ Pennsylvania | A method of detecting and/or identifying adeno-associated virus (aav) sequences and isolating novel sequences identified thereby |
| US20050106558A1 (en) | 2001-12-21 | 2005-05-19 | Luca Perabo | Library of modified structural genes or capsid modified particles useful for the identification of viral clones with desired cell tropism |
| EP1490113A4 (en) | 2002-03-20 | 2007-05-02 | Univ Florida | RAAV VECTOR COMPOSITIONS AND METHOD FOR TREATING CHOROIDAL NEOVASCULARIZATION |
| WO2003089612A2 (en) | 2002-04-17 | 2003-10-30 | University Of Florida Research Foundation, Inc. | IMPROVED rAAV VECTORS |
| WO2003093436A2 (en) | 2002-04-30 | 2003-11-13 | University Of Florida | Treatment for phenylketonuria |
| AU2003223775A1 (en) | 2002-04-30 | 2003-11-17 | Duke University | Adeno-associated viral vectors and methods for their production from hybrid adenovirus and for their use |
| US7254489B2 (en) | 2002-05-31 | 2007-08-07 | Microsoft Corporation | Systems, methods and apparatus for reconstructing phylogentic trees |
| US8304233B2 (en) | 2002-06-04 | 2012-11-06 | Poetic Genetics, Llc | Methods of unidirectional, site-specific integration into a genome, compositions and kits for practicing the same |
| US7220577B2 (en) | 2002-08-28 | 2007-05-22 | University Of Florida Research Foundation, Inc. | Modified AAV |
| GB0220467D0 (en) | 2002-09-03 | 2002-10-09 | Oxford Biomedica Ltd | Composition |
| WO2004079332A2 (en) | 2003-03-04 | 2004-09-16 | National Institute Of Advanced Industrial Science And Technology | Composition and method for increasing efficiency of introduction of target substance into cell |
| US20070172460A1 (en) | 2003-03-19 | 2007-07-26 | Jurgen Kleinschmidt | Random peptide library displayed on aav vectors |
| WO2004108922A2 (en) | 2003-04-25 | 2004-12-16 | The Trustees Of The University Of Pennsylvania | Use of aav comprising a capsid protein from aav7 or aav8 for the delivery of genes encoding apoprotein a or e genes to the liver |
| EP1486567A1 (en) | 2003-06-11 | 2004-12-15 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Improved adeno-associated virus (AAV) vector for gene therapy |
| PL2357189T3 (pl) | 2003-06-19 | 2017-08-31 | Genzyme Corporation | Wiriony AAV o zmniejszonej immunoreaktywności i ich zastosowanie |
| JP2007524622A (ja) | 2003-06-23 | 2007-08-30 | エイアンドジー ファーマスーティカルズ インコーポレイテッド | 抗癌治療に対する腫瘍細胞の感受性を回復させてアポトーシスを誘導するための組成物及び方法 |
| US9441244B2 (en) | 2003-06-30 | 2016-09-13 | The Regents Of The University Of California | Mutant adeno-associated virus virions and methods of use thereof |
| US9233131B2 (en) | 2003-06-30 | 2016-01-12 | The Regents Of The University Of California | Mutant adeno-associated virus virions and methods of use thereof |
| AU2004276316A1 (en) | 2003-09-24 | 2005-04-07 | The Board Of Trustees Of The Leland Stanford Junior University | IGF-1 instructs multipotent adult CNS neural stem cells to an oligodendroglial lineage |
| EP3910063A1 (en) | 2003-09-30 | 2021-11-17 | The Trustees of The University of Pennsylvania | Adeno-associated virus (aav) clades, sequences, vectors containing same, and uses therefor |
| US20060166363A1 (en) | 2004-01-27 | 2006-07-27 | Sergei Zolotukhin | Modified baculovirus expression system for production of pseudotyped rAAV vector |
