IL301647A - Adeno-associated viruses for ocular delivery of gene therapy - Google Patents
Adeno-associated viruses for ocular delivery of gene therapyInfo
- Publication number
- IL301647A IL301647A IL301647A IL30164723A IL301647A IL 301647 A IL301647 A IL 301647A IL 301647 A IL301647 A IL 301647A IL 30164723 A IL30164723 A IL 30164723A IL 301647 A IL301647 A IL 301647A
- Authority
- IL
- Israel
- Prior art keywords
- seq
- capsid
- aav
- aav9
- tissue
- Prior art date
Links
- 241000702421 Dependoparvovirus Species 0.000 title claims description 18
- 238000012384 transportation and delivery Methods 0.000 title description 21
- 238000001415 gene therapy Methods 0.000 title description 11
- 210000000234 capsid Anatomy 0.000 claims description 350
- 210000001519 tissue Anatomy 0.000 claims description 197
- 210000004027 cell Anatomy 0.000 claims description 194
- 108090000565 Capsid Proteins Proteins 0.000 claims description 120
- 102100023321 Ceruloplasmin Human genes 0.000 claims description 120
- 108700019146 Transgenes Proteins 0.000 claims description 98
- 241001164825 Adeno-associated virus - 8 Species 0.000 claims description 93
- 238000000034 method Methods 0.000 claims description 89
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 77
- 238000010361 transduction Methods 0.000 claims description 59
- 230000026683 transduction Effects 0.000 claims description 58
- 239000013608 rAAV vector Substances 0.000 claims description 49
- 239000008194 pharmaceutical composition Substances 0.000 claims description 45
- 238000006467 substitution reaction Methods 0.000 claims description 44
- 208000022873 Ocular disease Diseases 0.000 claims description 41
- 239000000203 mixture Substances 0.000 claims description 41
- 230000001225 therapeutic effect Effects 0.000 claims description 41
- 230000014509 gene expression Effects 0.000 claims description 37
- 241001655883 Adeno-associated virus - 1 Species 0.000 claims description 31
- 210000001585 trabecular meshwork Anatomy 0.000 claims description 30
- 210000004240 ciliary body Anatomy 0.000 claims description 28
- 210000001328 optic nerve Anatomy 0.000 claims description 28
- 241001164823 Adeno-associated virus - 7 Species 0.000 claims description 26
- 210000000554 iris Anatomy 0.000 claims description 25
- 241000580270 Adeno-associated virus - 4 Species 0.000 claims description 23
- 238000004806 packaging method and process Methods 0.000 claims description 23
- 241000202702 Adeno-associated virus - 3 Species 0.000 claims description 22
- 241001634120 Adeno-associated virus - 5 Species 0.000 claims description 22
- 241000972680 Adeno-associated virus - 6 Species 0.000 claims description 22
- 230000002207 retinal effect Effects 0.000 claims description 22
- 239000013607 AAV vector Substances 0.000 claims description 20
- 150000007523 nucleic acids Chemical class 0.000 claims description 20
- 210000004087 cornea Anatomy 0.000 claims description 16
- 108020004707 nucleic acids Proteins 0.000 claims description 14
- 102000039446 nucleic acids Human genes 0.000 claims description 14
- 230000001105 regulatory effect Effects 0.000 claims description 13
- 239000011159 matrix material Substances 0.000 claims description 11
- 125000003729 nucleotide group Chemical group 0.000 claims description 10
- 239000002773 nucleotide Substances 0.000 claims description 9
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims description 8
- 241000702423 Adeno-associated virus - 2 Species 0.000 claims description 8
- 229920002674 hyaluronan Polymers 0.000 claims description 8
- 229960003160 hyaluronic acid Drugs 0.000 claims description 8
- 208000010412 Glaucoma Diseases 0.000 claims description 7
- 206010046851 Uveitis Diseases 0.000 claims description 7
- 230000001413 cellular effect Effects 0.000 claims description 7
- 208000015181 infectious disease Diseases 0.000 claims description 7
- 230000002458 infectious effect Effects 0.000 claims description 7
- 241000958487 Adeno-associated virus 3B Species 0.000 claims 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 145
- 238000003780 insertion Methods 0.000 description 102
- 230000037431 insertion Effects 0.000 description 102
- 239000013598 vector Substances 0.000 description 101
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 63
- 239000003795 chemical substances by application Substances 0.000 description 52
- 210000001508 eye Anatomy 0.000 description 50
- 235000001014 amino acid Nutrition 0.000 description 48
- 108020004414 DNA Proteins 0.000 description 42
- 229940024606 amino acid Drugs 0.000 description 42
- 150000001413 amino acids Chemical class 0.000 description 42
- 238000002347 injection Methods 0.000 description 41
- 239000007924 injection Substances 0.000 description 41
- 239000002245 particle Substances 0.000 description 41
- 108090000623 proteins and genes Proteins 0.000 description 41
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 38
- 241000699670 Mus sp. Species 0.000 description 35
- 230000008499 blood brain barrier function Effects 0.000 description 35
- 210000001218 blood-brain barrier Anatomy 0.000 description 35
