JP7420710B2 - 組換えaav9由来ベクターの治療有効量の網膜下送達を含む、対象の錐体視細胞において目的のポリヌクレオチドを発現させる方法 - Google Patents
組換えaav9由来ベクターの治療有効量の網膜下送達を含む、対象の錐体視細胞において目的のポリヌクレオチドを発現させる方法 Download PDFInfo
- Publication number
- JP7420710B2 JP7420710B2 JP2020522014A JP2020522014A JP7420710B2 JP 7420710 B2 JP7420710 B2 JP 7420710B2 JP 2020522014 A JP2020522014 A JP 2020522014A JP 2020522014 A JP2020522014 A JP 2020522014A JP 7420710 B2 JP7420710 B2 JP 7420710B2
- Authority
- JP
- Japan
- Prior art keywords
- polynucleotide
- interest
- cone
- seq
- composition
- 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
- 102000040430 polynucleotide Human genes 0.000 title claims description 83
- 108091033319 polynucleotide Proteins 0.000 title claims description 83
- 239000002157 polynucleotide Substances 0.000 title claims description 83
- 239000013598 vector Substances 0.000 title claims description 77
- 238000000034 method Methods 0.000 title claims description 37
- 210000000964 retinal cone photoreceptor cell Anatomy 0.000 title claims description 32
- 108090000623 proteins and genes Proteins 0.000 claims description 46
- 108090000565 Capsid Proteins Proteins 0.000 claims description 40
- 102100023321 Ceruloplasmin Human genes 0.000 claims description 40
- 238000011282 treatment Methods 0.000 claims description 28
- 108091033409 CRISPR Proteins 0.000 claims description 26
- 208000017442 Retinal disease Diseases 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 18
- 108010042407 Endonucleases Proteins 0.000 claims description 17
- 108050001704 Opsin Proteins 0.000 claims description 17
- 102000010175 Opsin Human genes 0.000 claims description 17
- 108091030071 RNAI Proteins 0.000 claims description 17
- 230000009368 gene silencing by RNA Effects 0.000 claims description 17
- 208000006992 Color Vision Defects Diseases 0.000 claims description 16
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims description 15
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 14
- 102000004169 proteins and genes Human genes 0.000 claims description 12
- 108010003730 Cone Opsins Proteins 0.000 claims description 11
- 108020004459 Small interfering RNA Proteins 0.000 claims description 11
- 201000007254 color blindness Diseases 0.000 claims description 11
- 108091005462 Cation channels Proteins 0.000 claims description 10
- 101000597433 Mus musculus Nucleoredoxin-like protein 1 Proteins 0.000 claims description 10
- 238000010459 TALEN Methods 0.000 claims description 10
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 claims description 10
- 108010017070 Zinc Finger Nucleases Proteins 0.000 claims description 10
- 125000004122 cyclic group Chemical group 0.000 claims description 10
- 102100031780 Endonuclease Human genes 0.000 claims description 9
- 239000004055 small Interfering RNA Substances 0.000 claims description 9
- 238000010354 CRISPR gene editing Methods 0.000 claims description 8
- 102000004533 Endonucleases Human genes 0.000 claims description 8
- 108010025020 Nerve Growth Factor Proteins 0.000 claims description 8
- 102000007072 Nerve Growth Factors Human genes 0.000 claims description 8
- 102100036205 Nucleoredoxin-like protein 2 Human genes 0.000 claims description 8
- 101710106007 Nucleoredoxin-like protein 2 Proteins 0.000 claims description 8
- 108091027967 Small hairpin RNA Proteins 0.000 claims description 8
- 208000002780 macular degeneration Diseases 0.000 claims description 8
- 239000003900 neurotrophic factor Substances 0.000 claims description 8
- 101001104102 Homo sapiens X-linked retinitis pigmentosa GTPase regulator Proteins 0.000 claims description 7
- 101710163270 Nuclease Proteins 0.000 claims description 7
- 102100040092 X-linked retinitis pigmentosa GTPase regulator Human genes 0.000 claims description 7
- 230000002452 interceptive effect Effects 0.000 claims description 7
- 150000007523 nucleic acids Chemical group 0.000 claims description 7
- 102100029140 Cyclic nucleotide-gated cation channel beta-3 Human genes 0.000 claims description 6
- 101000771083 Homo sapiens Cyclic nucleotide-gated cation channel beta-3 Proteins 0.000 claims description 6
- 108091034117 Oligonucleotide Proteins 0.000 claims description 6
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 6
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 6
- 208000030533 eye disease Diseases 0.000 claims description 6
- NCYCYZXNIZJOKI-IOUUIBBYSA-N 11-cis-retinal Chemical compound O=C/C=C(\C)/C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-IOUUIBBYSA-N 0.000 claims description 5
- 208000036693 Color-vision disease Diseases 0.000 claims description 5
- 102100029142 Cyclic nucleotide-gated cation channel alpha-3 Human genes 0.000 claims description 5
- 102100039214 Guanine nucleotide-binding protein G(t) subunit alpha-2 Human genes 0.000 claims description 5
- 101000771071 Homo sapiens Cyclic nucleotide-gated cation channel alpha-3 Proteins 0.000 claims description 5
- 101000888142 Homo sapiens Guanine nucleotide-binding protein G(t) subunit alpha-2 Proteins 0.000 claims description 5
- 201000003533 Leber congenital amaurosis Diseases 0.000 claims description 5
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 5
- 102100040756 Rhodopsin Human genes 0.000 claims description 5
- 108090000820 Rhodopsin Proteins 0.000 claims description 5
- 238000009256 replacement therapy Methods 0.000 claims description 5
- 206010003694 Atrophy Diseases 0.000 claims description 4
- 201000001321 Bardet-Biedl syndrome Diseases 0.000 claims description 4
- 208000037663 Best vitelliform macular dystrophy Diseases 0.000 claims description 4
- 206010056715 Laurence-Moon-Bardet-Biedl syndrome Diseases 0.000 claims description 4
- 208000013657 Oligocone trichromacy Diseases 0.000 claims description 4
- 208000005587 Refsum Disease Diseases 0.000 claims description 4
- 208000027073 Stargardt disease Diseases 0.000 claims description 4
- 208000014769 Usher Syndromes Diseases 0.000 claims description 4
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 4
- 230000037444 atrophy Effects 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- 201000007790 vitelliform macular dystrophy Diseases 0.000 claims description 4
- 208000020938 vitelliform macular dystrophy 2 Diseases 0.000 claims description 4
- -1 RdCVFL or RdCVFL2 Proteins 0.000 claims description 2
- 239000002924 silencing RNA Substances 0.000 claims 1
- 230000014509 gene expression Effects 0.000 description 60
- 238000002347 injection Methods 0.000 description 51
- 239000007924 injection Substances 0.000 description 51
- 210000001525 retina Anatomy 0.000 description 38
- 210000004027 cell Anatomy 0.000 description 37
- 108090000765 processed proteins & peptides Proteins 0.000 description 37
- 230000002207 retinal effect Effects 0.000 description 36
- 210000001508 eye Anatomy 0.000 description 33
- 235000001014 amino acid Nutrition 0.000 description 25
- 241000282553 Macaca Species 0.000 description 24
- 229940024606 amino acid Drugs 0.000 description 24
- 150000001413 amino acids Chemical class 0.000 description 24
- 101710132601 Capsid protein Proteins 0.000 description 23
- 101710197658 Capsid protein VP1 Proteins 0.000 description 23
- 101710118046 RNA-directed RNA polymerase Proteins 0.000 description 23
- 101710108545 Viral protein 1 Proteins 0.000 description 23
- 239000002773 nucleotide Substances 0.000 description 17
- 125000003729 nucleotide group Chemical group 0.000 description 17
- 241001465754 Metazoa Species 0.000 description 16
- 101000785758 Mus musculus Arrestin-C Proteins 0.000 description 16
- 208000002352 blister Diseases 0.000 description 16
- 238000001476 gene delivery Methods 0.000 description 16
- 201000010099 disease Diseases 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- 238000010361 transduction Methods 0.000 description 15
- 230000026683 transduction Effects 0.000 description 15
- 210000002220 organoid Anatomy 0.000 description 14
- 230000006870 function Effects 0.000 description 13
- 230000035772 mutation Effects 0.000 description 13
- 102000040945 Transcription factor Human genes 0.000 description 12
- 108091023040 Transcription factor Proteins 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 238000012014 optical coherence tomography Methods 0.000 description 12
- 235000018102 proteins Nutrition 0.000 description 12
- 230000001225 therapeutic effect Effects 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 238000003780 insertion Methods 0.000 description 11
- 230000037431 insertion Effects 0.000 description 11
- 239000013607 AAV vector Substances 0.000 description 9
- 241000288906 Primates Species 0.000 description 9
- 238000013459 approach Methods 0.000 description 9
- 238000001415 gene therapy Methods 0.000 description 9
- 108091008695 photoreceptors Proteins 0.000 description 9
- 239000002245 particle Substances 0.000 description 8
- 108020005004 Guide RNA Proteins 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000012423 maintenance Methods 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 230000002093 peripheral effect Effects 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- 230000000638 stimulation Effects 0.000 description 7
- 238000011269 treatment regimen Methods 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 101000785755 Homo sapiens Arrestin-C Proteins 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 108700019146 Transgenes Proteins 0.000 description 6
- 230000000295 complement effect Effects 0.000 description 6
- 239000012530 fluid Substances 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 230000008685 targeting Effects 0.000 description 6
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 5
- 108700028369 Alleles Proteins 0.000 description 5
- 108050003620 Arrestin-C Proteins 0.000 description 5
- 102100026440 Arrestin-C Human genes 0.000 description 5
- 241000702421 Dependoparvovirus Species 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 210000000234 capsid Anatomy 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 230000002102 hyperpolarization Effects 0.000 description 5
- 238000003384 imaging method Methods 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 230000004298 light response Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- 208000002267 Anti-neutrophil cytoplasmic antibody-associated vasculitis Diseases 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 4
- 102100029362 Cone-rod homeobox protein Human genes 0.000 description 4
- 108020004414 DNA Proteins 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 230000000763 evoking effect Effects 0.000 description 4
- 230000004438 eyesight Effects 0.000 description 4
- 238000003197 gene knockdown Methods 0.000 description 4
- 230000028993 immune response Effects 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 230000003472 neutralizing effect Effects 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 239000013603 viral vector Substances 0.000 description 4
- 210000002845 virion Anatomy 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 3
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101000919370 Homo sapiens Cone-rod homeobox protein Proteins 0.000 description 3
- 206010025421 Macule Diseases 0.000 description 3
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 201000007737 Retinal degeneration Diseases 0.000 description 3
- 206010038848 Retinal detachment Diseases 0.000 description 3
- 102100035178 Retinoic acid receptor RXR-alpha Human genes 0.000 description 3
- 102100023606 Retinoic acid receptor alpha Human genes 0.000 description 3
- 108010066463 Retinoid X Receptor alpha Proteins 0.000 description 3
- 241000193996 Streptococcus pyogenes Species 0.000 description 3
- 102100033451 Thyroid hormone receptor beta Human genes 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 230000034431 double-strand break repair via homologous recombination Effects 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 108010074774 long-wavelength opsin Proteins 0.000 description 3
- 230000028161 membrane depolarization Effects 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 102000006255 nuclear receptors Human genes 0.000 description 3
- 108020004017 nuclear receptors Proteins 0.000 description 3
- 210000000608 photoreceptor cell Anatomy 0.000 description 3
- 230000004258 retinal degeneration Effects 0.000 description 3
- 230000004264 retinal detachment Effects 0.000 description 3
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 3
- 108091008726 retinoic acid receptors α Proteins 0.000 description 3
- 125000006850 spacer group Chemical group 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 108091008762 thyroid hormone receptors ß Proteins 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 2
- 108091010877 Allograft inflammatory factor 1 Proteins 0.000 description 2
- 102100040121 Allograft inflammatory factor 1 Human genes 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 101710134031 CCAAT/enhancer-binding protein beta Proteins 0.000 description 2
- 102100034798 CCAAT/enhancer-binding protein beta Human genes 0.000 description 2
- 208000003098 Ganglion Cysts Diseases 0.000 description 2
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 2
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 108010050754 Halorhodopsins Proteins 0.000 description 2
- 101000597428 Homo sapiens Nucleoredoxin-like protein 1 Proteins 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- 102100035399 Nucleoredoxin-like protein 1 Human genes 0.000 description 2
- 101710172711 Structural protein Proteins 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 2
- 208000005400 Synovial Cyst Diseases 0.000 description 2
- 108700009124 Transcription Initiation Site Proteins 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 101150063416 add gene Proteins 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 230000004456 color vision Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 210000000744 eyelid Anatomy 0.000 description 2
- 238000002073 fluorescence micrograph Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- 230000004371 high visual acuity Effects 0.000 description 2
- 238000010562 histological examination Methods 0.000 description 2
- 238000002991 immunohistochemical analysis Methods 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- NBQNWMBBSKPBAY-UHFFFAOYSA-N iodixanol Chemical compound IC=1C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C(I)C=1N(C(=O)C)CC(O)CN(C(C)=O)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NBQNWMBBSKPBAY-UHFFFAOYSA-N 0.000 description 2
- 229960004359 iodixanol Drugs 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 201000005111 ocular hyperemia Diseases 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 210000001747 pupil Anatomy 0.000 description 2
- 230000007420 reactivation Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000036390 resting membrane potential Effects 0.000 description 2
- 210000000880 retinal rod photoreceptor cell Anatomy 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000004304 visual acuity Effects 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 238000011179 visual inspection Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-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
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 1
- 241000202702 Adeno-associated virus - 3 Species 0.000 description 1
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 1
- 241001164823 Adeno-associated virus - 7 Species 0.000 description 1
- 241001164825 Adeno-associated virus - 8 Species 0.000 description 1
- 239000012103 Alexa Fluor 488 Substances 0.000 description 1
- 239000012110 Alexa Fluor 594 Substances 0.000 description 1
- 239000012114 Alexa Fluor 647 Substances 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 238000012935 Averaging Methods 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108010035848 Channelrhodopsins Proteins 0.000 description 1
- 101710175910 Cone-rod homeobox protein Proteins 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 102220605874 Cytosolic arginine sensor for mTORC1 subunit 2_D10A_mutation Human genes 0.000 description 1
- DWJXYEABWRJFSP-XOBRGWDASA-N DAPT Chemical compound N([C@@H](C)C(=O)N[C@H](C(=O)OC(C)(C)C)C=1C=CC=CC=1)C(=O)CC1=CC(F)=CC(F)=C1 DWJXYEABWRJFSP-XOBRGWDASA-N 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 101150066002 GFP gene Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102100038073 General transcription factor II-I Human genes 0.000 description 1
- 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 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101001032427 Homo sapiens General transcription factor II-I Proteins 0.000 description 1
- 101100038211 Homo sapiens RPGR gene Proteins 0.000 description 1
- 208000032578 Inherited retinal disease Diseases 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
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 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
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 1
- 102000010904 Mediator Complex Subunit 1 Human genes 0.000 description 1
- 108010062495 Mediator Complex Subunit 1 Proteins 0.000 description 1
- 101100324474 Mus musculus Arr3 gene Proteins 0.000 description 1
- 101000903581 Natronomonas pharaonis Halorhodopsin Proteins 0.000 description 1
- 208000012266 Needlestick injury Diseases 0.000 description 1
- 108020003217 Nuclear RNA Proteins 0.000 description 1
- 102000043141 Nuclear RNA Human genes 0.000 description 1
- 101150114678 OPN1MW gene Proteins 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 206010034972 Photosensitivity reaction Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 101150116978 RPE65 gene Proteins 0.000 description 1
- 108010034634 Repressor Proteins Proteins 0.000 description 1
- 208000002367 Retinal Perforations Diseases 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 101100166144 Staphylococcus aureus cas9 gene Proteins 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 108700026226 TATA Box Proteins 0.000 description 1
- 102000006612 Transducin Human genes 0.000 description 1
- 108010087042 Transducin Proteins 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 108091006088 activator proteins Proteins 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000033289 adaptive immune response Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 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 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 238000007622 bioinformatic analysis Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- BMLSTPRTEKLIPM-UHFFFAOYSA-I calcium;potassium;disodium;hydrogen carbonate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].OC([O-])=O BMLSTPRTEKLIPM-UHFFFAOYSA-I 0.000 description 1
- ZEWYCNBZMPELPF-UHFFFAOYSA-J calcium;potassium;sodium;2-hydroxypropanoic acid;sodium;tetrachloride Chemical compound [Na].[Na+].[Cl-].[Cl-].[Cl-].[Cl-].[K+].[Ca+2].CC(O)C(O)=O ZEWYCNBZMPELPF-UHFFFAOYSA-J 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000005782 double-strand break Effects 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000011977 dual antiplatelet therapy Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 210000003953 foreskin Anatomy 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 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
- 229940050410 gluconate Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000013388 immunohistochemistry analysis Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000012405 in silico analysis Methods 0.000 description 1
- 238000000126 in silico method Methods 0.000 description 1
- 238000011503 in vivo imaging Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 208000029233 macular holes Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 108010054609 middle-wavelength opsin Proteins 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000012120 mounting media Substances 0.000 description 1
- 108700012622 mouse arrestin 4 Proteins 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000036211 photosensitivity Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 210000000977 primary visual cortex Anatomy 0.000 description 1
- 238000011809 primate model Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 229960004134 propofol Drugs 0.000 description 1
- OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical compound CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 description 1
- 230000010344 pupil dilation Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 210000002763 pyramidal cell Anatomy 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004251 retinal disorganization Effects 0.000 description 1
- 230000004243 retinal function Effects 0.000 description 1
- 239000000790 retinal pigment Substances 0.000 description 1
- 210000000844 retinal pigment epithelial cell Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000011808 rodent model Methods 0.000 description 1
- 238000009781 safety test method Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000000405 serological effect Effects 0.000 description 1
- 230000005783 single-strand break Effects 0.000 description 1
- 101150039622 so gene Proteins 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000008093 supporting effect Effects 0.000 description 1
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000012731 temporal analysis Methods 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229940125379 topical corticosteroid Drugs 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 108091006108 transcriptional coactivators Proteins 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000011222 transcriptome analysis Methods 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 230000001228 trophic effect Effects 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 230000016776 visual perception Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 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
- A61K48/005—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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/125—Picornaviridae, e.g. calicivirus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/0075—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the delivery route, e.g. oral, subcutaneous
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Virology (AREA)
- Biochemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Plant Pathology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Ophthalmology & Optometry (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Mycology (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 |
|---|---|---|---|
| EP17306430 | 2017-10-20 | ||
| EP17306430.4 | 2017-10-20 | ||
| PCT/EP2018/078856 WO2019077159A1 (en) | 2017-10-20 | 2018-10-22 | METHODS OF EXPRESSING POLYNUCLEOTIDE OF INTEREST IN CONE PHOTORECCEPTORS OF A SUBJECT COMPRISING SUB-RETINAL ADMINISTRATION OF A THERAPEUTICALLY EFFECTIVE AMOUNT OF A RECOMBINANT AAV9 DERIVATIVE VECTOR |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2021500030A JP2021500030A (ja) | 2021-01-07 |
| JP2021500030A5 JP2021500030A5 (enExample) | 2021-11-25 |
| JP7420710B2 true JP7420710B2 (ja) | 2024-01-23 |
Family
ID=60201476
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020522014A Active JP7420710B2 (ja) | 2017-10-20 | 2018-10-22 | 組換えaav9由来ベクターの治療有効量の網膜下送達を含む、対象の錐体視細胞において目的のポリヌクレオチドを発現させる方法 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US11723988B2 (enExample) |
| EP (1) | EP3697448A1 (enExample) |
| JP (1) | JP7420710B2 (enExample) |
| KR (1) | KR102763312B1 (enExample) |
| CN (1) | CN111867635A (enExample) |
| WO (1) | WO2019077159A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2027889A1 (en) * | 2007-06-05 | 2009-02-25 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | New neuronal viability factor and use thereof |
| WO2018187552A1 (en) | 2017-04-05 | 2018-10-11 | University Of Massachusetts | Minigene therapy |
| US12390539B2 (en) | 2019-05-20 | 2025-08-19 | University Of Massachusetts | Minigene therapy |
| WO2021204407A1 (en) * | 2020-04-10 | 2021-10-14 | Sorbonne Université | G-protein-gated-k+ channel-mediated enhancements in light sensitivity in rod-cone dystrophy (rcd) |
| CN113121655B (zh) * | 2021-04-19 | 2021-11-19 | 上海信致医药科技有限公司 | 眼部和肌肉特异靶向型腺相关病毒载体及其应用 |
| EP4326339B1 (en) | 2021-04-20 | 2025-04-02 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Compositions and methods for treating retinal degenerative disorders |
| JP2024520558A (ja) * | 2021-05-26 | 2024-05-24 | スパーリングヴィジョン | Gタンパク質ゲート-k+チャネルを介した桿体-錐体ジストロフィー(rcd)における光感受性の増強 |
| CN120303405A (zh) | 2022-10-20 | 2025-07-11 | 节约视觉公司 | 用于治疗视网膜退行性疾病的组合物和方法 |
| WO2024110770A1 (en) * | 2022-11-22 | 2024-05-30 | INSERM (Institut National de la Santé et de la Recherche Médicale) | A new promoter for retinal pigment epithelium (rpe) targeted gene therapy |
| WO2024182558A1 (en) * | 2023-02-28 | 2024-09-06 | The Saban Research Institute; Children's Hospital Los Angeles | Fluorescent cone reporter ips cells, retinal organoids and uses thereof |
| CN117247434B (zh) * | 2023-11-10 | 2024-02-02 | 上海朗昇生物科技有限公司 | 衣壳修饰型病毒载体及其制备和用途 |
| CN119350454B (zh) * | 2024-12-27 | 2025-03-25 | 上海朗昇生物科技有限公司 | 衣壳重排型腺相关病毒载体及其用途 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014518614A (ja) | 2011-04-22 | 2014-08-07 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 変異体キャプシドを有するアデノ関連ウイルスビリオンおよびその使用方法 |
| WO2016141078A1 (en) | 2015-03-02 | 2016-09-09 | Avalanche Biotechnologies, Inc. | Compositions and methods for intravitreal delivery of polynucleotides to retinal cones |
| JP2017510296A (ja) | 2014-03-17 | 2017-04-13 | アドヴェラム バイオテクノロジーズ, インコーポレイテッド | 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 Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2265460A1 (en) | 1996-09-11 | 1998-03-19 | The Government Of The United States Of America, Represented By The Secre Tary, Department Of Health And Human Services | Aav4 vector and uses thereof |
| US6156303A (en) | 1997-06-11 | 2000-12-05 | University Of Washington | Adeno-associated virus (AAV) isolates and AAV vectors derived therefrom |
| EP1082413B1 (en) | 1998-05-28 | 2008-07-23 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | Aav5 vector and uses thereof |
| AU768729B2 (en) | 1998-11-05 | 2004-01-08 | Trustees Of The University Of Pennsylvania, The | Adeno-associated virus serotype 1 nucleic acid sequences, vectors and host cells containing same |
| DE10216005A1 (de) | 2002-04-11 | 2003-10-30 | Max Planck Gesellschaft | Verwendung von biologischen Photorezeptoren als direkt lichtgesteuerte Ionenkanäle |
| ES2874298T3 (es) | 2003-09-30 | 2021-11-04 | Univ Pennsylvania | Clados de virus adenoasociados (AAV), secuencias, vectores que contienen el mismo, y usos de los mismos |
| EP2465925A1 (en) | 2005-07-22 | 2012-06-20 | The Board Of Trustees Of The Leland | Light-activated cation channel and uses thereof |
| EP3437473A1 (en) | 2006-05-04 | 2019-02-06 | Wayne State University | Restoration of visual responses by in vivo delivery of rhodopsin nucleic acids |
| EP2027889A1 (en) | 2007-06-05 | 2009-02-25 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | New neuronal viability factor and use thereof |