| US7427396B2 (en) | 2004-06-03 | 2008-09-23 | Genzyme Corporation | AAV vectors for gene delivery to the lung |
| EP2324848A3 (en) | 2004-10-21 | 2011-09-14 | Genentech, Inc. | Method for treating intraocular neovascular diseases |
| SI1809750T1 (sl) * | 2004-11-08 | 2012-08-31 | Chromagenics Bv | Izbira gostiteljskih celic, ki imajo visok nivo izraĹľanja proteina |
| CN101124328A (zh) | 2004-12-15 | 2008-02-13 | 北卡罗来纳查佩尔山大学 | 嵌合载体 |
| US20100172871A1 (en) | 2005-02-17 | 2010-07-08 | Flannery John G | Muller Cell Specific Gene Therapy |
| US7922670B2 (en) | 2005-02-24 | 2011-04-12 | Warren Jones | System and method for quantifying and mapping visual salience |
| EP3409296A1 (en) | 2005-04-07 | 2018-12-05 | The Trustees of the University of Pennsylvania | Method of increasing the function of an aav vector |
| US20060234347A1 (en) | 2005-04-13 | 2006-10-19 | Harding Thomas C | Targeting multiple angiogenic pathways for cancer therapy using soluble tyrosine kinase receptors |
| PL1945779T3 (pl) | 2005-10-20 | 2013-08-30 | Uniqure Ip Bv | Ulepszone wektory AAV produkowane w komórkach owadzich |
| WO2007084773A2 (en) | 2006-01-20 | 2007-07-26 | University Of North Carolina At Chapel Hill | Enhanced production of infectious parvovirus vectors in insect cells |
| WO2007089632A2 (en) | 2006-01-27 | 2007-08-09 | The University Of North Carolina At Chapel Hill | Heparin and heparan sulfate binding chimeric vectors |
| US20070190028A1 (en) | 2006-02-13 | 2007-08-16 | Jihong Qu | Method and apparatus for heat or electromagnetic control of gene expression |
| US8118752B2 (en) | 2006-02-16 | 2012-02-21 | The Board Of Trustees Of The University Of Illinois | Apparatus and methods for mapping retinal function |
| US7384145B2 (en) | 2006-02-16 | 2008-06-10 | The Board Of Trustees Of The University Of Illinois | Mapping retinal function using corneal electrode array |
| EP2007795B1 (en) | 2006-03-30 | 2016-11-16 | The Board Of Trustees Of The Leland Stanford Junior University | Aav capsid proteins |
| US8216575B2 (en) | 2006-03-31 | 2012-07-10 | Chengdu Kanghong Biotechnologies Co., Ltd. | Inhibition of neovascularization with a soluble chimeric protein comprising VEGF FLT-1 and KDR domains |
| CA2685900A1 (en) | 2006-05-04 | 2007-11-15 | Wayne State University | Restoration of visual responses by in vivo delivery of rhodopsin nucleic acids |
| CA2651194A1 (en) | 2006-05-04 | 2007-11-15 | Fondation Ophthalmologique Aldolphe De Rothschild | Methods for treating neovascular diseases |
| EP2029746B1 (en) | 2006-06-12 | 2012-07-04 | Exegenics, Inc., D/b/a Opko Health, Inc. | Compositions and methods for sirna inhibition of angiogenesis |
| GB0612096D0 (en) | 2006-06-19 | 2006-07-26 | Greater Glasgow Nhs Board | Functional imaging of the retina |
| CA2655957C (en) | 2006-06-21 | 2016-05-03 | Amsterdam Molecular Therapeutics (Amt) B.V. | Vectors with modified initiation codon for the translation of aav-rep78 useful for production of aav in insect cells |
| CN101313366A (zh) | 2006-06-27 | 2008-11-26 | 株式会社爱德万测试 | 半导体试验装置以及半导体存储器的试验方法 |
| EP2061891B1 (en) | 2006-08-24 | 2012-04-11 | Virovek, Inc. | Expression in insect cells of genes with overlapping open reading frames, methods and compositions therefor |
| CN1966082B (zh) | 2006-11-03 | 2010-06-30 | 许瑞安 | 一种防治结直肠癌的基因药物及其制备方法和用途 |
