JP2022527015A - リソソーム障害のための遺伝子治療 - Google Patents
リソソーム障害のための遺伝子治療 Download PDFInfo
- Publication number
- JP2022527015A JP2022527015A JP2021559976A JP2021559976A JP2022527015A JP 2022527015 A JP2022527015 A JP 2022527015A JP 2021559976 A JP2021559976 A JP 2021559976A JP 2021559976 A JP2021559976 A JP 2021559976A JP 2022527015 A JP2022527015 A JP 2022527015A
- Authority
- JP
- Japan
- Prior art keywords
- nucleic acid
- raav
- disease
- gene
- protein
- 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.)
- Pending
Links
- 208000015439 Lysosomal storage disease Diseases 0.000 title claims description 13
- 238000001415 gene therapy Methods 0.000 title description 13
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 358
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 332
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 309
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 309
- 230000014509 gene expression Effects 0.000 claims abstract description 217
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 138
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 70
- 201000010099 disease Diseases 0.000 claims abstract description 58
- 238000000034 method Methods 0.000 claims abstract description 57
- 230000008685 targeting Effects 0.000 claims abstract description 53
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 42
- 208000015114 central nervous system disease Diseases 0.000 claims abstract description 39
- 102100021244 Integral membrane protein GPR180 Human genes 0.000 claims description 95
- 101000997662 Homo sapiens Lysosomal acid glucosylceramidase Proteins 0.000 claims description 84
- 102100033342 Lysosomal acid glucosylceramidase Human genes 0.000 claims description 84
- 102000004169 proteins and genes Human genes 0.000 claims description 84
- 238000002347 injection Methods 0.000 claims description 68
- 239000007924 injection Substances 0.000 claims description 68
- 102100026232 Transmembrane protein 106B Human genes 0.000 claims description 49
- 108091026890 Coding region Proteins 0.000 claims description 48
- 102100026882 Alpha-synuclein Human genes 0.000 claims description 47
- 101000834898 Homo sapiens Alpha-synuclein Proteins 0.000 claims description 47
- 101000834926 Homo sapiens Transmembrane protein 106B Proteins 0.000 claims description 47
- 102100040243 Microtubule-associated protein tau Human genes 0.000 claims description 41
- 102100020983 Lysosome membrane protein 2 Human genes 0.000 claims description 38
- 108090000565 Capsid Proteins Proteins 0.000 claims description 35
- 102100023321 Ceruloplasmin Human genes 0.000 claims description 35
- 102100037632 Progranulin Human genes 0.000 claims description 35
- 102100028496 Galactocerebrosidase Human genes 0.000 claims description 29
- 108700019146 Transgenes Proteins 0.000 claims description 27
- 102100033499 Interleukin-34 Human genes 0.000 claims description 26
- 101000795117 Homo sapiens Triggering receptor expressed on myeloid cells 2 Proteins 0.000 claims description 25
- 102100029678 Triggering receptor expressed on myeloid cells 2 Human genes 0.000 claims description 25
- 230000002441 reversible effect Effects 0.000 claims description 25
- 241000702421 Dependoparvovirus Species 0.000 claims description 24
- 108091005488 SCARB2 Proteins 0.000 claims description 23
- 102100027346 GTP cyclohydrolase 1 Human genes 0.000 claims description 22
- 102100022721 40S ribosomal protein S25 Human genes 0.000 claims description 21
- 101000678929 Homo sapiens 40S ribosomal protein S25 Proteins 0.000 claims description 21
- 101000862581 Homo sapiens GTP cyclohydrolase 1 Proteins 0.000 claims description 21
- 101000860395 Homo sapiens Galactocerebrosidase Proteins 0.000 claims description 20
- 102100021633 Cathepsin B Human genes 0.000 claims description 19
- 101000898449 Homo sapiens Cathepsin B Proteins 0.000 claims description 19
- 102100027814 Non-lysosomal glucosylceramidase Human genes 0.000 claims description 18
- 101000859679 Homo sapiens Non-lysosomal glucosylceramidase Proteins 0.000 claims description 17
- 101000854862 Homo sapiens Vacuolar protein sorting-associated protein 35 Proteins 0.000 claims description 17
- 102100026263 Sphingomyelin phosphodiesterase Human genes 0.000 claims description 17
- 102100020822 Vacuolar protein sorting-associated protein 35 Human genes 0.000 claims description 17
- 230000002093 peripheral effect Effects 0.000 claims description 16
- 101000785978 Homo sapiens Sphingomyelin phosphodiesterase Proteins 0.000 claims description 15
- 101000712725 Homo sapiens Ras-related protein Rab-7L1 Proteins 0.000 claims description 13
- 102000019355 Synuclein Human genes 0.000 claims description 13
- 108050006783 Synuclein Proteins 0.000 claims description 13
- 208000034799 Tauopathies Diseases 0.000 claims description 12
- 230000004770 neurodegeneration Effects 0.000 claims description 11
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 11
- 102100033100 Ras-related protein Rab-7L1 Human genes 0.000 claims description 9
- 241000702423 Adeno-associated virus - 2 Species 0.000 claims description 8
- 238000007913 intrathecal administration Methods 0.000 claims description 8
- 238000010253 intravenous injection Methods 0.000 claims description 6
- 101000998132 Homo sapiens Interleukin-34 Proteins 0.000 claims description 5
- 210000003703 cisterna magna Anatomy 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 3
- 101000891579 Homo sapiens Microtubule-associated protein tau Proteins 0.000 claims description 2
- 101710114165 Progranulin Proteins 0.000 claims 1
- 108010007100 Pulmonary Surfactant-Associated Protein A Proteins 0.000 claims 1
- 102100027773 Pulmonary surfactant-associated protein A2 Human genes 0.000 claims 1
- 208000018737 Parkinson disease Diseases 0.000 abstract description 58
- 208000015872 Gaucher disease Diseases 0.000 abstract description 47
- 238000011282 treatment Methods 0.000 abstract description 46
- 239000000203 mixture Substances 0.000 abstract description 39
- 239000000047 product Substances 0.000 description 163
- 239000013598 vector Substances 0.000 description 123
- ZHMWOVGZCINIHW-FTYOSCRSSA-N 1-D-1,2-anhydro-myo-inositol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H]2O[C@H]21 ZHMWOVGZCINIHW-FTYOSCRSSA-N 0.000 description 105
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 88
- 235000018102 proteins Nutrition 0.000 description 81
- 239000013608 rAAV vector Substances 0.000 description 74
- 210000004027 cell Anatomy 0.000 description 69
- 238000010586 diagram Methods 0.000 description 57
- 239000002679 microRNA Substances 0.000 description 53
- 108700011259 MicroRNAs Proteins 0.000 description 50
- 108010012809 Progranulins Proteins 0.000 description 50
- 102000019204 Progranulins Human genes 0.000 description 49
- 241000699670 Mus sp. Species 0.000 description 48
- 108091028043 Nucleic acid sequence Proteins 0.000 description 46
- 102100036197 Prosaposin Human genes 0.000 description 44
- 101710152403 Prosaposin Proteins 0.000 description 44
- 230000002452 interceptive effect Effects 0.000 description 44
- 239000000546 pharmaceutical excipient Substances 0.000 description 43
- 101710115937 Microtubule-associated protein tau Proteins 0.000 description 40
- 239000013612 plasmid Substances 0.000 description 39
- 230000035772 mutation Effects 0.000 description 36
- 108090000765 processed proteins & peptides Proteins 0.000 description 36
- 230000000694 effects Effects 0.000 description 32
- 239000002773 nucleotide Substances 0.000 description 32
- 125000003729 nucleotide group Chemical group 0.000 description 32
- 201000011240 Frontotemporal dementia Diseases 0.000 description 28
- 230000035508 accumulation Effects 0.000 description 24
- 238000009825 accumulation Methods 0.000 description 24
- 210000004556 brain Anatomy 0.000 description 23
- 101710181549 Interleukin-34 Proteins 0.000 description 21
- 238000003556 assay Methods 0.000 description 21
- 210000004962 mammalian cell Anatomy 0.000 description 21
- 101100095198 Homo sapiens SCARB2 gene Proteins 0.000 description 20
- 108020004684 Internal Ribosome Entry Sites Proteins 0.000 description 20
- 208000024827 Alzheimer disease Diseases 0.000 description 18
- 241000282412 Homo Species 0.000 description 18
- 125000003275 alpha amino acid group Chemical group 0.000 description 18
- 210000000349 chromosome Anatomy 0.000 description 18
- 210000005260 human cell Anatomy 0.000 description 18
- 208000024891 symptom Diseases 0.000 description 17
- 238000000338 in vitro Methods 0.000 description 16
- 230000002132 lysosomal effect Effects 0.000 description 16
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 15
- 208000009829 Lewy Body Disease Diseases 0.000 description 15
- 201000002832 Lewy body dementia Diseases 0.000 description 15
- 102000003802 alpha-Synuclein Human genes 0.000 description 14
- 108090000185 alpha-Synuclein Proteins 0.000 description 14
- 238000010172 mouse model Methods 0.000 description 14
- 239000012634 fragment Substances 0.000 description 13
- 239000013607 AAV vector Substances 0.000 description 12
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 description 12
- 208000035475 disorder Diseases 0.000 description 12
- 239000000758 substrate Substances 0.000 description 12
- 101150003696 gba-1 gene Proteins 0.000 description 11
- 102220341636 rs780972896 Human genes 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 10
- 108020004459 Small interfering RNA Proteins 0.000 description 10
- 238000010361 transduction Methods 0.000 description 10
- 230000026683 transduction Effects 0.000 description 10
- 108010042681 Galactosylceramidase Proteins 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 101150078881 TMEM106B gene Proteins 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- 238000002965 ELISA Methods 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 8
- 108091027967 Small hairpin RNA Proteins 0.000 description 8
- POQRWMRXUOPCLD-GZXCKHLVSA-N beta-D-glucosyl-N-(tetracosanoyl)sphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@H]([C@H](O)\C=C\CCCCCCCCCCCCC)CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O POQRWMRXUOPCLD-GZXCKHLVSA-N 0.000 description 8
- 230000000295 complement effect Effects 0.000 description 8
- 230000002950 deficient Effects 0.000 description 8
- 238000012417 linear regression Methods 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 230000002018 overexpression Effects 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 238000001890 transfection Methods 0.000 description 8
- 101000584785 Homo sapiens Ras-related protein Rab-7a Proteins 0.000 description 7
- 238000011529 RT qPCR Methods 0.000 description 7
- 102100030019 Ras-related protein Rab-7a Human genes 0.000 description 7
- 230000003542 behavioural effect Effects 0.000 description 7
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 7
- 150000002632 lipids Chemical class 0.000 description 7
- 210000003712 lysosome Anatomy 0.000 description 7
- 230000001868 lysosomic effect Effects 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 239000004055 small Interfering RNA Substances 0.000 description 7
- 241000701447 unidentified baculovirus Species 0.000 description 7
- 239000002299 complementary DNA Substances 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000004048 modification Effects 0.000 description 6
- 238000012986 modification Methods 0.000 description 6
- 208000005264 motor neuron disease Diseases 0.000 description 6
- 108090000712 Cathepsin B Proteins 0.000 description 5
- 102000004225 Cathepsin B Human genes 0.000 description 5
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 description 5
- 239000012097 Lipofectamine 2000 Substances 0.000 description 5
- 101150070547 MAPT gene Proteins 0.000 description 5
- 102100025136 Macrosialin Human genes 0.000 description 5
- 208000001089 Multiple system atrophy Diseases 0.000 description 5
- -1 PRGN Proteins 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 230000007812 deficiency Effects 0.000 description 5
- 230000030279 gene silencing Effects 0.000 description 5
- 238000005462 in vivo assay Methods 0.000 description 5
- 238000001802 infusion Methods 0.000 description 5
- 238000007914 intraventricular administration Methods 0.000 description 5
- 210000003734 kidney Anatomy 0.000 description 5
- 210000000066 myeloid cell Anatomy 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 238000003753 real-time PCR Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 239000013603 viral vector Substances 0.000 description 5
- 230000003612 virological effect Effects 0.000 description 5
- YXHLJMWYDTXDHS-IRFLANFNSA-N 7-aminoactinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=C(N)C=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 YXHLJMWYDTXDHS-IRFLANFNSA-N 0.000 description 4
- 108700012813 7-aminoactinomycin D Proteins 0.000 description 4
- 108091026821 Artificial microRNA Proteins 0.000 description 4
- 101150035856 CTSB gene Proteins 0.000 description 4
- 101100282794 Caenorhabditis elegans gba-2 gene Proteins 0.000 description 4
- 206010012289 Dementia Diseases 0.000 description 4
- 238000012286 ELISA Assay Methods 0.000 description 4
- 101150004665 GCH1 gene Proteins 0.000 description 4
- 208000020916 Gaucher disease type II Diseases 0.000 description 4
- 208000028735 Gaucher disease type III Diseases 0.000 description 4
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 description 4
- 101150027225 Il34 gene Proteins 0.000 description 4
- 208000026072 Motor neurone disease Diseases 0.000 description 4
- 208000010577 Niemann-Pick disease type C Diseases 0.000 description 4
- 101150002602 Psap gene Proteins 0.000 description 4
- 101150110423 SNCA gene Proteins 0.000 description 4
- 101150118355 Smpd1 gene Proteins 0.000 description 4
- 208000007930 Type C Niemann-Pick Disease Diseases 0.000 description 4
- 101150035098 VPS35 gene Proteins 0.000 description 4
- 230000006399 behavior Effects 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 4
- 101150022753 galc gene Proteins 0.000 description 4
- 101150073411 gba-2 gene Proteins 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000001361 intraarterial administration Methods 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 230000002025 microglial effect Effects 0.000 description 4
- 208000033808 peripheral neuropathy Diseases 0.000 description 4
- 239000002924 silencing RNA Substances 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 239000012096 transfection reagent Substances 0.000 description 4
- 102100027831 14-3-3 protein theta Human genes 0.000 description 3
- 108020005345 3' Untranslated Regions Proteins 0.000 description 3
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 3
- 101150024624 GRN gene Proteins 0.000 description 3
- 208000020322 Gaucher disease type I Diseases 0.000 description 3
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 3
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 3
- 101100426014 Homo sapiens TREM2 gene Proteins 0.000 description 3
- 108091092195 Intron Proteins 0.000 description 3
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 3
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 239000012124 Opti-MEM Substances 0.000 description 3
- 206010033799 Paralysis Diseases 0.000 description 3
- 101150108283 RpS25 gene Proteins 0.000 description 3
- 102000017852 Saposin Human genes 0.000 description 3
- 108050007079 Saposin Proteins 0.000 description 3
- 101150085127 TREM2 gene Proteins 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000008499 blood brain barrier function Effects 0.000 description 3
- 210000001218 blood-brain barrier Anatomy 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 208000010877 cognitive disease Diseases 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000002596 correlated effect Effects 0.000 description 3
- 230000001054 cortical effect Effects 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000004064 dysfunction Effects 0.000 description 3
- 239000013604 expression vector Substances 0.000 description 3
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 3
- 210000002149 gonad Anatomy 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 231100000225 lethality Toxicity 0.000 description 3
- 230000015100 lysosomal transport Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 230000000926 neurological effect Effects 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 108091007428 primary miRNA Proteins 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 2
- 108700028369 Alleles Proteins 0.000 description 2
- 241001203868 Autographa californica Species 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 208000012661 Dyskinesia Diseases 0.000 description 2
- 108010017544 Glucosylceramidase Proteins 0.000 description 2
- 229930186217 Glycolipid Natural products 0.000 description 2
- 101100368517 Homo sapiens SNCA gene Proteins 0.000 description 2
- 102000004157 Hydrolases Human genes 0.000 description 2
- 108090000604 Hydrolases Proteins 0.000 description 2
- 108010009254 Lysosomal-Associated Membrane Protein 1 Proteins 0.000 description 2
- 108010064171 Lysosome-Associated Membrane Glycoproteins Proteins 0.000 description 2
- 102000014944 Lysosome-Associated Membrane Glycoproteins Human genes 0.000 description 2
- 102100035133 Lysosome-associated membrane glycoprotein 1 Human genes 0.000 description 2
- 208000034819 Mobility Limitation Diseases 0.000 description 2
- 238000002123 RNA extraction Methods 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 101710201924 Sphingomyelin phosphodiesterase 1 Proteins 0.000 description 2
- 101710095280 Sphingomyelinase C 1 Proteins 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 101710175911 Transmembrane protein 106B Proteins 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 2
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 238000013320 baculovirus expression vector system Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000012742 biochemical analysis Methods 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000002798 bone marrow cell Anatomy 0.000 description 2
- 210000000234 capsid Anatomy 0.000 description 2
- 210000001715 carotid artery Anatomy 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 230000001149 cognitive effect Effects 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000007850 degeneration Effects 0.000 description 2
- 210000001787 dendrite Anatomy 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000009088 enzymatic function Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 150000002339 glycosphingolipids Chemical class 0.000 description 2
- 102000045630 human GBA Human genes 0.000 description 2
- 238000010191 image analysis Methods 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 239000007928 intraperitoneal injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 201000010901 lateral sclerosis Diseases 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000007758 minimum essential medium Substances 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 230000007659 motor function Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000002981 neuropathic effect Effects 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 238000000424 optical density measurement Methods 0.000 description 2
- 208000021090 palsy Diseases 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 230000001124 posttranscriptional effect Effects 0.000 description 2
- 230000001323 posttranslational effect Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 238000010814 radioimmunoprecipitation assay Methods 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 239000013609 scAAV vector Substances 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 210000002504 synaptic vesicle Anatomy 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 102100037563 40S ribosomal protein S2 Human genes 0.000 description 1
- 108020003589 5' Untranslated Regions Proteins 0.000 description 1
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 1
- 241000202702 Adeno-associated virus - 3 Species 0.000 description 1
- 241000580270 Adeno-associated virus - 4 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
- 241000649045 Adeno-associated virus 10 Species 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 241000473391 Archosargus rhomboidalis Species 0.000 description 1
- 108091032955 Bacterial small RNA Proteins 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 208000018240 Bone Marrow Failure disease Diseases 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- 102100025222 CD63 antigen Human genes 0.000 description 1
- 101100282787 Caenorhabditis elegans gba-1 gene Proteins 0.000 description 1
- 101100126625 Caenorhabditis elegans itr-1 gene Proteins 0.000 description 1
- 206010009696 Clumsiness Diseases 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 108010005843 Cysteine Proteases Proteins 0.000 description 1
- 102000005927 Cysteine Proteases Human genes 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- LHQIJBMDNUYRAM-AWFVSMACSA-N D-erythro-biopterin Chemical compound N1=C(N)NC(=O)C2=NC([C@H](O)[C@H](O)C)=CN=C21 LHQIJBMDNUYRAM-AWFVSMACSA-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
- 208000035976 Developmental Disabilities Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108700039887 Essential Genes Proteins 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 1
- 108010023555 GTP Cyclohydrolase Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 1
- 206010018341 Gliosis Diseases 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101001098029 Homo sapiens 40S ribosomal protein S2 Proteins 0.000 description 1
- 101000934368 Homo sapiens CD63 antigen Proteins 0.000 description 1
- 101001066129 Homo sapiens Glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100022297 Integrin alpha-X Human genes 0.000 description 1
- LHQIJBMDNUYRAM-UHFFFAOYSA-N L-erythro-Biopterin Natural products N1=C(N)NC(=O)C2=NC(C(O)C(O)C)=CN=C21 LHQIJBMDNUYRAM-UHFFFAOYSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 108010009491 Lysosomal-Associated Membrane Protein 2 Proteins 0.000 description 1
- 102100038225 Lysosome-associated membrane glycoprotein 2 Human genes 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- PKVZBNCYEICAQP-UHFFFAOYSA-N Mecamylamine hydrochloride Chemical compound Cl.C1CC2C(C)(C)C(NC)(C)C1C2 PKVZBNCYEICAQP-UHFFFAOYSA-N 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 108091033773 MiR-155 Proteins 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 206010061296 Motor dysfunction Diseases 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 101710083785 Non-lysosomal glucosylceramidase Proteins 0.000 description 1
- 206010033661 Pancytopenia Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 108091034057 RNA (poly(A)) Proteins 0.000 description 1
- 102000009572 RNA Polymerase II Human genes 0.000 description 1
- 108010009460 RNA Polymerase II Proteins 0.000 description 1
- 108091008103 RNA aptamers Proteins 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010000605 Ribosomal Proteins Proteins 0.000 description 1
- 102000002278 Ribosomal Proteins Human genes 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 238000010818 SYBR green PCR Master Mix Methods 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 102000006467 TATA-Box Binding Protein Human genes 0.000 description 1
- 108010044281 TATA-Box Binding Protein Proteins 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 241001492404 Woodchuck hepatitis virus Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229960002964 adalimumab Drugs 0.000 description 1
- 150000003838 adenosines Chemical class 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000004900 autophagic degradation Effects 0.000 description 1
- 230000006741 behavioral dysfunction Effects 0.000 description 1
- 238000009227 behaviour therapy Methods 0.000 description 1
- WPIHMWBQRSAMDE-YCZTVTEBSA-N beta-D-galactosyl-(1->4)-beta-D-galactosyl-N-(pentacosanoyl)sphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO[C@@H]1O[C@H](CO)[C@H](O[C@@H]2O[C@H](CO)[C@H](O)[C@H](O)[C@H]2O)[C@H](O)[C@H]1O)[C@H](O)\C=C\CCCCCCCCCCCCC WPIHMWBQRSAMDE-YCZTVTEBSA-N 0.000 description 1
- HHJTWTPUPVQKNA-JIAPQYILSA-N beta-D-glucosylsphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HHJTWTPUPVQKNA-JIAPQYILSA-N 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 238000003236 bicinchoninic acid assay Methods 0.000 description 1
- 230000006696 biosynthetic metabolic pathway Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 108010006025 bovine growth hormone Proteins 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000003271 compound fluorescence assay Methods 0.000 description 1
- 238000002247 constant time method Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 230000022770 endosome transport Effects 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 238000002641 enzyme replacement therapy Methods 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 229960005167 everolimus Drugs 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 230000004424 eye movement Effects 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000002073 fluorescence micrograph Methods 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000002594 fluoroscopy Methods 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000009368 gene silencing by RNA Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000009650 gentamicin protection assay Methods 0.000 description 1
- 230000007387 gliosis Effects 0.000 description 1
- 150000002305 glucosylceramides Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 206010019847 hepatosplenomegaly Diseases 0.000 description 1
- 102000057063 human MAPT Human genes 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 101150059888 lysM gene Proteins 0.000 description 1
- 108010045758 lysosomal proteins Proteins 0.000 description 1
- 229940124302 mTOR inhibitor Drugs 0.000 description 1
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 210000001259 mesencephalon Anatomy 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000004973 motor coordination Effects 0.000 description 1
- 210000000337 motor cortex Anatomy 0.000 description 1
- 230000003387 muscular Effects 0.000 description 1
- 230000001016 myotrophic effect Effects 0.000 description 1
- DDOVBCWVTOHGCU-QMXMISKISA-N n-[(e,2s,3r)-3-hydroxy-1-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxynonadec-4-en-2-yl]octadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)N[C@H]([C@H](O)\C=C\CCCCCCCCCCCCCC)CO[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O DDOVBCWVTOHGCU-QMXMISKISA-N 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 229960005027 natalizumab Drugs 0.000 description 1
- 230000012106 negative regulation of microtubule depolymerization Effects 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000002482 oligosaccharides Polymers 0.000 description 1
- 239000000668 oral spray Substances 0.000 description 1
- 229940041678 oral spray Drugs 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 210000000578 peripheral nerve Anatomy 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- 238000007747 plating Methods 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 210000000063 presynaptic terminal Anatomy 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000007111 proteostasis Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- HHJTWTPUPVQKNA-PIIMIWFASA-N psychosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O HHJTWTPUPVQKNA-PIIMIWFASA-N 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 102000016914 ras Proteins Human genes 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000007441 retrograde transport Effects 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 238000010839 reverse transcription Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 231100000279 safety data Toxicity 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000004137 sphingolipid metabolism Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 102000013498 tau Proteins Human genes 0.000 description 1
- 108010026424 tau Proteins Proteins 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 210000003412 trans-golgi network Anatomy 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Images
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
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0085—Brain, e.g. brain implants; Spinal cord
-
- 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
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
-
- 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
-
- 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
- C12N15/1137—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 against enzymes
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
- C12N9/2405—Glucanases
- C12N9/2408—Glucanases acting on alpha -1,4-glucosidic bonds
- C12N9/2411—Amylases
- C12N9/2414—Alpha-amylase (3.2.1.1.)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
- C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y302/01045—Glucosylceramidase (3.2.1.45), i.e. beta-glucocerebrosidase
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2207/00—Modified animals
- A01K2207/20—Animals treated with compounds which are neither proteins nor nucleic acids
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
- A01K2267/0318—Animal model for neurodegenerative disease, e.g. non- Alzheimer's
-
- 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 N.A.
-
- 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
- C12N2320/31—Combination therapy
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2330/00—Production
- C12N2330/50—Biochemical production, i.e. in a transformed host cell
- C12N2330/51—Specially adapted 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
- 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)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- General Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biophysics (AREA)
- Microbiology (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Virology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Toxicology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Psychology (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Cell Biology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (19)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962831840P | 2019-04-10 | 2019-04-10 | |
| US201962831846P | 2019-04-10 | 2019-04-10 | |
| US201962831856P | 2019-04-10 | 2019-04-10 | |
| US201962832223P | 2019-04-10 | 2019-04-10 | |
| US62/831,856 | 2019-04-10 | ||
| US62/832,223 | 2019-04-10 | ||
| US62/831,846 | 2019-04-10 | ||
| US62/831,840 | 2019-04-10 | ||
| US201962934450P | 2019-11-12 | 2019-11-12 | |
| US62/934,450 | 2019-11-12 | ||
| US201962954089P | 2019-12-27 | 2019-12-27 | |
| US62/954,089 | 2019-12-27 | ||
| US202062960471P | 2020-01-13 | 2020-01-13 | |
| US62/960,471 | 2020-01-13 | ||
| US202062988665P | 2020-03-12 | 2020-03-12 | |
| US62/988,665 | 2020-03-12 | ||
| US202062990246P | 2020-03-16 | 2020-03-16 | |
| US62/990,246 | 2020-03-16 | ||
| PCT/US2020/027658 WO2020210615A1 (fr) | 2019-04-10 | 2020-04-10 | Thérapies géniques pour troubles lysosomaux |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2022527015A true JP2022527015A (ja) | 2022-05-27 |
Family
ID=79032950
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021559976A Pending JP2022527015A (ja) | 2019-04-10 | 2020-04-10 | リソソーム障害のための遺伝子治療 |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP3952923A4 (fr) |
| JP (1) | JP2022527015A (fr) |
| KR (1) | KR20210150487A (fr) |
| CN (1) | CN114025806A (fr) |
| IL (1) | IL286582A (fr) |
| MX (1) | MX2021012467A (fr) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10648001B2 (en) * | 2012-07-11 | 2020-05-12 | Sangamo Therapeutics, Inc. | Method of treating mucopolysaccharidosis type I or II |
| SG11201509419QA (en) * | 2013-05-15 | 2015-12-30 | Univ Minnesota | Adeno-associated virus mediated gene transfer to the central nervous system |
| US10967073B2 (en) * | 2015-05-07 | 2021-04-06 | The Mclean Hospital Corporation | Glucocerebrosidase gene therapy for Parkinson's disease |
| TWI832036B (zh) * | 2017-08-03 | 2024-02-11 | 美商航海家醫療公司 | 用於aav之遞送之組合物及方法 |
-
2020
- 2020-04-10 JP JP2021559976A patent/JP2022527015A/ja active Pending
- 2020-04-10 MX MX2021012467A patent/MX2021012467A/es unknown
- 2020-04-10 EP EP20787456.1A patent/EP3952923A4/fr active Pending
- 2020-04-10 CN CN202080027713.0A patent/CN114025806A/zh not_active Withdrawn
- 2020-04-10 KR KR1020217036238A patent/KR20210150487A/ko unknown
-
2021
- 2021-09-22 IL IL286582A patent/IL286582A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20210150487A (ko) | 2021-12-10 |
| CN114025806A (zh) | 2022-02-08 |
| MX2021012467A (es) | 2021-12-10 |
| EP3952923A1 (fr) | 2022-02-16 |
| IL286582A (en) | 2021-12-01 |
| EP3952923A4 (fr) | 2023-10-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7389828B2 (ja) | ライソゾーム病の遺伝子治療 | |
| JP7254815B2 (ja) | ライソゾーム病の遺伝子治療 | |
| US20200318115A1 (en) | Gene therapies for lysosomal disorders | |
| CA3134841A1 (fr) | Therapies geniques pour troubles lysosomaux | |
| US20220211871A1 (en) | Gene therapies for lysosomal disorders | |
| JP2022526823A (ja) | リソソーム障害のための遺伝子療法 | |
| JP2022527015A (ja) | リソソーム障害のための遺伝子治療 |