- 210000001525 retina Anatomy 0.000 description 35
- 238000004458 analytical method Methods 0.000 description 32
- 210000004556 brain Anatomy 0.000 description 32
- 208000035475 disorder Diseases 0.000 description 32
- 241001465754 Metazoa Species 0.000 description 31
- 201000010099 disease Diseases 0.000 description 31
- 239000012634 fragment Substances 0.000 description 27
- 239000005090 green fluorescent protein Substances 0.000 description 27
- 230000000069 prophylactic effect Effects 0.000 description 27
- 239000000427 antigen Substances 0.000 description 26
- 108091007433 antigens Proteins 0.000 description 26
- 102000036639 antigens Human genes 0.000 description 26
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 25
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 25
- 238000011282 treatment Methods 0.000 description 25
- 239000003814 drug Substances 0.000 description 24
- 102000004169 proteins and genes Human genes 0.000 description 24
- 235000018102 proteins Nutrition 0.000 description 23
- 125000000539 amino acid group Chemical group 0.000 description 19
- 210000003786 sclera Anatomy 0.000 description 19
- 230000008685 targeting Effects 0.000 description 18
- 241000282567 Macaca fascicularis Species 0.000 description 17
- 229940124597 therapeutic agent Drugs 0.000 description 17
- 230000010415 tropism Effects 0.000 description 17
- 102000004196 processed proteins & peptides Human genes 0.000 description 16
- 239000000523 sample Substances 0.000 description 16
- 238000011529 RT qPCR Methods 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- 238000012986 modification Methods 0.000 description 14
- 230000004048 modification Effects 0.000 description 14
- 238000007481 next generation sequencing Methods 0.000 description 14
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 14
- 241000699666 Mus <mouse, genus> Species 0.000 description 13
- 210000003161 choroid Anatomy 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 13
- 238000003556 assay Methods 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 238000011887 Necropsy Methods 0.000 description 10
- 238000000338 in vitro Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 208000003098 Ganglion Cysts Diseases 0.000 description 9
- 208000005400 Synovial Cyst Diseases 0.000 description 9
- 210000000695 crystalline len Anatomy 0.000 description 9
- 210000003734 kidney Anatomy 0.000 description 9
- 230000002093 peripheral effect Effects 0.000 description 9
- 101150044789 Cap gene Proteins 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000004113 cell culture Methods 0.000 description 8
- 238000009826 distribution Methods 0.000 description 8
- 108020001507 fusion proteins Proteins 0.000 description 8
- 102000037865 fusion proteins Human genes 0.000 description 8
- 230000001965 increasing effect Effects 0.000 description 8
- 230000010354 integration Effects 0.000 description 8
- 210000004185 liver Anatomy 0.000 description 8
- 230000005100 tissue tropism Effects 0.000 description 8
- 241000701161 unidentified adenovirus Species 0.000 description 8
- 241000700605 Viruses Species 0.000 description 7
- 238000010171 animal model Methods 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 238000013270 controlled release Methods 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 210000004379 membrane Anatomy 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 238000001543 one-way ANOVA Methods 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- 230000003612 virological effect Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 208000024304 Choroidal Effusions Diseases 0.000 description 6
- 108091092584 GDNA Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 108060001084 Luciferase Proteins 0.000 description 6
- 241000288906 Primates Species 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000009792 diffusion process Methods 0.000 description 6
- 239000003937 drug carrier Substances 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 210000004072 lung Anatomy 0.000 description 6
- 208000002780 macular degeneration Diseases 0.000 description 6
- 239000006228 supernatant Substances 0.000 description 6
- 241000282412 Homo Species 0.000 description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 description 5
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 5
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 5
- 210000000411 amacrine cell Anatomy 0.000 description 5
- 230000008827 biological function Effects 0.000 description 5
- 238000010276 construction Methods 0.000 description 5
- 210000002216 heart Anatomy 0.000 description 5
- 210000002287 horizontal cell Anatomy 0.000 description 5
- 238000003364 immunohistochemistry Methods 0.000 description 5
- 238000009540 indirect ophthalmoscopy Methods 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- 210000000608 photoreceptor cell Anatomy 0.000 description 5
- 210000003497 sciatic nerve Anatomy 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 210000003462 vein Anatomy 0.000 description 5
- 241000649044 Adeno-associated virus 9 Species 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241000282693 Cercopithecidae Species 0.000 description 4
- 206010011906 Death Diseases 0.000 description 4
- 102100035426 DnaJ homolog subfamily B member 7 Human genes 0.000 description 4
- 101100285903 Drosophila melanogaster Hsc70-2 gene Proteins 0.000 description 4
- 101100178718 Drosophila melanogaster Hsc70-4 gene Proteins 0.000 description 4
- 101100178723 Drosophila melanogaster Hsc70-5 gene Proteins 0.000 description 4
- 108010008165 Etanercept Proteins 0.000 description 4
- 101000804114 Homo sapiens DnaJ homolog subfamily B member 7 Proteins 0.000 description 4
- 101150090950 Hsc70-1 gene Proteins 0.000 description 4
- 239000005089 Luciferase Substances 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 101100150366 Schizosaccharomyces pombe (strain 972 / ATCC 24843) sks2 gene Proteins 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 229960002964 adalimumab Drugs 0.000 description 4
- 229960002833 aflibercept Drugs 0.000 description 4
- 108010081667 aflibercept Proteins 0.000 description 4
- 230000000288 anti-kallikrein effect Effects 0.000 description 4
- 229960000397 bevacizumab Drugs 0.000 description 4
- 229950000025 brolucizumab Drugs 0.000 description 4
- 229960003115 certolizumab pegol Drugs 0.000 description 4
- 229950001565 clazakizumab Drugs 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 210000002889 endothelial cell Anatomy 0.000 description 4
- 229960000403 etanercept Drugs 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 229960001743 golimumab Drugs 0.000 description 4
- 229960000598 infliximab Drugs 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 229950005287 lanadelumab Drugs 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 229950010006 olokizumab Drugs 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 210000001672 ovary Anatomy 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 229960003876 ranibizumab Drugs 0.000 description 4
- 229950007085 ravulizumab Drugs 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- 210000000844 retinal pigment epithelial cell Anatomy 0.000 description 4
- 229950006348 sarilumab Drugs 0.000 description 4
- 229940060041 satralizumab Drugs 0.000 description 4
- 229960003323 siltuximab Drugs 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 229950009054 tesidolumab Drugs 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 229960003989 tocilizumab Drugs 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- 241000649045 Adeno-associated virus 10 Species 0.000 description 3
- 241000649046 Adeno-associated virus 11 Species 0.000 description 3
- 241000649047 Adeno-associated virus 12 Species 0.000 description 3
- 241000300529 Adeno-associated virus 13 Species 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 238000011740 C57BL/6 mouse Methods 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 241000287828 Gallus gallus Species 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 3
- 208000001344 Macular Edema Diseases 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 108091081024 Start codon Proteins 0.000 description 3
- 241000282887 Suidae Species 0.000 description 3
- 241000519996 Teucrium chamaedrys Species 0.000 description 3
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 3
- 239000003708 ampul Substances 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
- 230000002146 bilateral effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 210000004958 brain cell Anatomy 0.000 description 3
- 210000004899 c-terminal region Anatomy 0.000 description 3
- 230000004700 cellular uptake Effects 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000009977 dual effect Effects 0.000 description 3
- 229960002224 eculizumab Drugs 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 210000000981 epithelium Anatomy 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 229920000669 heparin Polymers 0.000 description 3
- 210000001320 hippocampus Anatomy 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 229960003299 ketamine Drugs 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 239000008176 lyophilized powder Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000010232 migration assay Methods 0.000 description 3
- 238000009126 molecular therapy Methods 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 210000001577 neostriatum Anatomy 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 210000004498 neuroglial cell Anatomy 0.000 description 3
- 230000003472 neutralizing effect Effects 0.000 description 3
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 101150066583 rep gene Proteins 0.000 description 3
- 210000003994 retinal ganglion cell Anatomy 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 229950006094 sirukumab Drugs 0.000 description 3
- 210000002027 skeletal muscle Anatomy 0.000 description 3
- 210000000278 spinal cord Anatomy 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- UPXRTVAIJMUAQR-UHFFFAOYSA-N 4-(9h-fluoren-9-ylmethoxycarbonylamino)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1C(C(O)=O)N(C(=O)OC(C)(C)C)CC1NC(=O)OCC1C2=CC=CC=C2C2=CC=CC=C21 UPXRTVAIJMUAQR-UHFFFAOYSA-N 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 2
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- XZWYTXMRWQJBGX-VXBMVYAYSA-N FLAG peptide Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)CC1=CC=C(O)C=C1 XZWYTXMRWQJBGX-VXBMVYAYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 108010000521 Human Growth Hormone Proteins 0.000 description 2
- 102000002265 Human Growth Hormone Human genes 0.000 description 2
- 239000000854 Human Growth Hormone Substances 0.000 description 2
- 102100021244 Integral membrane protein GPR180 Human genes 0.000 description 2
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- 206010025415 Macular oedema Diseases 0.000 description 2
- 241000702623 Minute virus of mice Species 0.000 description 2
- 210000005156 Müller Glia Anatomy 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- LGCMKPRGGJRYGM-UHFFFAOYSA-N Osalmid Chemical compound C1=CC(O)=CC=C1NC(=O)C1=CC=CC=C1O LGCMKPRGGJRYGM-UHFFFAOYSA-N 0.000 description 2
- 102100026459 POU domain, class 3, transcription factor 2 Human genes 0.000 description 2
- 101710133394 POU domain, class 3, transcription factor 2 Proteins 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038934 Retinopathy proliferative Diseases 0.000 description 2
- 241000714474 Rous sarcoma virus Species 0.000 description 2
- 208000027073 Stargardt disease Diseases 0.000 description 2
- 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 2
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 206010064930 age-related macular degeneration Diseases 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 210000003484 anatomy Anatomy 0.000 description 2
- 210000001742 aqueous humor Anatomy 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 108010006025 bovine growth hormone Proteins 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000007012 clinical effect Effects 0.000 description 2
- 201000007254 color blindness Diseases 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000003511 endothelial effect Effects 0.000 description 2
- 208000030533 eye disease Diseases 0.000 description 2
- 238000002073 fluorescence micrograph Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 238000010362 genome editing Methods 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 210000001308 heart ventricle Anatomy 0.000 description 2
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 2
- 229960001008 heparin sodium Drugs 0.000 description 2
- 238000011532 immunohistochemical staining Methods 0.000 description 2
- 238000001114 immunoprecipitation Methods 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 229960002725 isoflurane Drugs 0.000 description 2
- 229960004184 ketamine hydrochloride Drugs 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 210000005244 lower chamber Anatomy 0.000 description 2
- 201000010230 macular retinal edema Diseases 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 108091070501 miRNA Proteins 0.000 description 2
- 239000002679 microRNA Substances 0.000 description 2
- 210000000663 muscle cell Anatomy 0.000 description 2
- 210000003098 myoblast Anatomy 0.000 description 2
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 2
- 239000013646 rAAV2 vector Substances 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 239000011347 resin Substances 0.000 description 2
- 229920005989 resin Polymers 0.000 description 2
- 208000004644 retinal vein occlusion Diseases 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 230000031998 transcytosis Effects 0.000 description 2
- 229960004791 tropicamide Drugs 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 210000004127 vitreous body Anatomy 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- 208000036443 AIPL1-related retinopathy Diseases 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
- 239000004475 Arginine Substances 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 102000009039 Axonemal Dyneins Human genes 0.000 description 1
- 108010049197 Axonemal Dyneins Proteins 0.000 description 1
- 201000001321 Bardet-Biedl syndrome Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 102100024522 Bladder cancer-associated protein Human genes 0.000 description 1
- 101150110835 Blcap gene Proteins 0.000 description 1
- 108091033409 CRISPR Proteins 0.000 description 1
- 238000010354 CRISPR gene editing Methods 0.000 description 1
- 101100348617 Candida albicans (strain SC5314 / ATCC MYA-2876) NIK1 gene Proteins 0.000 description 1
- 241001432959 Chernes Species 0.000 description 1
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 1
- 208000033810 Choroidal dystrophy Diseases 0.000 description 1
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000006992 Color Vision Defects Diseases 0.000 description 1
- 208000036693 Color-vision disease Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 206010058202 Cystoid macular oedema Diseases 0.000 description 1
- 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 1
- 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 1
- 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 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010012667 Diabetic glaucoma Diseases 0.000 description 1
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 1
- 206010012692 Diabetic uveitis Diseases 0.000 description 1
- 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 1
- 208000001351 Epiretinal Membrane Diseases 0.000 description 1
- 108010020195 FLAG peptide Proteins 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 201000008808 Fibrosarcoma Diseases 0.000 description 1
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101100412102 Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) rec2 gene Proteins 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 208000032087 Hereditary Leber Optic Atrophy Diseases 0.000 description 1
- 201000002563 Histoplasmosis Diseases 0.000 description 1
- 101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 0.000 description 1
- 101000729271 Homo sapiens Retinoid isomerohydrolase Proteins 0.000 description 1
- 101000640899 Homo sapiens Solute carrier family 12 member 2 Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 206010021143 Hypoxia Diseases 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
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 208000010038 Ischemic Optic Neuropathy Diseases 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-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
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 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
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 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
- 208000032420 Latent Infection Diseases 0.000 description 1
- 206010056715 Laurence-Moon-Bardet-Biedl syndrome Diseases 0.000 description 1
- 201000003533 Leber congenital amaurosis Diseases 0.000 description 1
- 201000000639 Leber hereditary optic neuropathy Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-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
- 208000031471 Macular fibrosis Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000010164 Multifocal Choroiditis Diseases 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010030924 Optic ischaemic neuropathy Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 101100493740 Oryza sativa subsp. japonica BC10 gene Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 241000701945 Parvoviridae Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 102000018120 Recombinases Human genes 0.000 description 1
- 108010091086 Recombinases Proteins 0.000 description 1
- 206010038848 Retinal detachment Diseases 0.000 description 1
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
- 102100031176 Retinoid isomerohydrolase Human genes 0.000 description 1
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
- 101100007329 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS1 gene Proteins 0.000 description 1
- 101100221606 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS7 gene Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 101710172711 Structural protein Proteins 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
- -1 TWEENTM Substances 0.000 description 1
- 206010043189 Telangiectasia Diseases 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 102100026143 Transferrin receptor protein 2 Human genes 0.000 description 1
- 101710145355 Transferrin receptor protein 2 Proteins 0.000 description 1
- 208000031861 Tritanopia Diseases 0.000 description 1
- 208000014769 Usher Syndromes Diseases 0.000 description 1
- 208000029977 White Dot Syndromes Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 201000000761 achromatopsia Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000023564 acute macular neuroretinopathy Diseases 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 201000007058 anterior ischemic optic neuropathy Diseases 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229950000847 ascrinvacumab Drugs 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 201000010018 blue color blindness Diseases 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 210000000692 cap cell Anatomy 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 229950005629 carotuximab Drugs 0.000 description 1
- 210000004534 cecum Anatomy 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 201000005667 central retinal vein occlusion Diseases 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 208000003571 choroideremia Diseases 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 201000006754 cone-rod dystrophy Diseases 0.000 description 1
- 208000006623 congenital stationary night blindness Diseases 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 210000003792 cranial nerve Anatomy 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 201000010206 cystoid macular edema Diseases 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229960004253 dexmedetomidine Drugs 0.000 description 1
- HRLIOXLXPOHXTA-NSHDSACASA-N dexmedetomidine Chemical compound C1([C@@H](C)C=2C(=C(C)C=CC=2)C)=CN=C[N]1 HRLIOXLXPOHXTA-NSHDSACASA-N 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 201000011190 diabetic macular edema Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 208000037771 disease arising from reactivation of latent virus Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 102000013035 dynein heavy chain Human genes 0.000 description 1
- 108060002430 dynein heavy chain Proteins 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 208000024519 eye neoplasm Diseases 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000007667 floating Methods 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 238000012224 gene deletion Methods 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 238000003197 gene knockdown Methods 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012510 hollow fiber Substances 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 229960000027 human factor ix Drugs 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000002991 immunohistochemical analysis Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229950005015 inebilizumab Drugs 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 238000002743 insertional mutagenesis Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 210000001630 jejunum Anatomy 0.000 description 1
- 210000000629 knee joint Anatomy 0.000 description 1
- 210000004561 lacrimal apparatus Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000002647 laser therapy Methods 0.000 description 1
- 229940055661 lecanemab Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012160 loading buffer Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000005065 mining Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 230000000869 mutational effect Effects 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 208000008795 neuromyelitis optica Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 201000008106 ocular cancer Diseases 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000007918 pathogenicity Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 229940124531 pharmaceutical excipient 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
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000004853 protein function Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 201000000763 red color blindness Diseases 0.000 description 1
- 201000000757 red-green color blindness Diseases 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 230000004283 retinal dysfunction Effects 0.000 description 1
- 201000007714 retinoschisis Diseases 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000011451 sequencing strategy Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- SQVRNKJHWKZAKO-OQPLDHBCSA-N sialic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)OC1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-OQPLDHBCSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000020183 skimmed milk Nutrition 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 229950007874 solanezumab Drugs 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000013595 supernatant sample Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 208000009056 telangiectasis Diseases 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000440 toxicity profile Toxicity 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002463 transducing effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000006107 tyrosine sulfation Effects 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 230000001982 uveitic effect Effects 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000000080 wetting agent 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/0008—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
- A61K48/0025—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid
- A61K48/0041—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid the non-active part being polymeric
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
- A61K48/0058—Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- 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
- C12N2750/14122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14171—Demonstrated in vivo effect
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Virology (AREA)
- Biophysics (AREA)
- Ophthalmology & Optometry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063088982P | 2020-10-07 | 2020-10-07 | |
| US202163187197P | 2021-05-11 | 2021-05-11 | |
| PCT/US2021/054008 WO2022076711A2 (en) | 2020-10-07 | 2021-10-07 | Adeno-associated viruses for ocular delivery of gene therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL301647A true IL301647A (en) | 2023-05-01 |
Family
ID=78483550
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL301647A IL301647A (en) | 2020-10-07 | 2021-10-07 | Adeno-associated viruses for ocular delivery of gene therapy |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20230381341A1 (enExample) |
| EP (1) | EP4225777A2 (enExample) |
| JP (1) | JP2023545722A (enExample) |
| KR (1) | KR20230082614A (enExample) |
| AU (1) | AU2021356667A1 (enExample) |
| CA (1) | CA3193697A1 (enExample) |
| IL (1) | IL301647A (enExample) |
| MX (1) | MX2023003699A (enExample) |
| WO (1) | WO2022076711A2 (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023060272A2 (en) * | 2021-10-07 | 2023-04-13 | Regenxbio Inc. | Recombinant adeno-associated viruses for cns tropic delivery |
| TW202345913A (zh) | 2022-04-06 | 2023-12-01 | 美商銳進科斯生物股份有限公司 | 用於脈絡膜上投與之調配物諸如凝膠調配物 |
| TW202404651A (zh) | 2022-04-06 | 2024-02-01 | 美商銳進科斯生物股份有限公司 | 用於脈絡膜上投與之調配物諸如形成聚集體之調配物 |
| US20260034246A1 (en) * | 2022-05-03 | 2026-02-05 | Regenxbio Inc. | Vectorized anti-complement antibodies and complement agents and administration thereof |
| WO2023215807A1 (en) * | 2022-05-03 | 2023-11-09 | Regenxbio Inc. | VECTORIZED ANTI-TNF-α INHIBITORS FOR OCULAR INDICATIONS |
| EP4532517A1 (en) * | 2022-05-31 | 2025-04-09 | Mount Spec Investments Pty Ltd | Modified adeno-associated virus capsid proteins and methods thereof |
| EP4540270A2 (en) * | 2022-06-14 | 2025-04-23 | Vectory B.V. | Recombinant aav capsid proteins |
| US20260055144A1 (en) * | 2022-08-24 | 2026-02-26 | Regenxbio Inc. | Recombinant adeno-associated viruses and uses thereof |
| AU2024206221A1 (en) * | 2023-01-05 | 2025-07-03 | Emugen Therapeutics Llc | Retro-aav and use in treating neurodegenerative diseases |
| WO2024238853A1 (en) * | 2023-05-16 | 2024-11-21 | Regenxbio Inc. | Adeno-associated viruses for ocular delivery of gene therapy |
| WO2024238867A1 (en) * | 2023-05-16 | 2024-11-21 | Regenxbio Inc. | Vectorized anti-complement antibodies and administration thereof |
| TW202548025A (zh) * | 2024-04-08 | 2025-12-16 | 美商銳進科斯生物股份有限公司 | 載體化抗補體抗體與補體劑及其投與 |
| CN119039401B (zh) * | 2024-08-19 | 2025-04-11 | 广州派真生物技术有限公司 | 腺相关病毒突变体及其应用 |
| WO2026047120A1 (en) * | 2024-08-28 | 2026-03-05 | Medizinische Hochschule Hannover | Aav viral vectors targeting the inner ear and medical treatment of the inner ear using said vectors |
Family Cites Families (43)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0092918B1 (en) | 1982-04-22 | 1988-10-19 | Imperial Chemical Industries Plc | Continuous release formulations |
| US5128326A (en) | 1984-12-06 | 1992-07-07 | Biomatrix, Inc. | Drug delivery systems based on hyaluronans derivatives thereof and their salts and methods of producing same |
| AU6430190A (en) | 1989-10-10 | 1991-05-16 | Pitman-Moore, Inc. | Sustained release composition for macromolecular proteins |
| CA2071867A1 (en) | 1989-11-06 | 1991-05-07 | Edith Mathiowitz | Method for producing protein microspheres |
| US5912015A (en) | 1992-03-12 | 1999-06-15 | Alkermes Controlled Therapeutics, Inc. | Modulated release from biocompatible polymers |
| ATE252894T1 (de) | 1995-01-05 | 2003-11-15 | Univ Michigan | Oberflächen-modifizierte nanopartikel und verfahren für ihre herstellung und verwendung |
| WO1997007788A2 (en) | 1995-08-31 | 1997-03-06 | Alkermes Controlled Therapeutics, Inc. | Composition for sustained release of an agent |
| US6156303A (en) * | 1997-06-11 | 2000-12-05 | University Of Washington | Adeno-associated virus (AAV) isolates and AAV vectors derived therefrom |
| US5989463A (en) | 1997-09-24 | 1999-11-23 | Alkermes Controlled Therapeutics, Inc. | Methods for fabricating polymer-based controlled release devices |
| SE512663C2 (sv) | 1997-10-23 | 2000-04-17 | Biogram Ab | Inkapslingsförfarande för aktiv substans i en bionedbrytbar polymer |
| CA2379166C (en) | 1999-08-09 | 2013-03-26 | Targeted Genetics Corporation | Enhancement of expression of a single-stranded, heterologous nucleotide sequence from recombinant viral vectors by designing the sequence such that it forms instrastrand base pairs |
| MX359371B (es) | 2001-11-13 | 2018-09-25 | Univ Pennsylvania | Un metodo para detectar y/o identificar secuencias del virus adeno-asociado y aislamiento de secuencias novedosas identificadas de ese modo. |
| PT1453547T (pt) | 2001-12-17 | 2016-12-28 | Univ Pennsylvania | Sequências do vírus adeno-associado (aav) do serotipo 8, vetores contendo as mesmas, e utilizações destas |
| EP2345731B1 (en) | 2003-09-30 | 2015-10-21 | The Trustees of the University of Pennsylvania | Adeno-associated virus (AAV) clades, sequences, vectors containing same, and uses thereof |
| US7183969B2 (en) | 2004-12-22 | 2007-02-27 | Raytheon Company | System and technique for calibrating radar arrays |
| ES2525067T3 (es) | 2005-04-07 | 2014-12-17 | The Trustees Of The University Of Pennsylvania | Método de incremento de la función de un vector de AAV |
| JP4495210B2 (ja) | 2005-06-09 | 2010-06-30 | パナソニック株式会社 | 振幅誤差補償装置及び直交度誤差補償装置 |
| JP2011512156A (ja) | 2008-02-19 | 2011-04-21 | アムステルダム モレキュラー セラピューティクス ビー．ブイ． | 昆虫細胞におけるパルボウイルスｒｅｐ及びｃａｐタンパク質の発現の最適化 |
| EP2425000B1 (en) | 2009-04-30 | 2019-02-20 | The Trustees Of The University Of Pennsylvania | Compositions for targeting conducting airway cells comprising adeno-associated virus constructs |
| US8734809B2 (en) | 2009-05-28 | 2014-05-27 | University Of Massachusetts | AAV's and uses thereof |
| US8927514B2 (en) | 2010-04-30 | 2015-01-06 | City Of Hope | Recombinant adeno-associated vectors for targeted treatment |
| US8628966B2 (en) | 2010-04-30 | 2014-01-14 | City Of Hope | CD34-derived recombinant adeno-associated vectors for stem cell transduction and systemic therapeutic gene transfer |
| WO2012057363A1 (ja) | 2010-10-27 | 2012-05-03 | 学校法人自治医科大学 | 神経系細胞への遺伝子導入のためのアデノ随伴ウイルスビリオン |
| WO2012109570A1 (en) | 2011-02-10 | 2012-08-16 | The University Of North Carolina At Chapel Hill | Viral vectors with modified transduction profiles and methods of making and using the same |
| CN105755044A (zh) | 2011-04-22 | 2016-07-13 | 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 |
| ES2857773T5 (es) | 2011-08-24 | 2024-06-04 | Univ Leland Stanford Junior | Nuevas proteínas de la cápside de AAV para la transferencia de ácidos nucleicos |
| WO2013170078A1 (en) | 2012-05-09 | 2013-11-14 | Oregon Health & Science University | Adeno associated virus plasmids and vectors |
| CA2905952A1 (en) | 2013-03-13 | 2014-10-02 | The Children's Hospital Of Philadelphia | Adeno-associated virus vectors and methods of use thereof |
| MX388221B (es) | 2013-04-20 | 2025-03-19 | Res Institute At Nationwide Children´S Hospital | ADMINISTRACIÓN DE VIRUS ADENO-ASOCIADO RECOMBINANTE DE CONSTRUCCIONES DE POLINUCLÉOTIDOS U7snRNA DIRIGIDA AL EXÓN 2. |
| IL297919A (en) | 2013-07-22 | 2023-01-01 | Childrens Hospital Philadelphia | Variant aav and compositions, methods and uses for gene transfer to cells, organs and tissues |
| ES2739288T3 (es) | 2013-09-13 | 2020-01-30 | California Inst Of Techn | Recuperación selectiva |
| CN106232618A (zh) | 2013-10-11 | 2016-12-14 | 马萨诸塞眼科耳科诊所 | 预测祖先病毒序列的方法及其用途 |
| GB201403684D0 (en) * | 2014-03-03 | 2014-04-16 | King S College London | Vector |
| AU2015229381B2 (en) * | 2014-03-11 | 2019-11-07 | University Of Florida Research Foundation, Inc. | Use of AAV-expressed M013 protein as an anti-inflammatory therapeutic |
| WO2015164757A1 (en) | 2014-04-25 | 2015-10-29 | Oregon Health & Science University | Methods of viral neutralizing antibody epitope mapping |
| EP3151866B1 (en) | 2014-06-09 | 2023-03-08 | Voyager Therapeutics, Inc. | Chimeric capsids |
| PL4012035T3 (pl) * | 2014-09-16 | 2025-03-24 | Genzyme Corporation | Wektory wirusowe związane z adenowirusami do leczenia jaskry miocylinowej (myoc) |
| AU2015320694B2 (en) | 2014-09-24 | 2021-11-11 | City Of Hope | Adeno-associated virus vector variants for high efficiency genome editing and methods thereof |
| JP6665466B2 (ja) | 2015-09-26 | 2020-03-13 | 日亜化学工業株式会社 | 半導体発光素子及びその製造方法 |
| WO2017070491A1 (en) | 2015-10-23 | 2017-04-27 | Applied Genetic Technologies Corporation | Ophthalmic formulations |
| CA3040179A1 (en) | 2016-10-19 | 2018-04-26 | Adverum Biotechnologies, Inc. | Modified aav capsids and uses thereof |
| TW202102526A (zh) * | 2019-04-04 | 2021-01-16 | 美商銳進科斯生物股份有限公司 | 重組腺相關病毒及其用途 |
| CA3144986A1 (en) * | 2019-06-27 | 2020-12-30 | University Of Florida Research Foundation, Incorporated | Enhancing aav-mediated transduction of ocular tissues with hyaluronic acid |
-
2021
- 2021-10-07 MX MX2023003699A patent/MX2023003699A/es unknown
- 2021-10-07 US US18/030,706 patent/US20230381341A1/en active Pending
- 2021-10-07 KR KR1020237010842A patent/KR20230082614A/ko active Pending
- 2021-10-07 JP JP2023521279A patent/JP2023545722A/ja active Pending
- 2021-10-07 IL IL301647A patent/IL301647A/en unknown
- 2021-10-07 AU AU2021356667A patent/AU2021356667A1/en not_active Abandoned
- 2021-10-07 CA CA3193697A patent/CA3193697A1/en active Pending
- 2021-10-07 WO PCT/US2021/054008 patent/WO2022076711A2/en not_active Ceased
- 2021-10-07 EP EP21801765.5A patent/EP4225777A2/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2023545722A (ja) | 2023-10-31 |
| MX2023003699A (es) | 2023-04-21 |
| EP4225777A2 (en) | 2023-08-16 |
| AU2021356667A9 (en) | 2025-03-13 |
| KR20230082614A (ko) | 2023-06-08 |
| CA3193697A1 (en) | 2022-04-14 |
| WO2022076711A2 (en) | 2022-04-14 |
| WO2022076711A3 (en) | 2022-06-02 |
| US20230381341A1 (en) | 2023-11-30 |
| AU2021356667A1 (en) | 2023-06-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7619958B2 (ja) | 組換えアデノ随伴ウイルス及びその使用 | |
| US20230381341A1 (en) | Adeno-associated viruses for ocular delivery of gene therapy | |
| US20250001006A1 (en) | Recombinant adeno-associated viruses for targeted delivery | |
| WO2022076750A2 (en) | Recombinant adeno-associated viruses for cns or muscle delivery | |
| US20230042103A1 (en) | Engineered nucleic acid regulatory element and methods of uses thereof | |
| EP4442698A1 (en) | Modified aav capsid protein and use thereof | |
| US20260055144A1 (en) | Recombinant adeno-associated viruses and uses thereof | |
| WO2023201308A1 (en) | Gene therapy for treating an ocular disease | |
| WO2023201277A1 (en) | Recombinant adeno-associated viruses for cns tropic delivery | |
| US20230374541A1 (en) | Recombinant adeno-associated viruses for cns or muscle delivery | |
| CN116568815A (zh) | 用于基因疗法的眼部递送的腺相关病毒 | |
| WO2024238853A1 (en) | Adeno-associated viruses for ocular delivery of gene therapy | |
| WO2025217214A2 (en) | Recombinant adeno-associated viruses and uses thereof | |
| EP4413019A2 (en) | Recombinant adeno-associated viruses for cns tropic delivery | |
| WO2025073297A1 (zh) | 表达抗vegf融合蛋白的aav病毒载体及其用途 | |
| TW202423974A (zh) | 一種感染視網膜的aav載體、阿達木單抗及其應用 | |
| HK40111920A (en) | Modified aav capsid protein and use thereof | |
| WO2024216244A2 (en) | Targeting aav capsids, methods of manufacturing and using same |