| WO2008098310A1 (en) | 2007-02-16 | 2008-08-21 | Objectivision Limited | Stimulus method for multifocal visual evoked potential |
| US9725485B2 (en) | 2012-05-15 | 2017-08-08 | University Of Florida Research Foundation, Inc. | AAV vectors with high transduction efficiency and uses thereof for gene therapy |
| BRPI0810172A2 (pt) | 2007-04-13 | 2014-10-14 | Catalyst Biosciences Inc | Polipeptídeos de fator vii modificado e seus usos |
| EP1985708B1 (en) | 2007-04-27 | 2015-04-15 | Universität Rostock | Selective targeting of viruses to neural precursor cells |
| EP1995309A1 (en) | 2007-05-21 | 2008-11-26 | Vivalis | Recombinant protein production in avian EBx® cells |
| WO2008150459A1 (en) | 2007-05-30 | 2008-12-11 | The Trustees Of The University Of Pennsylvania | A method for transducing cells with primary cilia |
| US8540369B2 (en) | 2007-08-16 | 2013-09-24 | The Research Foundation Of State University Of New York | Led variable light source |
| US8518037B2 (en) | 2007-10-30 | 2013-08-27 | Boston Scientific Scimed, Inc. | Radiofrequency ablation device |
| WO2009073551A2 (en) | 2007-11-30 | 2009-06-11 | Scarab Genomics Llc | Lac expression system |
| CN102007209B (zh) | 2008-02-19 | 2013-11-13 | 阿姆斯特丹分子治疗(Amt)股份有限公司 | 细小病毒rep和cap蛋白在昆虫细胞中的表达优化 |
| CN101951925A (zh) | 2008-02-20 | 2011-01-19 | 建新公司 | 血管发生抑制 |
| US20100081707A1 (en) | 2008-02-21 | 2010-04-01 | Ali Robin R | Devices and methods for delivering polynucleotides into retinal cells of the macula and fovea |
| ITFI20080081A1 (it) | 2008-04-18 | 2009-10-19 | Strumenti Oftalmici C S O S R | Procedimento e sistema per la registrazione di risposte elettrofunzionali erg, perg e vep multifocali in tempo reale |
| US8632764B2 (en) | 2008-04-30 | 2014-01-21 | University Of North Carolina At Chapel Hill | Directed evolution and in vivo panning of virus vectors |
| EP2910637A1 (en) | 2008-05-20 | 2015-08-26 | University of Florida Research Foundation, Inc. | Vectors for delivery of light-sensitive proteins and methods of use |
| ES2330826B1 (es) | 2008-06-04 | 2010-07-26 | Proyecto De Biomedicina Cima, S.L. | Sistema para empaquetamiento de adenovirus de alta capacidad. |
| US20110171262A1 (en) | 2008-06-17 | 2011-07-14 | Andrew Christian Bakker | Parvoviral capsid with incorporated gly-ala repeat region |
| JP5491511B2 (ja) | 2008-10-07 | 2014-05-14 | ブラッコ・シュイス・ソシエテ・アノニム | 抗ポリマー抗体およびそれと結合するリポソームまたは微小胞を含むターゲッティング構築物 |
| WO2010093784A2 (en) | 2009-02-11 | 2010-08-19 | The University Of North Carolina At Chapel Hill | Modified virus vectors and methods of making and using the same |
| EP2403867B1 (en) | 2009-03-04 | 2019-05-22 | Deutsches Krebsforschungszentrum | Assembly activating protein (aap) and its use for the manufacture of parvovirus particles essential consisting of vp3 |
| WO2010114948A2 (en) | 2009-04-02 | 2010-10-07 | University Of Florida Research Foundation, Inc. | An inducible system for highly efficient production of recombinant adeno-associated virus (raav) vectors |
| CN101532024A (zh) | 2009-04-30 | 2009-09-16 | 许瑞安 | 一种用于基因治疗的新型细胞特异性内含microRNA结合序列的基因HAAVmir |
| WO2010138263A2 (en) | 2009-05-28 | 2010-12-02 | University Of Massachusetts | Novel aav 's and uses thereof |
| TWI466158B (zh) | 2009-07-03 | 2014-12-21 | Univ Lunghwa Sci & Technology | 電漿測量裝置、電漿系統及測量電漿特性之方法 |
| EP2287323A1 (en) | 2009-07-31 | 2011-02-23 | Association Institut de Myologie | Widespread gene delivery to the retina using systemic administration of AAV vectors |
| EP2292781A1 (en) | 2009-08-17 | 2011-03-09 | Genethon | Baculovirus-based production of biopharmaceuticals free of contaminating baculoviral virions |
| US20120172419A1 (en) * | 2009-09-15 | 2012-07-05 | Medical College Of Wisconsin Research Foundation Inc. | Reagents and methods for modulating cone photoreceptor activity |
| US20110270256A1 (en) | 2009-09-24 | 2011-11-03 | Medicinelodge, Inc. Dba Imds Co-Innovation | Surgical rasp with radiofrequency ablation |
| ES2683695T3 (es) | 2010-01-12 | 2018-09-27 | The University Of North Carolina At Chapel Hill | Repeticiones terminales invertidas restrictivas para vectores virales |
| US9228174B2 (en) | 2010-03-11 | 2016-01-05 | Uniqure Ip B.V. | Mutated rep encoding sequences for use in AAV production |
| WO2011117258A2 (en) | 2010-03-22 | 2011-09-29 | Association Institut De Myologie | Methods of increasing efficiency of vector penetration of target tissue |
| WO2011126808A2 (en) | 2010-03-29 | 2011-10-13 | The Trustees Of The University Of Pennsylvania | Pharmacologically induced transgene ablation system |
| WO2011122950A1 (en) | 2010-04-01 | 2011-10-06 | Amsterdam Molecular Therapeutics (Amt) Ip B.V. | Monomeric duplex aav vectors |
| WO2011137344A2 (en) | 2010-04-30 | 2011-11-03 | Lpath, Inc. | Anti-s1p antibody treatment of patients with ocular disease |
| CN201704771U (zh) | 2010-04-30 | 2011-01-12 | 陈福环 | 无水箱节水型抽水马桶 |
| US8663624B2 (en) | 2010-10-06 | 2014-03-04 | The Regents Of The University Of California | Adeno-associated virus virions with variant capsid and methods of use thereof |
| US20110052678A1 (en) | 2010-11-05 | 2011-03-03 | Shantha Totada R | Method for treating age related macular degeneration |
| JP6092782B2 (ja) | 2010-11-16 | 2017-03-08 | エクセリミューン， インコーポレイテッド | 組換えタンパク質の製造方法 |
| CN103608455B (zh) * | 2011-01-07 | 2019-01-15 | 应用遗传科技公司 | 用于治疗色盲和其它疾病的启动子、表达盒、载体、药盒和方法 |
| LT3254703T (lt) | 2011-04-22 | 2020-05-25 | The Regents Of The University Of California | Adenoasocijuoto viruso virionai su variantine kapside ir jų panaudojimo būdai |
| EP2748185A1 (en) | 2011-08-24 | 2014-07-02 | The Board of Trustees of The Leland Stanford Junior University | New aav capsid proteins for nucleic acid transfer |
| AU2012327236B2 (en) | 2011-10-28 | 2016-11-10 | University Of Florida Research Foundation, Inc. | Chimeric promoter for cone photoreceptor targeted gene therapy |
| JP6385920B2 (ja) | 2012-05-09 | 2018-09-05 | オレゴン ヘルス アンド サイエンス ユニバーシティー | アデノ随伴ウイルスプラスミド及びベクター |
| TWI775096B (zh) | 2012-05-15 | 2022-08-21 | 澳大利亞商艾佛蘭屈澳洲私營有限公司 | 使用腺相關病毒(aav)sflt-1治療老年性黃斑部退化(amd) |
| WO2013188316A1 (en) | 2012-06-11 | 2013-12-19 | Avalanche Biotechnologies, Inc. | Optical regulation of gene expression in the retina |
| JP6363958B2 (ja) | 2012-12-25 | 2018-07-25 | タカラバイオ株式会社 | Ａａｖ変異体 |
| CA2912525A1 (en) * | 2013-05-16 | 2014-11-20 | Applied Genetic Technologies Corporation | Promoters, expression cassettes, vectors, kits, and methods for the treatment of achromatopsia and other diseases |
| JP6670743B2 (ja) | 2013-05-29 | 2020-03-25 | セレクティスＣｅｌｌｅｃｔｉｓ | Ｉｉ型ｃｒｉｓｐｒシステムにおける新規のコンパクトなｃａｓ９足場 |
| WO2014194132A1 (en) | 2013-05-31 | 2014-12-04 | The Regents Of The University Of California | Adeno-associated virus variants and methods of use thereof |