| US10266845B2 (en) * | 2013-02-08 | 2019-04-23 | The Trustees Of The University Of Pennsylvania | Enhanced AAV-mediated gene transfer for retinal therapies |
| KR20250068794A (ko) * | 2013-12-12 | 2025-05-16 | 더 브로드 인스티튜트, 인코퍼레이티드 | 게놈 편집을 위한 crispr-cas 시스템 및 조성물의 전달, 용도 및 치료적 응용 |
| US10308957B2 (en) * | 2014-03-04 | 2019-06-04 | University Of Florida Research Foundation, Inc. | rAAV vectors and methods for transduction of photoreceptors and RPE cells |
| AU2015252797C1 (en) | 2014-05-02 | 2021-04-22 | Genzyme Corporation | AAV vectors for retinal and CNS gene therapy |
| HRP20241154T1 (hr) | 2014-07-24 | 2024-11-22 | Massachusetts Eye & Ear Infirmary | Rpgr genska terapija za pigmentnu retinopatiju |
| EP4209501A1 (en) * | 2016-05-13 | 2023-07-12 | 4D Molecular Therapeutics Inc. | Adeno-associated virus variant capsids and methods of use thereof |
| CA3114549A1 (en) | 2017-02-21 | 2018-08-30 | University Of Florida Research Foundation, Incorporated | Modified aav capsid proteins and uses thereof |
| CA3078277A1 (en) * | 2017-10-16 | 2019-04-25 | Vigeneron Gmbh | Aav vectors |
-
2018
- 2018-10-22 US US16/756,988 patent/US11723988B2/en active Active
- 2018-10-22 EP EP18789421.7A patent/EP3697448A1/en active Pending
- 2018-10-22 KR KR1020207014057A patent/KR102763312B1/ko active Active
- 2018-10-22 WO PCT/EP2018/078856 patent/WO2019077159A1/en not_active Ceased
- 2018-10-22 CN CN201880081245.8A patent/CN111867635A/zh active Pending
- 2018-10-22 JP JP2020522014A patent/JP7420710B2/ja active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2014518614A (ja) | 2011-04-22 | 2014-08-07 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 変異体キャプシドを有するアデノ関連ウイルスビリオンおよびその使用方法 |
| JP2017510296A (ja) | 2014-03-17 | 2017-04-13 | アドヴェラム バイオテクノロジーズ, インコーポレイテッド | 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 |
| WO2016141078A1 (en) | 2015-03-02 | 2016-09-09 | Avalanche Biotechnologies, Inc. | Compositions and methods for intravitreal delivery of polynucleotides to retinal cones |
Non-Patent Citations (1)
| Title |
|---|
| Investigative Ophthalmology and Visual Science, 2015, Vol. 56, No.7, pp. 2066,STN[ONLINE],[retrieved on 2022.09.20], Accession No. 0052551616 |
Also Published As
| Publication number | Publication date |
|---|---|
| KR102763312B1 (ko) | 2025-02-07 |
| JP2021500030A (ja) | 2021-01-07 |
| US20210268125A1 (en) | 2021-09-02 |
| KR20200103634A (ko) | 2020-09-02 |
| EP3697448A1 (en) | 2020-08-26 |
| CN111867635A (zh) | 2020-10-30 |
| US11723988B2 (en) | 2023-08-15 |
| WO2019077159A1 (en) | 2019-04-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7420710B2 (ja) | 組換えaav9由来ベクターの治療有効量の網膜下送達を含む、対象の錐体視細胞において目的のポリヌクレオチドを発現させる方法 | |
| TWI775096B (zh) | 使用腺相關病毒(aav)sflt-1治療老年性黃斑部退化(amd) | |
| EP3570895A1 (en) | Methods of expressing a polynucleotide of interest in the cone photoreceptors | |
| US20250290096A1 (en) | Gene therapy to improve vision | |
| CN118480544A (zh) | 用于治疗显性视网膜色素变性的组合物和方法 | |
| JP2023512473A (ja) | 網膜神経節細胞の再生 | |
| EP4389894A2 (en) | Riboswitch modulated gene therapy for retinal diseases | |
| BR112019017327A2 (pt) | terapia gênica para distúrbios oculares | |
| CN113795279B (zh) | 靶向akt通路的神经保护性基因疗法 | |
| US11541072B2 (en) | AAV-CRISPR/Cas9 genome editing of VEGFR2 for treating ocular diseases | |
| US11866480B2 (en) | Vector-mediated immune tolerance in the eye | |
| US20240124893A1 (en) | Methods of Treating Human X-Linked Retinoschisis Using Gene Therapy | |
| Cai et al. | An engineered intravitreal injection RPE-tropic AAV vector expressing a bispecific antibody binding VEGF-A and ANG-2 rescues nAMD in animal models and patients | |
| Matsuki | Development of gene therapy for achromatopsia due to CNGA3 mutations | |
| HK1248595B (en) | Gene therapy to improve vision |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211015 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20211015 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20221003 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20221222 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230403 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20230612 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230928 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20231002 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20231020 |
|
| 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: 20231218 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20240111 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 7420710 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |