KR102686857B1 - 변이체 RNAi - Google Patents
변이체 RNAi Download PDFInfo
- Publication number
- KR102686857B1 KR102686857B1 KR1020207011227A KR20207011227A KR102686857B1 KR 102686857 B1 KR102686857 B1 KR 102686857B1 KR 1020207011227 A KR1020207011227 A KR 1020207011227A KR 20207011227 A KR20207011227 A KR 20207011227A KR 102686857 B1 KR102686857 B1 KR 102686857B1
- Authority
- KR
- South Korea
- Prior art keywords
- delete delete
- vector
- aav
- nucleic acid
- promoter
- 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
- 230000009368 gene silencing by RNA Effects 0.000 title claims abstract description 222
- 108091030071 RNAI Proteins 0.000 title claims abstract 23
- 239000002245 particle Substances 0.000 claims abstract description 308
- 239000013598 vector Substances 0.000 claims abstract description 234
- 230000003612 virological effect Effects 0.000 claims abstract description 153
- 208000023105 Huntington disease Diseases 0.000 claims abstract description 104
- 241000701161 unidentified adenovirus Species 0.000 claims abstract description 97
- 230000014509 gene expression Effects 0.000 claims abstract description 81
- 239000013608 rAAV vector Substances 0.000 claims abstract description 55
- 150000007523 nucleic acids Chemical group 0.000 claims description 284
- 241000702421 Dependoparvovirus Species 0.000 claims description 232
- 102000039446 nucleic acids Human genes 0.000 claims description 191
- 108020004707 nucleic acids Proteins 0.000 claims description 191
- 241000702423 Adeno-associated virus - 2 Species 0.000 claims description 139
- 108700011259 MicroRNAs Proteins 0.000 claims description 104
- 239000002679 microRNA Substances 0.000 claims description 103
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 85
- 210000000234 capsid Anatomy 0.000 claims description 76
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 74
- 241000700584 Simplexvirus Species 0.000 claims description 68
- 239000002773 nucleotide Substances 0.000 claims description 50
- 125000003729 nucleotide group Chemical group 0.000 claims description 50
- 241000700605 Viruses Species 0.000 claims description 49
- 241000124008 Mammalia Species 0.000 claims description 46
- 230000000295 complement effect Effects 0.000 claims description 46
- 239000000203 mixture Substances 0.000 claims description 41
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 claims description 37
- 230000008488 polyadenylation Effects 0.000 claims description 37
- 230000002401 inhibitory effect Effects 0.000 claims description 30
- 241000701022 Cytomegalovirus Species 0.000 claims description 27
- 241001655883 Adeno-associated virus - 1 Species 0.000 claims description 26
- 241000712899 Lymphocytic choriomeningitis mammarenavirus Species 0.000 claims description 22
- 241000283690 Bos taurus Species 0.000 claims description 21
- 241000711975 Vesicular stomatitis virus Species 0.000 claims description 18
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 18
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 18
- 108010006025 bovine growth hormone Proteins 0.000 claims description 17
- 229920001184 polypeptide Polymers 0.000 claims description 17
- 238000003776 cleavage reaction Methods 0.000 claims description 16
- 230000007017 scission Effects 0.000 claims description 16
- 241001634120 Adeno-associated virus - 5 Species 0.000 claims description 15
- 108091027967 Small hairpin RNA Proteins 0.000 claims description 15
- 241000972680 Adeno-associated virus - 6 Species 0.000 claims description 14
- 241000714474 Rous sarcoma virus Species 0.000 claims description 14
- 241000202702 Adeno-associated virus - 3 Species 0.000 claims description 13
- 241000580270 Adeno-associated virus - 4 Species 0.000 claims description 13
- 241001164823 Adeno-associated virus - 7 Species 0.000 claims description 13
- 241001164825 Adeno-associated virus - 8 Species 0.000 claims description 13
- 241000649046 Adeno-associated virus 11 Species 0.000 claims description 13
- 241000649047 Adeno-associated virus 12 Species 0.000 claims description 13
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 claims description 13
- 241000649045 Adeno-associated virus 10 Species 0.000 claims description 12
- 241000283707 Capra Species 0.000 claims description 12
- 239000003623 enhancer Substances 0.000 claims description 12
- 230000035772 mutation Effects 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 11
- 239000004055 small Interfering RNA Substances 0.000 claims description 11
- 230000037430 deletion Effects 0.000 claims description 10
- 238000012217 deletion Methods 0.000 claims description 10
- 230000008685 targeting Effects 0.000 claims description 10
- 241000282465 Canis Species 0.000 claims description 9
- 241001115402 Ebolavirus Species 0.000 claims description 9
- 206010066919 Epidemic polyarthritis Diseases 0.000 claims description 9
- 241000713666 Lentivirus Species 0.000 claims description 9
- 241001115401 Marburgvirus Species 0.000 claims description 9
- 241001494479 Pecora Species 0.000 claims description 9
- 102100028251 Phosphoglycerate kinase 1 Human genes 0.000 claims description 9
- 101710139464 Phosphoglycerate kinase 1 Proteins 0.000 claims description 9
- 241000711798 Rabies lyssavirus Species 0.000 claims description 9
- 241000710942 Ross River virus Species 0.000 claims description 9
- 230000001697 htt accumulation Effects 0.000 claims description 8
- 239000004098 Tetracycline Substances 0.000 claims description 7
- 229960002180 tetracycline Drugs 0.000 claims description 7
- 229930101283 tetracycline Natural products 0.000 claims description 7
- 235000019364 tetracycline Nutrition 0.000 claims description 7
- 150000003522 tetracyclines Chemical class 0.000 claims description 7
- 108091005904 Hemoglobin subunit beta Proteins 0.000 claims description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 6
- 210000004185 liver Anatomy 0.000 claims description 6
- 102100021519 Hemoglobin subunit beta Human genes 0.000 claims description 5
- 101000933465 Homo sapiens Beta-glucuronidase Proteins 0.000 claims description 5
- 241000713869 Moloney murine leukemia virus Species 0.000 claims description 5
- 239000013646 rAAV2 vector Substances 0.000 claims description 5
- 238000011144 upstream manufacturing Methods 0.000 claims description 5
- 102000010292 Peptide Elongation Factor 1 Human genes 0.000 claims description 4
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 claims description 4
- 108010071690 Prealbumin Proteins 0.000 claims description 4
- 108010017842 Telomerase Proteins 0.000 claims description 4
- 102000009190 Transthyretin Human genes 0.000 claims description 4
- 239000013604 expression vector Substances 0.000 claims description 4
- 108010022394 Threonine synthase Proteins 0.000 claims description 3
- 102000004419 dihydrofolate reductase Human genes 0.000 claims description 3
- 230000001177 retroviral effect Effects 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 60
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 28
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 199
- 210000004027 cell Anatomy 0.000 description 111
- 108090000623 proteins and genes Proteins 0.000 description 101
- 241000699670 Mus sp. Species 0.000 description 50
- 102000040430 polynucleotide Human genes 0.000 description 44
- 108091033319 polynucleotide Proteins 0.000 description 44
- 239000002157 polynucleotide Substances 0.000 description 44
- 108020004999 messenger RNA Proteins 0.000 description 39
- 210000004556 brain Anatomy 0.000 description 38
- 102000004169 proteins and genes Human genes 0.000 description 37
- 230000006870 function Effects 0.000 description 30
- 108090000565 Capsid Proteins Proteins 0.000 description 28
- 102100023321 Ceruloplasmin Human genes 0.000 description 28
- 108020004414 DNA Proteins 0.000 description 28
- 210000002569 neuron Anatomy 0.000 description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 24
- 238000004806 packaging method and process Methods 0.000 description 24
- 208000024891 symptom Diseases 0.000 description 23
- 210000001519 tissue Anatomy 0.000 description 23
- 238000011282 treatment Methods 0.000 description 23
- 238000004519 manufacturing process Methods 0.000 description 21
- 239000013603 viral vector Substances 0.000 description 21
- 230000030279 gene silencing Effects 0.000 description 19
- 201000010099 disease Diseases 0.000 description 18
- 208000015181 infectious disease Diseases 0.000 description 17
- 239000013612 plasmid Substances 0.000 description 17
- 230000000694 effects Effects 0.000 description 16
- 238000002347 injection Methods 0.000 description 16
- 239000007924 injection Substances 0.000 description 16
- 230000010076 replication Effects 0.000 description 16
- 108700019146 Transgenes Proteins 0.000 description 15
- 238000010367 cloning Methods 0.000 description 15
- 210000003169 central nervous system Anatomy 0.000 description 14
- 230000002458 infectious effect Effects 0.000 description 14
- 210000001577 neostriatum Anatomy 0.000 description 13
- 238000010361 transduction Methods 0.000 description 13
- 230000026683 transduction Effects 0.000 description 13
- 241000699666 Mus <mouse, genus> Species 0.000 description 12
- 230000037396 body weight Effects 0.000 description 12
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 11
- 125000003275 alpha amino acid group Chemical group 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- 238000013459 approach Methods 0.000 description 9
- 238000011156 evaluation Methods 0.000 description 9
- 230000001105 regulatory effect Effects 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- 125000000539 amino acid group Chemical group 0.000 description 8
- 210000001159 caudate nucleus Anatomy 0.000 description 8
- 230000006735 deficit Effects 0.000 description 8
- 238000012226 gene silencing method Methods 0.000 description 8
- 230000001939 inductive effect Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 210000002637 putamen Anatomy 0.000 description 8
- 230000009182 swimming Effects 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 238000001890 transfection Methods 0.000 description 8
- 239000013607 AAV vector Substances 0.000 description 7
- 101001030698 Mus musculus Huntingtin Proteins 0.000 description 7
- 238000000540 analysis of variance Methods 0.000 description 7
- 230000000692 anti-sense effect Effects 0.000 description 7
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 238000013518 transcription Methods 0.000 description 7
- 230000035897 transcription Effects 0.000 description 7
- 102000053602 DNA Human genes 0.000 description 6
- 101001030705 Homo sapiens Huntingtin Proteins 0.000 description 6
- 101150043003 Htt gene Proteins 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 230000000593 degrading effect Effects 0.000 description 6
- 208000035475 disorder Diseases 0.000 description 6
- 238000010172 mouse model Methods 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 230000000750 progressive effect Effects 0.000 description 6
- 230000002441 reversible effect Effects 0.000 description 6
- 108020005345 3' Untranslated Regions Proteins 0.000 description 5
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 5
- 230000003542 behavioural effect Effects 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- 210000004958 brain cell Anatomy 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 210000004498 neuroglial cell Anatomy 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 4
- 108091032955 Bacterial small RNA Proteins 0.000 description 4
- 206010008748 Chorea Diseases 0.000 description 4
- 241000713813 Gibbon ape leukemia virus Species 0.000 description 4
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 4
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 4
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 4
- 241000238631 Hexapoda Species 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000823116 Homo sapiens Alpha-1-antitrypsin Proteins 0.000 description 4
- 108091092195 Intron Proteins 0.000 description 4
- 108090000157 Metallothionein Proteins 0.000 description 4
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 4
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 4
- 241000288906 Primates Species 0.000 description 4
- 238000011529 RT qPCR Methods 0.000 description 4
- 241000713325 Visna/maedi virus Species 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 238000009825 accumulation Methods 0.000 description 4
- 239000000074 antisense oligonucleotide Substances 0.000 description 4
- 238000012230 antisense oligonucleotides Methods 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000009286 beneficial effect Effects 0.000 description 4
- 210000000349 chromosome Anatomy 0.000 description 4
- 230000001687 destabilization Effects 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 239000005090 green fluorescent protein Substances 0.000 description 4
- 102000054185 human HTT Human genes 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000001404 mediated effect Effects 0.000 description 4
- 108091070501 miRNA Proteins 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 108010040003 polyglutamine Proteins 0.000 description 4
- 229920000155 polyglutamine Polymers 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 101150066583 rep gene Proteins 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 238000013519 translation Methods 0.000 description 4
- 241000701447 unidentified baculovirus Species 0.000 description 4
- DIGQNXIGRZPYDK-WKSCXVIASA-N (2R)-6-amino-2-[[2-[[(2S)-2-[[2-[[(2R)-2-[[(2S)-2-[[(2R,3S)-2-[[2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S,3S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2R)-2-[[2-[[2-[[2-[(2-amino-1-hydroxyethylidene)amino]-3-carboxy-1-hydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxypropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1,5-dihydroxy-5-iminopentylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxybutylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1,3-dihydroxypropylidene]amino]-1-hydroxyethylidene]amino]-1-hydroxy-3-sulfanylpropylidene]amino]-1-hydroxyethylidene]amino]hexanoic acid Chemical compound C[C@@H]([C@@H](C(=N[C@@H](CS)C(=N[C@@H](C)C(=N[C@@H](CO)C(=NCC(=N[C@@H](CCC(=N)O)C(=NC(CS)C(=N[C@H]([C@H](C)O)C(=N[C@H](CS)C(=N[C@H](CO)C(=NCC(=N[C@H](CS)C(=NCC(=N[C@H](CCCCN)C(=O)O)O)O)O)O)O)O)O)O)O)O)O)O)O)N=C([C@H](CS)N=C([C@H](CO)N=C([C@H](CO)N=C([C@H](C)N=C(CN=C([C@H](CO)N=C([C@H](CS)N=C(CN=C(C(CS)N=C(C(CC(=O)O)N=C(CN)O)O)O)O)O)O)O)O)O)O)O)O DIGQNXIGRZPYDK-WKSCXVIASA-N 0.000 description 3
- 206010012289 Dementia Diseases 0.000 description 3
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 3
- 108050004784 Huntingtin Proteins 0.000 description 3
- 102000016252 Huntingtin Human genes 0.000 description 3
- 241000713326 Jaagsiekte sheep retrovirus Species 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- 102000003792 Metallothionein Human genes 0.000 description 3
- 108091033773 MiR-155 Proteins 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 3
- 230000003042 antagnostic effect Effects 0.000 description 3
- 210000004507 artificial chromosome Anatomy 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 208000012601 choreatic disease Diseases 0.000 description 3
- 239000000356 contaminant Substances 0.000 description 3
- 230000001054 cortical effect Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 238000001415 gene therapy Methods 0.000 description 3
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000002452 interceptive effect Effects 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000002502 liposome Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 210000000274 microglia Anatomy 0.000 description 3
- 230000004973 motor coordination Effects 0.000 description 3
- 230000007659 motor function Effects 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 230000016273 neuron death Effects 0.000 description 3
- 108091007428 primary miRNA Proteins 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 238000009987 spinning Methods 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- 230000009752 translational inhibition Effects 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 108700028369 Alleles Proteins 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241001203868 Autographa californica Species 0.000 description 2
- 241000271566 Aves Species 0.000 description 2
- 241000714230 Avian leukemia virus Species 0.000 description 2
- 241000713704 Bovine immunodeficiency virus Species 0.000 description 2
- 101150044789 Cap gene Proteins 0.000 description 2
- 241000713756 Caprine arthritis encephalitis virus Species 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 108091033380 Coding strand Proteins 0.000 description 2
- 101710177611 DNA polymerase II large subunit Proteins 0.000 description 2
- 101710184669 DNA polymerase II small subunit Proteins 0.000 description 2
- 206010061818 Disease progression Diseases 0.000 description 2
- 201000011001 Ebola Hemorrhagic Fever Diseases 0.000 description 2
- UPEZCKBFRMILAV-JNEQICEOSA-N Ecdysone Natural products O=C1[C@H]2[C@@](C)([C@@H]3C([C@@]4(O)[C@@](C)([C@H]([C@H]([C@@H](O)CCC(O)(C)C)C)CC4)CC3)=C1)C[C@H](O)[C@H](O)C2 UPEZCKBFRMILAV-JNEQICEOSA-N 0.000 description 2
- 101000633737 Echis carinatus sochureki Snaclec 3 Proteins 0.000 description 2
- 241000713730 Equine infectious anemia virus Species 0.000 description 2
- 241000713800 Feline immunodeficiency virus Species 0.000 description 2
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 2
- 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 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 241000711549 Hepacivirus C Species 0.000 description 2
- 101001067833 Homo sapiens Peptidyl-prolyl cis-trans isomerase A Proteins 0.000 description 2
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 2
- 241001135569 Human adenovirus 5 Species 0.000 description 2
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 2
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 2
- 241001505307 Jembrana disease virus Species 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 241001480512 Mammalian orthoreovirus 3 Species 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 238000000636 Northern blotting Methods 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 101710149951 Protein Tat Proteins 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- 238000003559 RNA-seq method Methods 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 241000710961 Semliki Forest virus Species 0.000 description 2
- 241000713311 Simian immunodeficiency virus Species 0.000 description 2
- 241000701093 Suid alphaherpesvirus 1 Species 0.000 description 2
- 102100036049 T-complex protein 1 subunit gamma Human genes 0.000 description 2
- 108700005077 Viral Genes Proteins 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 230000016571 aggressive behavior Effects 0.000 description 2
- UPEZCKBFRMILAV-UHFFFAOYSA-N alpha-Ecdysone Natural products C1C(O)C(O)CC2(C)C(CCC3(C(C(C(O)CCC(C)(C)O)C)CCC33O)C)C3=CC(=O)C21 UPEZCKBFRMILAV-UHFFFAOYSA-N 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 230000036506 anxiety Effects 0.000 description 2
- 210000001130 astrocyte Anatomy 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 238000012742 biochemical analysis Methods 0.000 description 2
- 208000006752 brain edema Diseases 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 101150062912 cct3 gene Proteins 0.000 description 2
- 230000033077 cellular process Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 231100000867 compulsive behavior Toxicity 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 230000005750 disease progression Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000008482 dysregulation Effects 0.000 description 2
- UPEZCKBFRMILAV-JMZLNJERSA-N ecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@H]([C@H](O)CCC(C)(C)O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 UPEZCKBFRMILAV-JMZLNJERSA-N 0.000 description 2
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 2
- 108700004026 gag Genes Proteins 0.000 description 2
- 238000003197 gene knockdown Methods 0.000 description 2
- 238000003364 immunohistochemistry Methods 0.000 description 2
- 238000007901 in situ hybridization Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 208000030309 inherited neurodegenerative disease Diseases 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000012092 media component Substances 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 210000004897 n-terminal region Anatomy 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 108091027963 non-coding RNA Proteins 0.000 description 2
- 102000042567 non-coding RNA Human genes 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 description 2
- 108700004029 pol Genes Proteins 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000007111 proteostasis Effects 0.000 description 2
- 230000003362 replicative effect Effects 0.000 description 2
- 238000002271 resection Methods 0.000 description 2
- 230000007441 retrograde transport Effects 0.000 description 2
- 108700004030 rev Genes Proteins 0.000 description 2
- -1 siRNA Proteins 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000008448 thought Effects 0.000 description 2
- 230000005100 tissue tropism Effects 0.000 description 2
- 238000003151 transfection method Methods 0.000 description 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 210000002845 virion Anatomy 0.000 description 2
- AQQSXKSWTNWXKR-UHFFFAOYSA-N 2-(2-phenylphenanthro[9,10-d]imidazol-3-yl)acetic acid Chemical compound C1(=CC=CC=C1)C1=NC2=C(N1CC(=O)O)C1=CC=CC=C1C=1C=CC=CC=12 AQQSXKSWTNWXKR-UHFFFAOYSA-N 0.000 description 1
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
- 108020005065 3' Flanking Region Proteins 0.000 description 1
- WBLZUCOIBUDNBV-UHFFFAOYSA-N 3-nitropropanoic acid Chemical compound OC(=O)CC[N+]([O-])=O WBLZUCOIBUDNBV-UHFFFAOYSA-N 0.000 description 1
- 108010068327 4-hydroxyphenylpyruvate dioxygenase Proteins 0.000 description 1
- 108020005029 5' Flanking Region Proteins 0.000 description 1
- 101150037123 APOE gene Proteins 0.000 description 1
- 108091010877 Allograft inflammatory factor 1 Proteins 0.000 description 1
- 102100040121 Allograft inflammatory factor 1 Human genes 0.000 description 1
- 102100034452 Alternative prion protein Human genes 0.000 description 1
- 102400001305 Amyloid A2 protein Human genes 0.000 description 1
- 101800001840 Amyloid protein AA2 Proteins 0.000 description 1
- 206010002942 Apathy Diseases 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 208000012639 Balance disease Diseases 0.000 description 1
- 102100026031 Beta-glucuronidase Human genes 0.000 description 1
- 229920002799 BoPET Polymers 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 101100380241 Caenorhabditis elegans arx-2 gene Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 208000027647 Cerebral Cortical Thinning Diseases 0.000 description 1
- 241000711969 Chandipura virus Species 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 1
- 102000016911 Deoxyribonucleases Human genes 0.000 description 1
- 108010053770 Deoxyribonucleases Proteins 0.000 description 1
- 101100118093 Drosophila melanogaster eEF1alpha2 gene Proteins 0.000 description 1
- 208000012661 Dyskinesia Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101710091045 Envelope protein Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 108700005000 Glial Fibrillary Acidic Proteins 0.000 description 1
- 102100029458 Glutamate receptor ionotropic, NMDA 2A Human genes 0.000 description 1
- 102100022630 Glutamate receptor ionotropic, NMDA 2B Human genes 0.000 description 1
- 102100022758 Glutamate receptor ionotropic, kainate 2 Human genes 0.000 description 1
- 244000048443 Gomphrena celosioides Species 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 102100028707 Homeobox protein MSX-1 Human genes 0.000 description 1
- 101000924727 Homo sapiens Alternative prion protein Proteins 0.000 description 1
- 101001125242 Homo sapiens Glutamate receptor ionotropic, NMDA 2A Proteins 0.000 description 1
- 101000972850 Homo sapiens Glutamate receptor ionotropic, NMDA 2B Proteins 0.000 description 1
- 101000903346 Homo sapiens Glutamate receptor ionotropic, kainate 2 Proteins 0.000 description 1
- 101000903313 Homo sapiens Glutamate receptor ionotropic, kainate 5 Proteins 0.000 description 1
- 101000985653 Homo sapiens Homeobox protein MSX-1 Proteins 0.000 description 1
- 101000878605 Homo sapiens Low affinity immunoglobulin epsilon Fc receptor Proteins 0.000 description 1
- 101000573901 Homo sapiens Major prion protein Proteins 0.000 description 1
- 101000979333 Homo sapiens Neurofilament light polypeptide Proteins 0.000 description 1
- 241000712003 Human respirovirus 3 Species 0.000 description 1
- 208000010158 Huntington disease-like 2 Diseases 0.000 description 1
- 208000010152 Huntington disease-like 3 Diseases 0.000 description 1
- 206010066364 Hypersexuality Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 101150090364 ICP0 gene Proteins 0.000 description 1
- 101150027427 ICP4 gene Proteins 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 206010021567 Impulsive behaviour Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 241000712902 Lassa mammarenavirus Species 0.000 description 1
- 102100038007 Low affinity immunoglobulin epsilon Fc receptor Human genes 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241000725171 Mokola lyssavirus Species 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000714177 Murine leukemia virus Species 0.000 description 1
- 241000711408 Murine respirovirus Species 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 239000005041 Mylar™ Substances 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 102100034539 Peptidyl-prolyl cis-trans isomerase A Human genes 0.000 description 1
- 108010020062 Peptidylprolyl Isomerase Proteins 0.000 description 1
- 102000009658 Peptidylprolyl Isomerase Human genes 0.000 description 1
- 206010034719 Personality change Diseases 0.000 description 1
- 206010035148 Plague Diseases 0.000 description 1
- 101710188315 Protein X Proteins 0.000 description 1
- 241000125945 Protoparvovirus Species 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 206010037742 Rabies Diseases 0.000 description 1
- 102000018120 Recombinases Human genes 0.000 description 1
- 108010091086 Recombinases Proteins 0.000 description 1
- 241000725643 Respiratory syncytial virus Species 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 241001115394 Reston ebolavirus Species 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000315672 SARS coronavirus Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 241000710960 Sindbis virus Species 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 238000012167 Small RNA sequencing Methods 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 0.000 description 1
- 102100021696 Syncytin-1 Human genes 0.000 description 1
- 201000008754 Tenosynovial giant cell tumor Diseases 0.000 description 1
- 206010043298 Testicular atrophy Diseases 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 101150004676 VGF gene Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- 241000710959 Venezuelan equine encephalitis virus Species 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 208000028752 abnormal posture Diseases 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 101150092805 actc1 gene Proteins 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 description 1
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
- VLSMHEGGTFMBBZ-UHFFFAOYSA-N alpha-Kainic acid Natural products CC(=C)C1CNC(C(O)=O)C1CC(O)=O VLSMHEGGTFMBBZ-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000002669 amniocentesis Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 201000010788 atrophy of testis Diseases 0.000 description 1
- 208000036815 beta tubulin Diseases 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 210000002932 cholinergic neuron Anatomy 0.000 description 1
- 210000004252 chorionic villi Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000029664 classic familial adenomatous polyposis Diseases 0.000 description 1
- 230000010405 clearance mechanism Effects 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 208000035647 diffuse type tenosynovial giant cell tumor Diseases 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 210000005064 dopaminergic neuron Anatomy 0.000 description 1
- 210000001029 dorsal striatum Anatomy 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000003503 early effect Effects 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 231100000318 excitotoxic Toxicity 0.000 description 1
- 230000003492 excitotoxic effect Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 230000004424 eye movement Effects 0.000 description 1
- 230000008921 facial expression Effects 0.000 description 1
- 239000006025 fining agent Substances 0.000 description 1
- 238000009459 flexible packaging Methods 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000001222 gaba-ergic neuron Anatomy 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 231100000024 genotoxic Toxicity 0.000 description 1
- 230000001738 genotoxic effect Effects 0.000 description 1
- 101150025688 ggact gene Proteins 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 102000046962 human PPIA Human genes 0.000 description 1
- 102000051631 human SERPINA1 Human genes 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 208000018879 impaired coordination Diseases 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 210000001153 interneuron Anatomy 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- VLSMHEGGTFMBBZ-OOZYFLPDSA-N kainic acid Chemical compound CC(=C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VLSMHEGGTFMBBZ-OOZYFLPDSA-N 0.000 description 1
- 229950006874 kainic acid Drugs 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 101710130522 mRNA export factor Proteins 0.000 description 1
- 238000003754 machining Methods 0.000 description 1
- 210000005171 mammalian brain Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 108091090020 miR-207 stem-loop Proteins 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000002161 motor neuron Anatomy 0.000 description 1
- 230000020763 muscle atrophy Effects 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 238000002610 neuroimaging Methods 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 108010079892 phosphoglycerol kinase Proteins 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 238000003752 polymerase chain reaction Methods 0.000 description 1
- 238000009609 prenatal screening Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 210000001176 projection neuron Anatomy 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 210000000449 purkinje cell Anatomy 0.000 description 1
- GJAWHXHKYYXBSV-UHFFFAOYSA-N quinolinic acid Chemical compound OC(=O)C1=CC=CN=C1C(O)=O GJAWHXHKYYXBSV-UHFFFAOYSA-N 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 101150098213 rev gene Proteins 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 239000013609 scAAV vector Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 230000009450 sialylation Effects 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 201000003570 spinocerebellar ataxia type 17 Diseases 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000012030 stroop test Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 210000000225 synapse Anatomy 0.000 description 1
- 210000002437 synoviocyte Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 108700004027 tat Genes Proteins 0.000 description 1
- 101150098170 tat gene Proteins 0.000 description 1
- 231100001044 testicular atrophy Toxicity 0.000 description 1
- 208000002918 testicular germ cell tumor Diseases 0.000 description 1
- 210000001103 thalamus Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 238000012034 trail making test Methods 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
- 238000009736 wetting 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/76—Viruses; Subviral particles; Bacteriophages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/76—Viruses; Subviral particles; Bacteriophages
- A61K35/761—Adenovirus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
-
- 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
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
- C12N2310/531—Stem-loop; Hairpin
-
- 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
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/32—Special delivery means, e.g. tissue-specific
-
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10023—Virus like particles [VLP]
-
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10041—Use of virus, viral particle or viral elements as a vector
- C12N2710/10043—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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/16011—Herpesviridae
- C12N2710/16041—Use of virus, viral particle or viral elements as a vector
- C12N2710/16043—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
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
- C12N2740/15041—Use of virus, viral particle or viral elements as a vector
- C12N2740/15043—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
- C12N2750/14141—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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762561843P | 2017-09-22 | 2017-09-22 | |
| US62/561,843 | 2017-09-22 | ||
| PCT/US2018/052221 WO2019060726A1 (en) | 2017-09-22 | 2018-09-21 | Variant rnai |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20200056428A KR20200056428A (ko) | 2020-05-22 |
| KR102686857B1 true KR102686857B1 (ko) | 2024-07-18 |
Family
ID=64017428
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020207011227A Active KR102686857B1 (ko) | 2017-09-22 | 2018-09-21 | 변이체 RNAi |
Country Status (18)
| Country | Link |
|---|---|
| US (3) | US11603529B2 (enExample) |
| EP (1) | EP3684932A1 (enExample) |
| JP (1) | JP7248658B2 (enExample) |
| KR (1) | KR102686857B1 (enExample) |
| CN (1) | CN111356763B (enExample) |
| AR (1) | AR113134A1 (enExample) |
| AU (2) | AU2018335410B2 (enExample) |
| BR (1) | BR112020005569A2 (enExample) |
| CA (1) | CA3076191A1 (enExample) |
| CO (1) | CO2020003187A2 (enExample) |
| IL (1) | IL273394B2 (enExample) |
| MX (2) | MX2020003095A (enExample) |
| MY (1) | MY205041A (enExample) |
| PH (1) | PH12020550117A1 (enExample) |
| SG (1) | SG11202002488UA (enExample) |
| UY (1) | UY37897A (enExample) |
| WO (1) | WO2019060726A1 (enExample) |
| ZA (1) | ZA202001586B (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MA40819B1 (fr) | 2015-02-10 | 2020-04-30 | Genzyme Corp | Variant d'arni |
| BR112018073472A2 (pt) | 2016-05-18 | 2019-08-27 | Voyager Therapeutics Inc | composições e métodos de tratamento da doença de huntington |
| SG11201909868YA (en) | 2017-05-05 | 2019-11-28 | Voyager Therapeutics Inc | Compositions and methods of treating huntington's disease |
| WO2019060726A1 (en) | 2017-09-22 | 2019-03-28 | Genzyme Corporation | Variant rnai |
| CN112980837B (zh) * | 2019-12-13 | 2023-07-04 | 深圳艾码生物科技有限公司 | 一种抑制HTT基因表达的siRNA及其前体和应用 |
| EP4133090A1 (en) * | 2020-04-07 | 2023-02-15 | Lung Biotechnology PBC | Adenoviral expression vector and methods and cell lines for production |
| CN115141848A (zh) * | 2021-03-30 | 2022-10-04 | 南京大学 | 一种用于治疗亨廷顿病的rna递送系统 |
| EP4619018A2 (en) * | 2022-11-16 | 2025-09-24 | Forge Biologics, Inc. | Adenoviral helper plasmid |
| WO2025160434A1 (en) * | 2024-01-26 | 2025-07-31 | Genzyme Corporation | Artificial micrornas targeting huntington's disease |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140163214A1 (en) | 2007-04-26 | 2014-06-12 | University Of Iowa Research Foundation | Rna interference suppression of neurodegenerative diseases and methods of use thereof |
| US20140335054A1 (en) | 2010-04-23 | 2014-11-13 | University Of Massachusetts | Cns targeting aav vectors and methods of use thereof |
| US20150099793A1 (en) | 2013-10-03 | 2015-04-09 | Washington University | RATIONAL DESIGN OF microRNA-siRNA CHIMERAS FOR MULTI-FUNCTIONAL TARGET SUPPRESSION |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001500015A (ja) | 1996-09-06 | 2001-01-09 | トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | Ｔ７ポリメラーゼを利用する組換えアデノ随伴ウイルスの誘導可能な製造方法 |
| US6995006B2 (en) | 1997-09-05 | 2006-02-07 | Targeted Genetics Corporation | Methods for generating high titer helper-free preparations of released recombinant AAV vectors |
| US6566118B1 (en) | 1997-09-05 | 2003-05-20 | Targeted Genetics Corporation | Methods for generating high titer helper-free preparations of released recombinant AAV vectors |
| JP4827353B2 (ja) | 1999-08-09 | 2011-11-30 | ターゲティッド ジェネティクス コーポレイション | 鎖内塩基対を形成するような配列の設計による、組換えウイルスベクターからの一本鎖の異種ヌクレオチド配列の発現の増大 |
| WO2001092551A2 (en) | 2000-06-01 | 2001-12-06 | University Of North Carolina At Chapel Hill | Duplexed parvovirus vectors |
| US6723551B2 (en) | 2001-11-09 | 2004-04-20 | The United States Of America As Represented By The Department Of Health And Human Services | Production of adeno-associated virus in insect cells |
| SG168422A1 (en) | 2001-11-13 | 2011-02-28 | Univ Pennsylvania | A method of detecting and/or identifying adeno-associated virus (aav) sequences and isolating novel sequences identified thereby |
| US20080274989A1 (en) | 2002-08-05 | 2008-11-06 | University Of Iowa Research Foundation | Rna Interference Suppression of Neurodegenerative Diseases and Methods of Use Thereof |
| US20050255086A1 (en) * | 2002-08-05 | 2005-11-17 | Davidson Beverly L | Nucleic acid silencing of Huntington's Disease gene |
| JP2004101787A (ja) | 2002-09-09 | 2004-04-02 | Fuji Xerox Co Ltd | 画像形成装置及び現像装置 |
| CA2881743A1 (en) | 2002-09-25 | 2004-04-08 | University Of Massachusetts | In vivo gene silencing by chemically modified and stable sirna |
| US7589189B2 (en) | 2003-05-14 | 2009-09-15 | Japan Science And Technology Agency | Inhibition of the expression of huntingtin gene |
| CA2596588C (en) * | 2005-01-31 | 2017-06-27 | University Of Iowa Research Foundation | Nucleic acid silencing of huntington's disease gene |
| WO2006119432A2 (en) | 2005-04-29 | 2006-11-09 | The Government Of The U.S.A., As Rep. By The Sec., Dept. Of Health & Human Services | Isolation, cloning and characterization of new adeno-associated virus (aav) serotypes |
| US7902352B2 (en) | 2005-05-06 | 2011-03-08 | Medtronic, Inc. | Isolated nucleic acid duplex for reducing huntington gene expression |
| EP2007795B1 (en) | 2006-03-30 | 2016-11-16 | The Board Of Trustees Of The Leland Stanford Junior University | Aav capsid proteins |
| US8173614B2 (en) * | 2007-01-03 | 2012-05-08 | Medtronic, Inc. | Therapeuting compositions comprising an RNAi agent and a neurotrophic factor and methods of use thereof |
| ES2549122T3 (es) | 2007-05-31 | 2015-10-23 | University Of Iowa Research Foundation | Reducción de toxicidad por interferencia de ARN desviada de su diana |
| CA2711585A1 (en) | 2008-02-04 | 2009-08-13 | Galapagos Nv | Molecular targets and compounds, and methods to identify the same, useful in the treatment of neurodegenerative diseases |
| EP2250183A4 (en) | 2008-02-14 | 2012-07-25 | Michael Paul Marie Gantier | SMALL IMMUNOSTIMULATORY RNAI MOLECULES |
| FR2929292A1 (fr) * | 2008-03-28 | 2009-10-02 | Exonhit Therapeutics S A Sa | Procede et methodes de diagnostic de la maladie d'alzheimer |
| US8796238B2 (en) | 2009-09-17 | 2014-08-05 | Sigma-Aldrich Co. Llc | Short RNA mimetics |
| US8663624B2 (en) | 2010-10-06 | 2014-03-04 | The Regents Of The University Of California | Adeno-associated virus virions with variant capsid and methods of use thereof |
| SG10202007803QA (en) | 2011-02-17 | 2020-09-29 | Univ Pennsylvania | Compositions and methods for altering tissue specificity and improving aav9-mediated gene transfer |
| MX374399B (es) * | 2012-02-29 | 2025-03-06 | Sangamo Biosciences Inc | Composiciones y sus usos para tratar y prevenir la enfermedad de huntington. |
| CN103224556B (zh) * | 2013-01-31 | 2015-04-15 | 清华大学 | 亨廷顿舞蹈症的靶位蛋白质及其编码基因和应用 |
| EP3068905A4 (en) * | 2013-11-11 | 2017-07-05 | Sangamo BioSciences, Inc. | Methods and compositions for treating huntington's disease |
| UA120050C2 (uk) * | 2014-03-21 | 2019-09-25 | Джензайм Корпорейшн | Генна терапія для лікування пігментного ретиніту |
| LT3137497T (lt) | 2014-05-02 | 2021-07-26 | Genzyme Corporation | Aav vektoriai, skirti tinklainės ir cns genų terapijai |
| RU2711147C2 (ru) * | 2014-05-20 | 2020-01-15 | Юниверсити Оф Айова Рисерч Фаундейшн | Терапевтические соединения для лечения болезни хантингтона |
| EA037696B1 (ru) | 2014-12-24 | 2021-05-12 | ЮНИКЕР АйПи Б.В. | Супрессия гена гентингтина, индуцированная рнк-интерференцией |
| MA40819B1 (fr) | 2015-02-10 | 2020-04-30 | Genzyme Corp | Variant d'arni |
| BR112018073472A2 (pt) | 2016-05-18 | 2019-08-27 | Voyager Therapeutics Inc | composições e métodos de tratamento da doença de huntington |
| WO2019060726A1 (en) | 2017-09-22 | 2019-03-28 | Genzyme Corporation | Variant rnai |
| WO2020028816A1 (en) * | 2018-08-03 | 2020-02-06 | Genzyme Corporation | Variant rnai against alpha-synuclein |
-
2018
- 2018-09-21 WO PCT/US2018/052221 patent/WO2019060726A1/en not_active Ceased
- 2018-09-21 IL IL273394A patent/IL273394B2/en unknown
- 2018-09-21 MY MYPI2020001372A patent/MY205041A/en unknown
- 2018-09-21 CN CN201880073881.6A patent/CN111356763B/zh active Active
- 2018-09-21 JP JP2020516666A patent/JP7248658B2/ja active Active
- 2018-09-21 UY UY0001037897A patent/UY37897A/es not_active Application Discontinuation
- 2018-09-21 MX MX2020003095A patent/MX2020003095A/es unknown
- 2018-09-21 BR BR112020005569-7A patent/BR112020005569A2/pt unknown
- 2018-09-21 CA CA3076191A patent/CA3076191A1/en active Pending
- 2018-09-21 AR ARP180102723A patent/AR113134A1/es unknown
- 2018-09-21 KR KR1020207011227A patent/KR102686857B1/ko active Active
- 2018-09-21 AU AU2018335410A patent/AU2018335410B2/en active Active
- 2018-09-21 SG SG11202002488UA patent/SG11202002488UA/en unknown
- 2018-09-21 EP EP18793503.6A patent/EP3684932A1/en active Pending
- 2018-09-21 US US16/649,042 patent/US11603529B2/en active Active
-
2020
- 2020-03-13 ZA ZA2020/01586A patent/ZA202001586B/en unknown
- 2020-03-16 PH PH12020550117A patent/PH12020550117A1/en unknown
- 2020-03-18 CO CONC2020/0003187A patent/CO2020003187A2/es unknown
- 2020-03-19 MX MX2025008949A patent/MX2025008949A/es unknown
-
2023
- 2023-02-15 US US18/169,779 patent/US12331296B2/en active Active
-
2025
- 2025-06-03 US US19/227,261 patent/US20250290075A1/en active Pending
- 2025-07-03 AU AU2025205089A patent/AU2025205089A1/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140163214A1 (en) | 2007-04-26 | 2014-06-12 | University Of Iowa Research Foundation | Rna interference suppression of neurodegenerative diseases and methods of use thereof |
| US20140335054A1 (en) | 2010-04-23 | 2014-11-13 | University Of Massachusetts | Cns targeting aav vectors and methods of use thereof |
| US20150099793A1 (en) | 2013-10-03 | 2015-04-09 | Washington University | RATIONAL DESIGN OF microRNA-siRNA CHIMERAS FOR MULTI-FUNCTIONAL TARGET SUPPRESSION |
Also Published As
| Publication number | Publication date |
|---|---|
| IL273394B1 (en) | 2024-12-01 |
| RU2020114229A (ru) | 2021-10-22 |
| MY205041A (en) | 2024-09-29 |
| CN111356763B (zh) | 2024-03-12 |
| CN111356763A (zh) | 2020-06-30 |
| IL273394B2 (en) | 2025-04-01 |
| JP7248658B2 (ja) | 2023-03-29 |
| CA3076191A1 (en) | 2019-03-28 |
| ZA202001586B (en) | 2024-01-31 |
| US12331296B2 (en) | 2025-06-17 |
| RU2020114229A3 (enExample) | 2022-02-01 |
| MX2020003095A (es) | 2020-10-15 |
| UY37897A (es) | 2019-04-30 |
| AU2025205089A1 (en) | 2025-07-24 |
| WO2019060726A1 (en) | 2019-03-28 |
| KR20200056428A (ko) | 2020-05-22 |
| US20200216848A1 (en) | 2020-07-09 |
| US11603529B2 (en) | 2023-03-14 |
| JP2020535803A (ja) | 2020-12-10 |
| MX2025008949A (es) | 2025-09-02 |
| AR113134A1 (es) | 2020-01-29 |
| US20250290075A1 (en) | 2025-09-18 |
| US20230392149A1 (en) | 2023-12-07 |
| TW201923079A (zh) | 2019-06-16 |
| PH12020550117A1 (en) | 2020-12-07 |
| EP3684932A1 (en) | 2020-07-29 |
| IL273394A (en) | 2020-05-31 |
| AU2018335410B2 (en) | 2025-04-03 |
| AU2018335410A1 (en) | 2020-05-07 |
| SG11202002488UA (en) | 2020-04-29 |
| BR112020005569A2 (pt) | 2020-10-06 |
| CO2020003187A2 (es) | 2020-04-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7526710B2 (ja) | バリアントＲＮＡｉ | |
| KR102686857B1 (ko) | 변이체 RNAi | |
| US12365895B2 (en) | Variant RNAi against alpha-synuclein | |
| RU2789647C2 (ru) | ВАРИАНТ СРЕДСТВА ДЛЯ RNAi | |
| TWI902656B (zh) | 變體ＲＮＡｉ | |
| CA2976075C (en) | Variant rnai | |
| BR112017017028B1 (pt) | Rnai variante |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20200417 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20210917 Comment text: Request for Examination of Application |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20230918 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20240417 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20240716 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20240716 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration |