TW202329985A - 用於治療cag重複序列疾病之組合物及方法 - Google Patents
用於治療cag重複序列疾病之組合物及方法 Download PDFInfo
- Publication number
- TW202329985A TW202329985A TW111137904A TW111137904A TW202329985A TW 202329985 A TW202329985 A TW 202329985A TW 111137904 A TW111137904 A TW 111137904A TW 111137904 A TW111137904 A TW 111137904A TW 202329985 A TW202329985 A TW 202329985A
- Authority
- TW
- Taiwan
- Prior art keywords
- seq
- substitution
- mismatch
- double
- strand
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 21
- 239000000203 mixture Substances 0.000 title claims abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 49
- 201000010099 disease Diseases 0.000 title claims description 32
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims abstract description 500
- 102000040650 (ribonucleotides)n+m Human genes 0.000 claims abstract description 356
- 125000003729 nucleotide group Chemical group 0.000 claims description 1137
- 239000002773 nucleotide Substances 0.000 claims description 1136
- 230000000295 complement effect Effects 0.000 claims description 823
- 238000006467 substitution reaction Methods 0.000 claims description 610
- 239000013604 expression vector Substances 0.000 claims description 293
- 238000003259 recombinant expression Methods 0.000 claims description 288
- 102000040430 polynucleotide Human genes 0.000 claims description 202
- 108091033319 polynucleotide Proteins 0.000 claims description 202
- 239000002157 polynucleotide Substances 0.000 claims description 201
- 102000009572 RNA Polymerase II Human genes 0.000 claims description 135
- 108010009460 RNA Polymerase II Proteins 0.000 claims description 135
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 134
- 241000702423 Adeno-associated virus - 2 Species 0.000 claims description 132
- 102000014450 RNA Polymerase III Human genes 0.000 claims description 130
- 108010078067 RNA Polymerase III Proteins 0.000 claims description 130
- 150000007523 nucleic acids Chemical class 0.000 claims description 99
- 102000039446 nucleic acids Human genes 0.000 claims description 98
- 108020004707 nucleic acids Proteins 0.000 claims description 98
- 239000002679 microRNA Substances 0.000 claims description 80
- 108020004414 DNA Proteins 0.000 claims description 48
- 102000053602 DNA Human genes 0.000 claims description 26
- 239000002245 particle Substances 0.000 claims description 26
- 108700011259 MicroRNAs Proteins 0.000 claims description 25
- 208000011641 Spinocerebellar disease Diseases 0.000 claims description 21
- 125000004122 cyclic group Chemical group 0.000 claims description 17
- 208000035475 disorder Diseases 0.000 claims description 17
- 210000000234 capsid Anatomy 0.000 claims description 15
- 241000700605 Viruses Species 0.000 claims description 14
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 13
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 12
- 229920001184 polypeptide Polymers 0.000 claims description 11
- 230000003612 virological effect Effects 0.000 claims description 9
- 210000003169 central nervous system Anatomy 0.000 claims description 8
- 241000702421 Dependoparvovirus Species 0.000 claims description 7
- 108091081013 MiR-33 Proteins 0.000 claims description 7
- 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 claims description 6
- 238000013519 translation Methods 0.000 claims description 6
- 230000037444 atrophy Effects 0.000 claims description 5
- 230000001603 reducing effect Effects 0.000 claims description 5
- 206010003694 Atrophy Diseases 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- 102100032187 Androgen receptor Human genes 0.000 claims description 3
- 206010058314 Dysplasia Diseases 0.000 claims description 3
- 150000002632 lipids Chemical class 0.000 claims description 3
- 239000002105 nanoparticle Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims 9
- 239000007924 injection Substances 0.000 claims 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims 3
- 101000775732 Homo sapiens Androgen receptor Proteins 0.000 claims 1
- 238000000185 intracerebroventricular administration Methods 0.000 claims 1
- 238000007913 intrathecal administration Methods 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 abstract description 20
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 241000701022 Cytomegalovirus Species 0.000 description 133
- 108090000623 proteins and genes Proteins 0.000 description 81
- 108020004999 messenger RNA Proteins 0.000 description 74
- 210000004027 cell Anatomy 0.000 description 47
- 230000014509 gene expression Effects 0.000 description 42
- 239000013598 vector Substances 0.000 description 35
- 108091070501 miRNA Proteins 0.000 description 33
- 239000004055 small Interfering RNA Substances 0.000 description 30
- 125000005647 linker group Chemical group 0.000 description 29
- 230000008685 targeting Effects 0.000 description 22
- 108091028043 Nucleic acid sequence Proteins 0.000 description 21
- 108091027967 Small hairpin RNA Proteins 0.000 description 20
- 230000006870 function Effects 0.000 description 20
- 102000004169 proteins and genes Human genes 0.000 description 20
- 150000001875 compounds Chemical class 0.000 description 19
- 108010040003 polyglutamine Proteins 0.000 description 19
- 235000018102 proteins Nutrition 0.000 description 19
- 108010020346 Polyglutamic Acid Proteins 0.000 description 18
- 229920002643 polyglutamic acid Polymers 0.000 description 18
- 229920000155 polyglutamine Polymers 0.000 description 18
- 239000002777 nucleoside Substances 0.000 description 17
- 239000013608 rAAV vector Substances 0.000 description 16
- 125000003835 nucleoside group Chemical group 0.000 description 15
- 108091007428 primary miRNA Proteins 0.000 description 15
- 239000013607 AAV vector Substances 0.000 description 14
- 210000002569 neuron Anatomy 0.000 description 13
- 108091081062 Repeated sequence (DNA) Proteins 0.000 description 12
- 238000004806 packaging method and process Methods 0.000 description 12
- 208000024891 symptom Diseases 0.000 description 12
- 238000003776 cleavage reaction Methods 0.000 description 11
- 238000012545 processing Methods 0.000 description 11
- 230000007017 scission Effects 0.000 description 11
- 108700028369 Alleles Proteins 0.000 description 10
- 102000007372 Ataxin-1 Human genes 0.000 description 10
- 108010032963 Ataxin-1 Proteins 0.000 description 10
- 108020004459 Small interfering RNA Proteins 0.000 description 10
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 10
- 230000004770 neurodegeneration Effects 0.000 description 10
- 208000015122 neurodegenerative disease Diseases 0.000 description 10
- 108091026821 Artificial microRNA Proteins 0.000 description 9
- 102100021244 Integral membrane protein GPR180 Human genes 0.000 description 9
- 210000003205 muscle Anatomy 0.000 description 9
- 102000007371 Ataxin-3 Human genes 0.000 description 8
- 108091034117 Oligonucleotide Proteins 0.000 description 8
- 238000012217 deletion Methods 0.000 description 8
- 230000037430 deletion Effects 0.000 description 8
- 230000033001 locomotion Effects 0.000 description 8
- 230000008488 polyadenylation Effects 0.000 description 8
- 230000010076 replication Effects 0.000 description 8
- 206010003591 Ataxia Diseases 0.000 description 7
- 241000282414 Homo sapiens Species 0.000 description 7
- 101000596543 Homo sapiens THAP domain-containing protein 11 Proteins 0.000 description 7
- 208000002569 Machado-Joseph Disease Diseases 0.000 description 7
- 102100035063 THAP domain-containing protein 11 Human genes 0.000 description 7
- 206010044565 Tremor Diseases 0.000 description 7
- 230000001939 inductive effect Effects 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 230000003252 repetitive effect Effects 0.000 description 7
- 230000009747 swallowing Effects 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 102000007370 Ataxin2 Human genes 0.000 description 6
- 108010032951 Ataxin2 Proteins 0.000 description 6
- 108091026890 Coding region Proteins 0.000 description 6
- 208000014094 Dystonic disease Diseases 0.000 description 6
- 102100038913 E1A-binding protein p400 Human genes 0.000 description 6
- 101000959489 Homo sapiens Protein AF-9 Proteins 0.000 description 6
- 101000957337 Homo sapiens Putative nucleotidyltransferase MAB21L1 Proteins 0.000 description 6
- 102000016304 Origin Recognition Complex Human genes 0.000 description 6
- 108010067244 Origin Recognition Complex Proteins 0.000 description 6
- 102100039686 Protein AF-9 Human genes 0.000 description 6
- 102100038753 Putative nucleotidyltransferase MAB21L1 Human genes 0.000 description 6
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 6
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 6
- 102100025368 Runt-related transcription factor 2 Human genes 0.000 description 6
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 6
- 230000027455 binding Effects 0.000 description 6
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 6
- 208000010118 dystonia Diseases 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 230000035772 mutation Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 201000003624 spinocerebellar ataxia type 1 Diseases 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 108010032953 Ataxin-7 Proteins 0.000 description 5
- 102000007368 Ataxin-7 Human genes 0.000 description 5
- 108010024682 Core Binding Factor Alpha 1 Subunit Proteins 0.000 description 5
- 101000882371 Homo sapiens E1A-binding protein p400 Proteins 0.000 description 5
- 101001005667 Homo sapiens Mastermind-like protein 2 Proteins 0.000 description 5
- 101001057193 Homo sapiens Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 Proteins 0.000 description 5
- 101000572986 Homo sapiens POU domain, class 3, transcription factor 2 Proteins 0.000 description 5
- 101000702559 Homo sapiens Probable global transcription activator SNF2L2 Proteins 0.000 description 5
- 101000807591 Homo sapiens UBAP1-MVB12-associated (UMA)-domain containing protein 1 Proteins 0.000 description 5
- 101000935117 Homo sapiens Voltage-dependent P/Q-type calcium channel subunit alpha-1A Proteins 0.000 description 5
- 101000744900 Homo sapiens Zinc finger homeobox protein 3 Proteins 0.000 description 5
- 208000027747 Kennedy disease Diseases 0.000 description 5
- 102100025130 Mastermind-like protein 2 Human genes 0.000 description 5
- 102100021070 Mediator of RNA polymerase II transcription subunit 12 Human genes 0.000 description 5
- 102100027240 Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 Human genes 0.000 description 5
- 206010028347 Muscle twitching Diseases 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 102100026459 POU domain, class 3, transcription factor 2 Human genes 0.000 description 5
- 102100037864 Probable E3 ubiquitin-protein ligase IRF2BPL Human genes 0.000 description 5
- 102100031021 Probable global transcription activator SNF2L2 Human genes 0.000 description 5
- 208000036834 Spinocerebellar ataxia type 3 Diseases 0.000 description 5
- 108700019146 Transgenes Proteins 0.000 description 5
- 102100037215 UBAP1-MVB12-associated (UMA)-domain containing protein 1 Human genes 0.000 description 5
- 102100039966 Zinc finger homeobox protein 3 Human genes 0.000 description 5
- 230000003321 amplification Effects 0.000 description 5
- 230000004424 eye movement Effects 0.000 description 5
- 230000009368 gene silencing by RNA Effects 0.000 description 5
- 238000003780 insertion Methods 0.000 description 5
- 230000037431 insertion Effects 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 210000004962 mammalian cell Anatomy 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000003199 nucleic acid amplification method Methods 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 230000009261 transgenic effect Effects 0.000 description 5
- 239000013603 viral vector Substances 0.000 description 5
- 210000002845 virion Anatomy 0.000 description 5
- 108010032947 Ataxin-3 Proteins 0.000 description 4
- 102100024507 BMP-2-inducible protein kinase Human genes 0.000 description 4
- 102000014817 CACNA1A Human genes 0.000 description 4
- 206010008748 Chorea Diseases 0.000 description 4
- 206010012289 Dementia Diseases 0.000 description 4
- 101000762370 Homo sapiens BMP-2-inducible protein kinase Proteins 0.000 description 4
- 101000749829 Homo sapiens Connector enhancer of kinase suppressor of ras 3 Proteins 0.000 description 4
- 101001005668 Homo sapiens Mastermind-like protein 3 Proteins 0.000 description 4
- 101000614988 Homo sapiens Mediator of RNA polymerase II transcription subunit 12 Proteins 0.000 description 4
- 101000599816 Homo sapiens Probable E3 ubiquitin-protein ligase IRF2BPL Proteins 0.000 description 4
- 102100025134 Mastermind-like protein 3 Human genes 0.000 description 4
- 208000002740 Muscle Rigidity Diseases 0.000 description 4
- 206010028289 Muscle atrophy Diseases 0.000 description 4
- 241000288906 Primates Species 0.000 description 4
- 108010076504 Protein Sorting Signals Proteins 0.000 description 4
- 101710156592 Putative TATA-binding protein pB263R Proteins 0.000 description 4
- 102100040296 TATA-box-binding protein Human genes 0.000 description 4
- 101710145783 TATA-box-binding protein Proteins 0.000 description 4
- 102000040945 Transcription factor Human genes 0.000 description 4
- 108091023040 Transcription factor Proteins 0.000 description 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
- 208000012601 choreatic disease Diseases 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 201000000585 muscular atrophy Diseases 0.000 description 4
- 150000003833 nucleoside derivatives Chemical class 0.000 description 4
- 230000001717 pathogenic effect Effects 0.000 description 4
- 230000001575 pathological effect Effects 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000000750 progressive effect Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 208000011580 syndromic disease Diseases 0.000 description 4
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 4
- 108020005345 3' Untranslated Regions Proteins 0.000 description 3
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 3
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 3
- 241000202702 Adeno-associated virus - 3 Species 0.000 description 3
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 3
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 3
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 3
- 241001164823 Adeno-associated virus - 7 Species 0.000 description 3
- 241001164825 Adeno-associated virus - 8 Species 0.000 description 3
- 241000649046 Adeno-associated virus 11 Species 0.000 description 3
- 102100020741 Atrophin-1 Human genes 0.000 description 3
- 208000020925 Bipolar disease Diseases 0.000 description 3
- 101000909256 Caldicellulosiruptor bescii (strain ATCC BAA-1888 / DSM 6725 / Z-1320) DNA polymerase I Proteins 0.000 description 3
- 108090000565 Capsid Proteins Proteins 0.000 description 3
- 206010008025 Cerebellar ataxia Diseases 0.000 description 3
- 102100023321 Ceruloplasmin Human genes 0.000 description 3
- 108010077544 Chromatin Proteins 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- 101710177611 DNA polymerase II large subunit Proteins 0.000 description 3
- 101710184669 DNA polymerase II small subunit Proteins 0.000 description 3
- 208000012661 Dyskinesia Diseases 0.000 description 3
- 201000011240 Frontotemporal dementia Diseases 0.000 description 3
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 3
- 108090000246 Histone acetyltransferases Proteins 0.000 description 3
- 102000003893 Histone acetyltransferases Human genes 0.000 description 3
- 101000785083 Homo sapiens Atrophin-1 Proteins 0.000 description 3
- 101000869796 Homo sapiens Microprocessor complex subunit DGCR8 Proteins 0.000 description 3
- 101000915806 Homo sapiens Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform Proteins 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 102100032459 Microprocessor complex subunit DGCR8 Human genes 0.000 description 3
- 208000008238 Muscle Spasticity Diseases 0.000 description 3
- 206010052904 Musculoskeletal stiffness Diseases 0.000 description 3
- 101000902592 Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1) DNA polymerase Proteins 0.000 description 3
- 241000714474 Rous sarcoma virus Species 0.000 description 3
- 102100029014 Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform Human genes 0.000 description 3
- 230000005856 abnormality Effects 0.000 description 3
- 238000000137 annealing Methods 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000000988 bone and bone Anatomy 0.000 description 3
- 230000030833 cell death Effects 0.000 description 3
- 210000003483 chromatin Anatomy 0.000 description 3
- 210000000349 chromosome Anatomy 0.000 description 3
- 229940104302 cytosine Drugs 0.000 description 3
- 230000002950 deficient Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000030279 gene silencing Effects 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 230000000977 initiatory effect Effects 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 210000004498 neuroglial cell Anatomy 0.000 description 3
- 108091027963 non-coding RNA Proteins 0.000 description 3
- 102000042567 non-coding RNA Human genes 0.000 description 3
- 206010029864 nystagmus Diseases 0.000 description 3
- 230000009437 off-target effect Effects 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- 239000013609 scAAV vector Substances 0.000 description 3
- 208000018198 spasticity Diseases 0.000 description 3
- 210000004500 stellate cell Anatomy 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 230000005026 transcription initiation Effects 0.000 description 3
- 108091006108 transcriptional coactivators Proteins 0.000 description 3
- 241001529453 unidentified herpesvirus Species 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 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 2
- 108020005065 3' Flanking Region Proteins 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- 108020005029 5' Flanking Region Proteins 0.000 description 2
- 108020003589 5' Untranslated Regions Proteins 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 102100033647 Activity-regulated cytoskeleton-associated protein Human genes 0.000 description 2
- -1 Atrophin Proteins 0.000 description 2
- 241000713704 Bovine immunodeficiency virus Species 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 230000004543 DNA replication Effects 0.000 description 2
- 208000003164 Diplopia Diseases 0.000 description 2
- 241000713730 Equine infectious anemia virus Species 0.000 description 2
- 208000001308 Fasciculation Diseases 0.000 description 2
- 241000713800 Feline immunodeficiency virus Species 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- 101000695522 Homo sapiens Synaptophysin Proteins 0.000 description 2
- 108050004784 Huntingtin Proteins 0.000 description 2
- 102000016252 Huntingtin Human genes 0.000 description 2
- 201000006347 Intellectual Disability Diseases 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- 208000015592 Involuntary movements Diseases 0.000 description 2
- 241000713666 Lentivirus Species 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 102000003792 Metallothionein Human genes 0.000 description 2
- 108090000157 Metallothionein Proteins 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 208000007101 Muscle Cramp Diseases 0.000 description 2
- 102100022437 Myotonin-protein kinase Human genes 0.000 description 2
- 208000029726 Neurodevelopmental disease Diseases 0.000 description 2
- 108010070047 Notch Receptors Proteins 0.000 description 2
- 102000005650 Notch Receptors Human genes 0.000 description 2
- 102100029534 Nuclear receptor subfamily 2 group E member 1 Human genes 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 2
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 2
- 108091036407 Polyadenylation Proteins 0.000 description 2
- 108010058956 Protein Phosphatase 2 Proteins 0.000 description 2
- 102000006478 Protein Phosphatase 2 Human genes 0.000 description 2
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 101000599815 Rattus norvegicus Probable E3 ubiquitin-protein ligase IRF2BPL Proteins 0.000 description 2
- 206010040030 Sensory loss Diseases 0.000 description 2
- 241000713311 Simian immunodeficiency virus Species 0.000 description 2
- 102000004874 Synaptophysin Human genes 0.000 description 2
- 108090001076 Synaptophysin Proteins 0.000 description 2
- 102000006467 TATA-Box Binding Protein Human genes 0.000 description 2
- 108010044281 TATA-Box Binding Protein Proteins 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 102000006290 Transcription Factor TFIID Human genes 0.000 description 2
- 108010083268 Transcription Factor TFIID Proteins 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 101150084233 ago2 gene Proteins 0.000 description 2
- 108010080146 androgen receptors Proteins 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000003111 delayed effect Effects 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
- 239000003623 enhancer Substances 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 238000012226 gene silencing method Methods 0.000 description 2
- 102000050055 human SYP Human genes 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 230000002025 microglial effect Effects 0.000 description 2
- 210000002161 motor neuron Anatomy 0.000 description 2
- 230000017311 musculoskeletal movement, spinal reflex action Effects 0.000 description 2
- 230000004031 neuronal differentiation Effects 0.000 description 2
- 206010030875 ophthalmoplegia Diseases 0.000 description 2
- 201000004481 ossifying fibromyxoid tumor Diseases 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 2
- 230000001124 posttranscriptional effect Effects 0.000 description 2
- 230000001850 reproductive effect Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 229940113082 thymine Drugs 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000005030 transcription termination Effects 0.000 description 2
- 230000002103 transcriptional effect Effects 0.000 description 2
- 108091006107 transcriptional repressors Proteins 0.000 description 2
- 230000002463 transducing effect Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- FDKWRPBBCBCIGA-REOHCLBHSA-N (2r)-2-azaniumyl-3-$l^{1}-selanylpropanoate Chemical compound [Se]C[C@H](N)C(O)=O FDKWRPBBCBCIGA-REOHCLBHSA-N 0.000 description 1
- OFNXOACBUMGOPC-HZYVHMACSA-N 5'-hydroxystreptomycin 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](CO)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 OFNXOACBUMGOPC-HZYVHMACSA-N 0.000 description 1
- 208000036443 AIPL1-related retinopathy Diseases 0.000 description 1
- 101710159080 Aconitate hydratase A Proteins 0.000 description 1
- 101710159078 Aconitate hydratase B Proteins 0.000 description 1
- 206010069754 Acquired gene mutation Diseases 0.000 description 1
- 208000007876 Acrospiroma Diseases 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 102000004321 Atrophin-1 Human genes 0.000 description 1
- 108090000806 Atrophin-1 Proteins 0.000 description 1
- 208000017785 Autosomal dominant epilepsy with auditory features Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 108060000903 Beta-catenin Proteins 0.000 description 1
- 102000015735 Beta-catenin Human genes 0.000 description 1
- 208000024400 Blepharophimosis-intellectual disability syndrome, Ohdo type Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 1
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010006100 Bradykinesia Diseases 0.000 description 1
- 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 description 1
- 101150041164 Cacna1a gene Proteins 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 208000015879 Cerebellar disease Diseases 0.000 description 1
- 206010008754 Choreoathetosis Diseases 0.000 description 1
- 208000037051 Chromosomal Instability Diseases 0.000 description 1
- 108010060434 Co-Repressor Proteins Proteins 0.000 description 1
- 102000008169 Co-Repressor Proteins Human genes 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- FDKWRPBBCBCIGA-UWTATZPHSA-N D-Selenocysteine Natural products [Se]C[C@@H](N)C(O)=O FDKWRPBBCBCIGA-UWTATZPHSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- 102000001477 Deubiquitinating Enzymes Human genes 0.000 description 1
- 108010093668 Deubiquitinating Enzymes Proteins 0.000 description 1
- 206010012559 Developmental delay Diseases 0.000 description 1
- 241000255925 Diptera Species 0.000 description 1
- 241000255601 Drosophila melanogaster Species 0.000 description 1
- 206010013887 Dysarthria Diseases 0.000 description 1
- 206010013952 Dysphonia Diseases 0.000 description 1
- 101710202499 E1A-binding protein p400 Proteins 0.000 description 1
- 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 1
- 241000283086 Equidae Species 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 102000004678 Exoribonucleases Human genes 0.000 description 1
- 108010002700 Exoribonucleases Proteins 0.000 description 1
- 201000003727 FG syndrome Diseases 0.000 description 1
- 208000033890 FG syndrome type 1 Diseases 0.000 description 1
- 241000714165 Feline leukemia virus Species 0.000 description 1
- 241000714174 Feline sarcoma virus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 230000006370 G0 arrest Effects 0.000 description 1
- 230000037057 G1 phase arrest Effects 0.000 description 1
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 102100022901 Histone acetyltransferase KAT2A Human genes 0.000 description 1
- 102100022103 Histone-lysine N-methyltransferase 2A Human genes 0.000 description 1
- 108050002855 Histone-lysine N-methyltransferase 2A Proteins 0.000 description 1
- 101001046967 Homo sapiens Histone acetyltransferase KAT2A Proteins 0.000 description 1
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 description 1
- 101000633503 Homo sapiens Nuclear receptor subfamily 2 group E member 1 Proteins 0.000 description 1
- 101000780643 Homo sapiens Protein argonaute-2 Proteins 0.000 description 1
- 101000857682 Homo sapiens Runt-related transcription factor 2 Proteins 0.000 description 1
- 101100421722 Homo sapiens SMARCA2 gene Proteins 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 101150010142 IRF2BPL gene Proteins 0.000 description 1
- 206010065042 Immune reconstitution inflammatory syndrome Diseases 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 208000001242 Lujan-Fryns syndrome Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 102100025136 Macrosialin Human genes 0.000 description 1
- 101710179284 Mediator of RNA polymerase II transcription subunit 12 Proteins 0.000 description 1
- 201000008468 Meier-Gorlin syndrome 1 Diseases 0.000 description 1
- 201000008466 Meier-Gorlin syndrome 2 Diseases 0.000 description 1
- 206010027374 Mental impairment Diseases 0.000 description 1
- 208000034819 Mobility Limitation Diseases 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 206010057269 Mucoepidermoid carcinoma Diseases 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 241000714177 Murine leukemia virus Species 0.000 description 1
- 101100144701 Mus musculus Drosha gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 108010021466 Mutant Proteins Proteins 0.000 description 1
- 102000008300 Mutant Proteins Human genes 0.000 description 1
- 208000002033 Myoclonus Diseases 0.000 description 1
- 206010068871 Myotonic dystrophy Diseases 0.000 description 1
- 208000000737 Nicolaides-Baraitser syndrome Diseases 0.000 description 1
- 102000007999 Nuclear Proteins Human genes 0.000 description 1
- 108010089610 Nuclear Proteins Proteins 0.000 description 1
- 101710088761 Nuclear receptor subfamily 2 group E member 1 Proteins 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 201000003048 Ohdo syndrome Diseases 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 102100030030 Origin recognition complex subunit 4 Human genes 0.000 description 1
- 101710201850 Origin recognition complex subunit 4 Proteins 0.000 description 1
- 108091081548 Palindromic sequence Proteins 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 208000027089 Parkinsonian disease Diseases 0.000 description 1
- 206010034010 Parkinsonism Diseases 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 206010034620 Peripheral sensory neuropathy Diseases 0.000 description 1
- 206010034719 Personality change Diseases 0.000 description 1
- 108700019535 Phosphoprotein Phosphatases Proteins 0.000 description 1
- 102000045595 Phosphoprotein Phosphatases Human genes 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 101710178065 Probable E3 ubiquitin-protein ligase IRF2BPL Proteins 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- 102100029812 Protein S100-A12 Human genes 0.000 description 1
- 101710110949 Protein S100-A12 Proteins 0.000 description 1
- 102100034207 Protein argonaute-2 Human genes 0.000 description 1
- 101710150114 Protein rep Proteins 0.000 description 1
- 208000025535 REM sleep behavior disease Diseases 0.000 description 1
- 102000044126 RNA-Binding Proteins Human genes 0.000 description 1
- 101710105008 RNA-binding protein Proteins 0.000 description 1
- 108091030071 RNAI Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 101710152114 Replication protein Proteins 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 208000005793 Restless legs syndrome Diseases 0.000 description 1
- 108010081750 Reticulin Proteins 0.000 description 1
- 201000007737 Retinal degeneration Diseases 0.000 description 1
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 201000001542 Schneiderian carcinoma Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000020221 Short stature Diseases 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 108091081024 Start codon Proteins 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 108010022394 Threonine synthase Proteins 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 description 1
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 206010046798 Uterine leiomyoma Diseases 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 208000010094 Visna Diseases 0.000 description 1
- 102100025330 Voltage-dependent P/Q-type calcium channel subunit alpha-1A Human genes 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 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 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 210000004507 artificial chromosome Anatomy 0.000 description 1
- 230000008335 axon cargo transport Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 230000008436 biogenesis Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000037182 bone density Effects 0.000 description 1
- 230000014461 bone development Effects 0.000 description 1
- 230000034127 bone morphogenesis Effects 0.000 description 1
- 229940112869 bone morphogenetic protein Drugs 0.000 description 1
- 206010071135 branchio-oto-renal syndrome Diseases 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 230000008777 canonical pathway Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000021617 central nervous system development Effects 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 230000006726 chronic neurodegeneration Effects 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 201000006754 cone-rod dystrophy Diseases 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 210000000806 cranial fontanelle Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 231100000868 delusion Toxicity 0.000 description 1
- 239000005549 deoxyribonucleoside Substances 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 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
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 102000004419 dihydrofolate reductase Human genes 0.000 description 1
- 208000029444 double vision Diseases 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000005584 early death Effects 0.000 description 1
- 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 1
- 230000013020 embryo development Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 208000001936 exophthalmos Diseases 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 230000004077 genetic alteration Effects 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 201000000079 gynecomastia Diseases 0.000 description 1
- 230000010370 hearing loss Effects 0.000 description 1
- 231100000888 hearing loss Toxicity 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 201000005133 hidradenoma Diseases 0.000 description 1
- OFNXOACBUMGOPC-UHFFFAOYSA-N hydroxystreptomycin Natural products CNC1C(O)C(O)C(CO)OC1OC1C(C=O)(O)C(CO)OC1OC1C(N=C(N)N)C(O)C(N=C(N)N)C(O)C1O OFNXOACBUMGOPC-UHFFFAOYSA-N 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003933 intellectual function Effects 0.000 description 1
- 230000007154 intracellular accumulation Effects 0.000 description 1
- OKPOKMCPHKVCPP-UHFFFAOYSA-N isoorientaline Natural products C1=C(O)C(OC)=CC(CC2C3=CC(OC)=C(O)C=C3CCN2C)=C1 OKPOKMCPHKVCPP-UHFFFAOYSA-N 0.000 description 1
- 201000003445 large cell neuroendocrine carcinoma Diseases 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 231100000875 loss of motor control Toxicity 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 230000036630 mental development Effects 0.000 description 1
- 108091007426 microRNA precursor Proteins 0.000 description 1
- 208000008275 microscopic colitis Diseases 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 208000001491 myopia Diseases 0.000 description 1
- 230000004379 myopia Effects 0.000 description 1
- 230000000626 neurodegenerative effect Effects 0.000 description 1
- 230000007472 neurodevelopment Effects 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000008193 neuromotor development Effects 0.000 description 1
- 208000018360 neuromuscular disease Diseases 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 231100000862 numbness Toxicity 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 230000004072 osteoblast differentiation Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 210000002706 plastid Anatomy 0.000 description 1
- 108010054442 polyalanine Proteins 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 230000023603 positive regulation of transcription initiation, DNA-dependent Effects 0.000 description 1
- 230000006555 post-translational control Effects 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 208000026526 progressive weakness Diseases 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000004461 rapid eye movement Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- JTQHYPFKHZLTSH-UHFFFAOYSA-N reticulin Natural products COC1CC(OC2C(CO)OC(OC3C(O)CC(OC4C(C)OC(CC4OC)OC5CCC6(C)C7CCC8(C)C(CCC8(O)C7CC=C6C5)C(C)O)OC3C)C(O)C2OC)OC(C)C1O JTQHYPFKHZLTSH-UHFFFAOYSA-N 0.000 description 1
- 230000004258 retinal degeneration Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000002342 ribonucleoside Substances 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 230000001711 saccadic effect Effects 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229940055619 selenocysteine Drugs 0.000 description 1
- ZKZBPNGNEQAJSX-UHFFFAOYSA-N selenocysteine Natural products [SeH]CC(N)C(O)=O ZKZBPNGNEQAJSX-UHFFFAOYSA-N 0.000 description 1
- 235000016491 selenocysteine Nutrition 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 201000005572 sensory peripheral neuropathy Diseases 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 230000006403 short-term memory Effects 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[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 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 230000022379 skeletal muscle tissue development Effects 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 208000022925 sleep disturbance Diseases 0.000 description 1
- 208000026473 slurred speech Diseases 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 230000037439 somatic mutation Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000000515 tooth Anatomy 0.000 description 1
- 230000010474 transient expression Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000009752 translational inhibition Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 230000005740 tumor formation Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 201000007954 uterine fibroid Diseases 0.000 description 1
- 230000029812 viral genome replication Effects 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
- C12N15/11—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
- 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
- A61P25/28—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- 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
- C12N2320/50—Methods for regulating/modulating their activity
-
- 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)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Psychology (AREA)
- Virology (AREA)
- Dermatology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202163253070P | 2021-10-06 | 2021-10-06 | |
| US63/253,070 | 2021-10-06 | ||
| US202263339363P | 2022-05-06 | 2022-05-06 | |
| US63/339,363 | 2022-05-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202329985A true TW202329985A (zh) | 2023-08-01 |
Family
ID=85804745
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW111137904A TW202329985A (zh) | 2021-10-06 | 2022-10-05 | 用於治療cag重複序列疾病之組合物及方法 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20240425856A1 (https=) |
| EP (1) | EP4413137A4 (https=) |
| JP (1) | JP2024543782A (https=) |
| AU (1) | AU2022358732A1 (https=) |
| CA (1) | CA3232737A1 (https=) |
| IL (1) | IL311638A (https=) |
| MX (1) | MX2024004119A (https=) |
| TW (1) | TW202329985A (https=) |
| WO (1) | WO2023060104A1 (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2024253981A1 (en) * | 2023-04-05 | 2025-11-06 | Board Of Trustees Of Southern Illinois University | Compositions and methods for treating cag repeat diseases |
| US20240360443A1 (en) * | 2023-04-09 | 2024-10-31 | Dystrogen Gene Therapies Inc. | Nucleic acid molecule and use of the nucleic acid molecule in therapy of diseases induced by expansion of trinucleotide cag repeats |
| AU2024332679A1 (en) * | 2023-08-31 | 2026-04-16 | Iris Medicine, Inc. | Methods and compositions for treating ggggcc repeat expansion diseases |
| WO2025137623A1 (en) * | 2023-12-22 | 2025-06-26 | Iris Medicine, Inc. | Methods and compositions for treating ctg repeat expansion diseases |
| WO2025213123A1 (en) * | 2024-04-05 | 2025-10-09 | Encoded Therapeutics, Inc. | Methods and compositions for increasing expression of ube3a |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL243776B1 (pl) * | 2013-09-02 | 2023-10-09 | Inst Chemii Bioorganicznej Polskiej Akademii Nauk | Cząsteczka kwasu nukleinowego, kaseta ekspresyjna, wektor ekspresyjny, komórka eukariotycznego gospodarza i zastosowanie cząsteczki kwasu nukleinowego w terapii chorób wywoływanych ekspansją trójnukleotydowych powtórzeń typu CAG |
| EP3359667A1 (en) * | 2015-10-05 | 2018-08-15 | ProQR Therapeutics II B.V. | Use of single-stranded antisense oligonucleotide in prevention or treatment of genetic diseases involving a trinucleotide repeat expansion |
| WO2018152523A1 (en) * | 2017-02-20 | 2018-08-23 | Northwestern University | Use of trinucleotide repeat rnas to treat cancer |
-
2022
- 2022-10-05 WO PCT/US2022/077572 patent/WO2023060104A1/en not_active Ceased
- 2022-10-05 TW TW111137904A patent/TW202329985A/zh unknown
- 2022-10-05 JP JP2024521180A patent/JP2024543782A/ja active Pending
- 2022-10-05 EP EP22879440.0A patent/EP4413137A4/en active Pending
- 2022-10-05 AU AU2022358732A patent/AU2022358732A1/en active Pending
- 2022-10-05 US US18/699,523 patent/US20240425856A1/en active Pending
- 2022-10-05 IL IL311638A patent/IL311638A/en unknown
- 2022-10-05 CA CA3232737A patent/CA3232737A1/en active Pending
-
2024
- 2024-04-03 MX MX2024004119A patent/MX2024004119A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MX2024004119A (es) | 2024-12-06 |
| EP4413137A1 (en) | 2024-08-14 |
| JP2024543782A (ja) | 2024-11-26 |
| US20240425856A1 (en) | 2024-12-26 |
| CA3232737A1 (en) | 2023-04-13 |
| IL311638A (en) | 2024-05-01 |
| WO2023060104A1 (en) | 2023-04-13 |
| AU2022358732A1 (en) | 2024-04-11 |
| EP4413137A4 (en) | 2026-02-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW202329985A (zh) | 用於治療cag重複序列疾病之組合物及方法 | |
| US9523093B2 (en) | Huntington's disease therapeutic compounds | |
| US9074207B2 (en) | Modified human U1snRNA molecule, a gene encoding for the modified human U1snRNA molecule, an expression vector including the gene, and the use thereof in gene therapy | |
| JP7565218B2 (ja) | 筋萎縮性側索硬化症および脊髄に関連する障害の治療 | |
| CN111108198A (zh) | 治疗亨廷顿病的组合物和方法 | |
| AU2017268382A1 (en) | Compositions and methods of treating huntington's disease | |
| EP4454654A2 (en) | Treatment of amyotrophic lateral sclerosis (als) | |
| US20220010314A1 (en) | Rnai induced reduction of ataxin-3 for the treatment of spinocerebellar ataxia type 3 | |
| JP2023532864A (ja) | 導入遺伝子発現系 | |
| JP2024517710A (ja) | 蝸牛に形質導入するためのアデノ随伴ウイルスベクター | |
| US20200248204A1 (en) | Methods of treating genetic hearing loss | |
| JP7787094B2 (ja) | 筋萎縮性側索硬化症を治療するためのアンチセンス配列 | |
| TW202504620A (zh) | 用於治療cag重複疾病之組成物和方法 | |
| EP4642911A2 (en) | Compositions and methods for regulating mapt | |
| EP4165194A2 (en) | Compositions and methods for treating kcnq4-associated hearing loss | |
| Deutsch et al. | AAV-Mediated CRISPRi and RNAi Based Gene Silencing in Mouse Hippocampal Neurons. Cells 2021, 10, 324 | |
| CN121294435A (zh) | 靶向fus的rna干扰方法、核酸及其应用 | |
| HK40122722A (zh) | 用於调控mapt的组合物和方法 | |
| HK1236224B (en) | Huntington's disease therapeutic compounds | |
| HK1236224A1 (en) | Huntington's disease therapeutic compounds |