| ES2716615T3 (es) | 2013-06-28 | 2019-06-13 | Inst Nat Sante Rech Med | Métodos para expresar un polinucleótido de interés en la retina de un sujeto |
| US20150025939A1 (en) | 2013-07-18 | 2015-01-22 | Somnath Chatterjee | Company Centric Social Media Platfonn for Content Sharing aud Tracking |
| EP3564379A1 (en) | 2013-09-13 | 2019-11-06 | California Institute of Technology | Selective recovery |
| EP3633041A3 (en) | 2013-09-26 | 2020-07-29 | University of Florida Research Foundation, Inc. | Synthetic combinatorial aav capsid library for targeted gene therapy |
| NZ758025A (en) | 2013-10-11 | 2022-07-01 | Massachusetts Eye & Ear Infirmary | Methods of predicting ancestral virus sequences and uses thereof |
| EP3057990B1 (en) | 2013-10-18 | 2019-09-04 | Regeneron Pharmaceuticals, Inc. | Compositions comprising a combination of a vegf antagonist and an anti-ctla-4 antibody |
| EP3113787B1 (en) | 2014-03-04 | 2019-12-04 | University of Florida Research Foundation, Inc. | Improved raav vectors and methods for transduction of photoreceptors and rpe cells |
| CA2942776C (en) | 2014-03-17 | 2023-01-24 | Adverum Biotechnologies, Inc. | Polyneucleotide cassette and expression vector for expression of a gene in cone cells using truncated m-opsin promoter |
| LT3137497T (lt) | 2014-05-02 | 2021-07-26 | Genzyme Corporation | Aav vektoriai, skirti tinklainės ir cns genų terapijai |
| CA2951707A1 (en) | 2014-06-10 | 2015-12-17 | Massachusetts Institute Of Technology | Method for gene editing |
| KR20170137730A (ko) | 2015-03-02 | 2017-12-13 | 애드베룸 바이오테크놀로지스, 인코포레이티드 | 망막 추상체에 폴리뉴클레오타이드의 유리체 내 전달을 위한 조성물 및 방법 |
| HRP20201225T1 (hr) | 2015-03-06 | 2020-11-13 | Massachusetts Eye & Ear Infirmary | Terapije poboljšavanja gena kod nasljedne degeneracije mrežnice uzrokovanu mutacijama u genu prpf31 |
| WO2016154344A1 (en) | 2015-03-24 | 2016-09-29 | The Regents Of The University Of California | Adeno-associated virus variants and methods of use thereof |
| WO2017023724A1 (en) | 2015-07-31 | 2017-02-09 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of aadc deficiency |
| GB2545763A (en) | 2015-12-23 | 2017-06-28 | Adverum Biotechnologies Inc | Mutant viral capsid libraries and related systems and methods |
| AU2017257169B2 (en) | 2016-04-29 | 2021-07-08 | Adverum Biotechnologies, Inc. | Evasion of neutralizing antibodies by a recombinant adeno-associated virus |
| CA3022667A1 (en) | 2016-05-03 | 2017-11-09 | Adverum Biotechnologies, Inc. | Organotypic pig retina culture system |
| MX2018013463A (es) | 2016-05-13 | 2019-07-04 | 4D Molecular Therapeutics Inc | Capsides variantes de virus adenoasociados y metodos de uso de las mismas. |
| DK3472317T3 (da) | 2016-06-16 | 2022-05-23 | Adverum Biotechnologies Inc | Sammensætninger og fremgangsmåder til reduktion af okulær vaskularisation |
| PT3795181T (pt) | 2016-06-16 | 2025-11-05 | Adverum Biotechnologies Inc | Tratamento de dmi com utilização da variante aav2 com aflibercept |
| EP3528785A4 (en) | 2016-10-19 | 2020-12-02 | Adverum Biotechnologies, Inc. | MODIFIED AAV CASPIDS AND USES THEREOF |
| AU2018227483A1 (en) | 2017-02-28 | 2019-09-12 | Adverum Biotechnologies, Inc. | Modified AAV capsids and uses thereof |
| KR102616820B1 (ko) | 2017-03-17 | 2023-12-21 | 애드베룸 바이오테크놀로지스, 인코포레이티드 | 향상된 유전자 발현을 위한 조성물 및 방법 |
| EP3676373A4 (en) | 2017-08-28 | 2021-06-09 | The Regents of The University of California | Adeno-associated virus capsid variants and methods of use thereof |
-
2015
- 2015-03-17 CA CA2942776A patent/CA2942776C/en active Active
- 2015-03-17 ES ES20189453T patent/ES3042252T3/es active Active
- 2015-03-17 CN CN201580024713.4A patent/CN106414474B/zh active Active
- 2015-03-17 SG SG11201607738WA patent/SG11201607738WA/en unknown
- 2015-03-17 EP EP20189453.2A patent/EP3800191B1/en active Active
- 2015-03-17 CN CN202011526173.9A patent/CN112626125A/zh active Pending
- 2015-03-17 SG SG10201810150UA patent/SG10201810150UA/en unknown
- 2015-03-17 KR KR1020217024851A patent/KR102537394B1/ko active Active
- 2015-03-17 JP JP2017501086A patent/JP6689249B2/ja active Active
- 2015-03-17 EP EP15765668.7A patent/EP3119798B1/en active Active
- 2015-03-17 ES ES15765668T patent/ES2822551T3/es active Active
- 2015-03-17 KR KR1020167028411A patent/KR102288849B1/ko active Active
- 2015-03-17 US US14/660,657 patent/US10000741B2/en active Active
- 2015-03-17 IL IL259321A patent/IL259321B2/en unknown
- 2015-03-17 WO PCT/US2015/021087 patent/WO2015142941A1/en not_active Ceased
- 2015-03-17 AU AU2015231439A patent/AU2015231439B2/en active Active
-
2016
- 2016-09-11 IL IL247756A patent/IL247756B/en active IP Right Review Request
-
2018
- 2018-05-18 US US15/984,085 patent/US11248214B2/en active Active
-
2019
- 2019-08-05 JP JP2019143618A patent/JP2019205465A/ja not_active Withdrawn
-
2020
- 2020-02-10 AU AU2020200948A patent/AU2020200948B2/en active Active
-
2021
- 2021-12-20 JP JP2021205900A patent/JP2022037159A/ja active Pending
- 2021-12-20 US US17/556,847 patent/US12275959B2/en active Active
- 2021-12-20 JP JP2021205899A patent/JP2022037158A/ja active Pending
-
2022
- 2022-02-03 AU AU2022200708A patent/AU2022200708A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US12275959B2 (en) | Compositions and methods for enhanced gene expression in cone cells | |
| US20210388030A1 (en) | Compositions and methods for intravitreal delivery of polynucleotides to retinal cones | |
| JP2025503495A (ja) | 錐体光受容体細胞を産生するためのプロセス | |
| HK40049243A (en) | Compositions and methods for enhanced gene expression in cone cells | |
| HK1229816B (en) | Compositions and methods for enhanced gene expression in cone cells | |
| HK1229816A1 (en) | Compositions and methods for enhanced gene expression in cone cells | |
| NZ724403B2 (en) | Compositions and methods for enhanced gene expression in cone cells | |
| JP2025500979A (ja) | 光受容体細胞のインビボリプログラミング |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161116 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180315 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20180315 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190205 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190425 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20190625 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190805 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20191227 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200309 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200401 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200407 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6689249 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |