CN117120619A - 用于治疗与葡萄糖神经酰胺酶β缺陷相关的神经病症的组合物和方法 - Google Patents
用于治疗与葡萄糖神经酰胺酶β缺陷相关的神经病症的组合物和方法 Download PDFInfo
- Publication number
- CN117120619A CN117120619A CN202180066205.8A CN202180066205A CN117120619A CN 117120619 A CN117120619 A CN 117120619A CN 202180066205 A CN202180066205 A CN 202180066205A CN 117120619 A CN117120619 A CN 117120619A
- Authority
- CN
- China
- Prior art keywords
- seq
- amino acid
- sequence
- acid sequence
- nucleotide sequence
- 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
- 238000000034 method Methods 0.000 title claims abstract description 96
- 102100033342 Lysosomal acid glucosylceramidase Human genes 0.000 title claims description 317
- 101000997662 Homo sapiens Lysosomal acid glucosylceramidase Proteins 0.000 title claims description 231
- 239000000203 mixture Substances 0.000 title abstract description 18
- 230000007812 deficiency Effects 0.000 title abstract description 5
- 208000012902 Nervous system disease Diseases 0.000 title description 6
- 208000025966 Neurological disease Diseases 0.000 title description 2
- 239000002245 particle Substances 0.000 claims abstract description 131
- 230000002708 enhancing effect Effects 0.000 claims abstract description 112
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 86
- 230000014509 gene expression Effects 0.000 claims abstract description 77
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 71
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 43
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 41
- 101150028412 GBA gene Proteins 0.000 claims abstract description 15
- 230000002829 reductive effect Effects 0.000 claims abstract description 8
- 125000003729 nucleotide group Chemical group 0.000 claims description 957
- 239000002773 nucleotide Substances 0.000 claims description 906
- 230000003612 virological effect Effects 0.000 claims description 361
- 150000001413 amino acids Chemical group 0.000 claims description 230
- 230000027455 binding Effects 0.000 claims description 190
- 150000007523 nucleic acids Chemical class 0.000 claims description 154
- 102000039446 nucleic acids Human genes 0.000 claims description 149
- 108020004707 nucleic acids Proteins 0.000 claims description 149
- 230000004048 modification Effects 0.000 claims description 139
- 238000012986 modification Methods 0.000 claims description 139
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 136
- 108091070501 miRNA Proteins 0.000 claims description 124
- 108090000565 Capsid Proteins Proteins 0.000 claims description 108
- 102100023321 Ceruloplasmin Human genes 0.000 claims description 107
- 210000004027 cell Anatomy 0.000 claims description 107
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 100
- 108010017544 Glucosylceramidase Proteins 0.000 claims description 86
- 238000006467 substitution reaction Methods 0.000 claims description 80
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 73
- 229940024606 amino acid Drugs 0.000 claims description 72
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 71
- 210000001519 tissue Anatomy 0.000 claims description 70
- 125000006850 spacer group Chemical group 0.000 claims description 69
- 229920001184 polypeptide Polymers 0.000 claims description 64
- 208000015872 Gaucher disease Diseases 0.000 claims description 57
- 239000003623 enhancer Substances 0.000 claims description 55
- 108091029500 miR-183 stem-loop Proteins 0.000 claims description 51
- 108700019146 Transgenes Proteins 0.000 claims description 50
- 230000035772 mutation Effects 0.000 claims description 50
- 230000000295 complement effect Effects 0.000 claims description 35
- 210000003169 central nervous system Anatomy 0.000 claims description 34
- 230000003014 reinforcing effect Effects 0.000 claims description 32
- 230000007017 scission Effects 0.000 claims description 31
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 claims description 27
- 230000008488 polyadenylation Effects 0.000 claims description 27
- 238000003776 cleavage reaction Methods 0.000 claims description 26
- 201000010099 disease Diseases 0.000 claims description 26
- 239000013598 vector Substances 0.000 claims description 26
- 230000008685 targeting Effects 0.000 claims description 25
- 102000004961 Furin Human genes 0.000 claims description 23
- 108090001126 Furin Proteins 0.000 claims description 23
- 230000000694 effects Effects 0.000 claims description 23
- 230000002132 lysosomal effect Effects 0.000 claims description 23
- 150000003408 sphingolipids Chemical class 0.000 claims description 23
- 239000012634 fragment Substances 0.000 claims description 22
- 208000018360 neuromuscular disease Diseases 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 230000003213 activating effect Effects 0.000 claims description 20
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 claims description 19
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 claims description 19
- 201000002832 Lewy body dementia Diseases 0.000 claims description 18
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 18
- 108091007780 MiR-122 Proteins 0.000 claims description 17
- 210000004185 liver Anatomy 0.000 claims description 17
- 108091051828 miR-122 stem-loop Proteins 0.000 claims description 17
- 241000282414 Homo sapiens Species 0.000 claims description 13
- 230000001965 increasing effect Effects 0.000 claims description 13
- 108020004999 messenger RNA Proteins 0.000 claims description 13
- 102100037935 Polyubiquitin-C Human genes 0.000 claims description 12
- 108010056354 Ubiquitin C Proteins 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 230000002981 neuropathic effect Effects 0.000 claims description 12
- 210000001103 thalamus Anatomy 0.000 claims description 12
- 210000000133 brain stem Anatomy 0.000 claims description 11
- -1 e.g. Proteins 0.000 claims description 11
- 101000979333 Homo sapiens Neurofilament light polypeptide Proteins 0.000 claims description 10
- 208000009829 Lewy Body Disease Diseases 0.000 claims description 10
- 102100023057 Neurofilament light polypeptide Human genes 0.000 claims description 10
- 101800004937 Protein C Proteins 0.000 claims description 10
- 101800001700 Saposin-D Proteins 0.000 claims description 10
- 238000003556 assay Methods 0.000 claims description 10
- 238000001990 intravenous administration Methods 0.000 claims description 10
- 102100026031 Beta-glucuronidase Human genes 0.000 claims description 9
- 101000933465 Homo sapiens Beta-glucuronidase Proteins 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 108091079658 miR-142-1 stem-loop Proteins 0.000 claims description 9
- 108091071830 miR-142-2 stem-loop Proteins 0.000 claims description 9
- 230000000626 neurodegenerative effect Effects 0.000 claims description 9
- 238000011282 treatment Methods 0.000 claims description 9
- 102000006734 Beta-Globulins Human genes 0.000 claims description 8
- 108010087504 Beta-Globulins Proteins 0.000 claims description 8
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 claims description 8
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 claims description 8
- 210000001638 cerebellum Anatomy 0.000 claims description 8
- 206010064571 Gene mutation Diseases 0.000 claims description 7
- 101710172711 Structural protein Proteins 0.000 claims description 7
- 230000001580 bacterial effect Effects 0.000 claims description 7
- 230000003394 haemopoietic effect Effects 0.000 claims description 7
- 210000001577 neostriatum Anatomy 0.000 claims description 7
- 210000000278 spinal cord Anatomy 0.000 claims description 7
- 102000004657 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Human genes 0.000 claims description 6
- 108010003721 Calcium-Calmodulin-Dependent Protein Kinase Type 2 Proteins 0.000 claims description 6
- 208000001089 Multiple system atrophy Diseases 0.000 claims description 6
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 claims description 6
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 claims description 6
- 201000006417 multiple sclerosis Diseases 0.000 claims description 6
- 208000002320 spinal muscular atrophy Diseases 0.000 claims description 6
- 239000000758 substrate Substances 0.000 claims description 6
- URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 claims description 5
- 108010072388 Methyl-CpG-Binding Protein 2 Proteins 0.000 claims description 5
- 210000004556 brain Anatomy 0.000 claims description 5
- 239000012530 fluid Substances 0.000 claims description 5
- 230000002232 neuromuscular Effects 0.000 claims description 5
- 230000002093 peripheral effect Effects 0.000 claims description 5
- 210000002966 serum Anatomy 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 101100524317 Adeno-associated virus 2 (isolate Srivastava/1982) Rep40 gene Proteins 0.000 claims description 4
- 101100524319 Adeno-associated virus 2 (isolate Srivastava/1982) Rep52 gene Proteins 0.000 claims description 4
- 101100524321 Adeno-associated virus 2 (isolate Srivastava/1982) Rep68 gene Proteins 0.000 claims description 4
- 101100524324 Adeno-associated virus 2 (isolate Srivastava/1982) Rep78 gene Proteins 0.000 claims description 4
- 101100228196 Caenorhabditis elegans gly-4 gene Proteins 0.000 claims description 4
- 102000053187 Glucuronidase Human genes 0.000 claims description 4
- 108010060309 Glucuronidase Proteins 0.000 claims description 4
- 102100037872 Intercellular adhesion molecule 2 Human genes 0.000 claims description 4
- 101710148794 Intercellular adhesion molecule 2 Proteins 0.000 claims description 4
- 102000001435 Synapsin Human genes 0.000 claims description 4
- 108050009621 Synapsin Proteins 0.000 claims description 4
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims description 4
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 claims description 4
- 210000004962 mammalian cell Anatomy 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 238000002604 ultrasonography Methods 0.000 claims description 4
- 101150044789 Cap gene Proteins 0.000 claims description 3
- 108700028146 Genetic Enhancer Elements Proteins 0.000 claims description 3
- 241000238631 Hexapoda Species 0.000 claims description 3
- 102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 claims description 3
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 claims description 3
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 claims description 3
- 102000047918 Myelin Basic Human genes 0.000 claims description 3
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 claims description 3
- 102100040990 Platelet-derived growth factor subunit B Human genes 0.000 claims description 3
- 101710103494 Platelet-derived growth factor subunit B Proteins 0.000 claims description 3
- 206010044565 Tremor Diseases 0.000 claims description 3
- 229960004205 carbidopa Drugs 0.000 claims description 3
- TZFNLOMSOLWIDK-JTQLQIEISA-N carbidopa (anhydrous) Chemical compound NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 TZFNLOMSOLWIDK-JTQLQIEISA-N 0.000 claims description 3
- 108010038421 metabotropic glutamate receptor 2 Proteins 0.000 claims description 3
- 229960003089 pramipexole Drugs 0.000 claims description 3
- FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 claims description 3
- 101150066583 rep gene Proteins 0.000 claims description 3
- 229960001879 ropinirole Drugs 0.000 claims description 3
- UHSKFQJFRQCDBE-UHFFFAOYSA-N ropinirole Chemical compound CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 claims description 3
- 229960003179 rotigotine Drugs 0.000 claims description 3
- KFQYTPMOWPVWEJ-INIZCTEOSA-N rotigotine Chemical compound CCCN([C@@H]1CC2=CC=CC(O)=C2CC1)CCC1=CC=CS1 KFQYTPMOWPVWEJ-INIZCTEOSA-N 0.000 claims description 3
- 108050005273 Amino acid transporters Proteins 0.000 claims description 2
- 102000034263 Amino acid transporters Human genes 0.000 claims description 2
- 102100036912 Desmin Human genes 0.000 claims description 2
- 108010044052 Desmin Proteins 0.000 claims description 2
- 206010018341 Gliosis Diseases 0.000 claims description 2
- 102100027377 HBS1-like protein Human genes 0.000 claims description 2
- 101001009070 Homo sapiens HBS1-like protein Proteins 0.000 claims description 2
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 2
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 2
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims description 2
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 claims description 2
- 102100026893 Troponin T, cardiac muscle Human genes 0.000 claims description 2
- 101710165323 Troponin T, cardiac muscle Proteins 0.000 claims description 2
- 230000002159 abnormal effect Effects 0.000 claims description 2
- GIJXKZJWITVLHI-PMOLBWCYSA-N benzatropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(C=1C=CC=CC=1)C1=CC=CC=C1 GIJXKZJWITVLHI-PMOLBWCYSA-N 0.000 claims description 2
- 229960001081 benzatropine Drugs 0.000 claims description 2
- 210000004369 blood Anatomy 0.000 claims description 2
- 239000008280 blood Substances 0.000 claims description 2
- 239000000812 cholinergic antagonist Substances 0.000 claims description 2
- 239000000544 cholinesterase inhibitor Substances 0.000 claims description 2
- 210000005045 desmin Anatomy 0.000 claims description 2
- 229960003530 donepezil Drugs 0.000 claims description 2
- 229940052760 dopamine agonists Drugs 0.000 claims description 2
- 239000003136 dopamine receptor stimulating agent Substances 0.000 claims description 2
- 230000009977 dual effect Effects 0.000 claims description 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
- 238000005538 encapsulation Methods 0.000 claims description 2
- 238000002641 enzyme replacement therapy Methods 0.000 claims description 2
- 229960003980 galantamine Drugs 0.000 claims description 2
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 claims description 2
- 230000007387 gliosis Effects 0.000 claims description 2
- 210000000777 hematopoietic system Anatomy 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 238000000185 intracerebroventricular administration Methods 0.000 claims description 2
- 230000000366 juvenile effect Effects 0.000 claims description 2
- 229960004502 levodopa Drugs 0.000 claims description 2
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 claims description 2
- 229960004640 memantine Drugs 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 229940044551 receptor antagonist Drugs 0.000 claims description 2
- 239000002464 receptor antagonist Substances 0.000 claims description 2
- 230000009467 reduction Effects 0.000 claims description 2
- 229960004136 rivastigmine Drugs 0.000 claims description 2
- 210000002027 skeletal muscle Anatomy 0.000 claims description 2
- 239000002679 microRNA Substances 0.000 claims 3
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 claims 2
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 claims 1
- 102100039124 Methyl-CpG-binding protein 2 Human genes 0.000 claims 1
- 108700028031 Myelin Basic Proteins 0.000 claims 1
- 102400000827 Saposin-D Human genes 0.000 claims 1
- 239000000835 fiber Substances 0.000 claims 1
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 claims 1
- 229960004801 imipramine Drugs 0.000 claims 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims 1
- 229960004768 irinotecan Drugs 0.000 claims 1
- 229950004994 meglitinide Drugs 0.000 claims 1
- 238000012384 transportation and delivery Methods 0.000 abstract description 10
- 241000702421 Dependoparvovirus Species 0.000 abstract description 6
- 238000001727 in vivo Methods 0.000 abstract description 2
- 238000000338 in vitro Methods 0.000 abstract 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 265
- 235000001014 amino acid Nutrition 0.000 description 77
- 235000018102 proteins Nutrition 0.000 description 62
- 210000000234 capsid Anatomy 0.000 description 32
- 241000701022 Cytomegalovirus Species 0.000 description 30
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 29
- 230000000670 limiting effect Effects 0.000 description 20
- 101001040800 Homo sapiens Integral membrane protein GPR180 Proteins 0.000 description 17
- 102100021244 Integral membrane protein GPR180 Human genes 0.000 description 17
- 108091023045 Untranslated Region Proteins 0.000 description 16
- 208000035475 disorder Diseases 0.000 description 16
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 16
- 102000040430 polynucleotide Human genes 0.000 description 15
- 108091033319 polynucleotide Proteins 0.000 description 15
- 239000002157 polynucleotide Substances 0.000 description 15
- 239000000306 component Substances 0.000 description 14
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 14
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical group CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 14
- 239000013607 AAV vector Substances 0.000 description 13
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 13
- OLTSGVZGKOFTHZ-UHFFFAOYSA-N P.P.P.P.P.P.P.P.P Chemical compound P.P.P.P.P.P.P.P.P OLTSGVZGKOFTHZ-UHFFFAOYSA-N 0.000 description 13
- 230000010076 replication Effects 0.000 description 13
- 241001164825 Adeno-associated virus - 8 Species 0.000 description 12
- 241000649045 Adeno-associated virus 10 Species 0.000 description 12
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 11
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 11
- 108091092195 Intron Proteins 0.000 description 11
- 108020005176 AU Rich Elements Proteins 0.000 description 10
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 10
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 10
- 101100170937 Mus musculus Dnmt1 gene Proteins 0.000 description 10
- 102000010292 Peptide Elongation Factor 1 Human genes 0.000 description 10
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 10
- 210000002950 fibroblast Anatomy 0.000 description 10
- 210000003594 spinal ganglia Anatomy 0.000 description 10
- 208000020916 Gaucher disease type II Diseases 0.000 description 9
- 108091027559 Mir-96 microRNA Proteins 0.000 description 9
- 239000013604 expression vector Substances 0.000 description 9
- 108091023796 miR-182 stem-loop Proteins 0.000 description 9
- 108091086713 miR-96 stem-loop Proteins 0.000 description 9
- 108091070961 miR-96-3 stem-loop Proteins 0.000 description 9
- 238000011144 upstream manufacturing Methods 0.000 description 9
- 229930024421 Adenine Natural products 0.000 description 8
- 241000649046 Adeno-associated virus 11 Species 0.000 description 8
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 8
- 229960000643 adenine Drugs 0.000 description 8
- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 8
- 241000202702 Adeno-associated virus - 3 Species 0.000 description 7
- 241001164823 Adeno-associated virus - 7 Species 0.000 description 7
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 7
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 7
- 108091081024 Start codon Proteins 0.000 description 7
- 108091036066 Three prime untranslated region Proteins 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 229940104302 cytosine Drugs 0.000 description 7
- 210000002569 neuron Anatomy 0.000 description 7
- 229940113082 thymine Drugs 0.000 description 7
- 238000010361 transduction Methods 0.000 description 7
- 230000026683 transduction Effects 0.000 description 7
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 6
- 241000649047 Adeno-associated virus 12 Species 0.000 description 6
- 239000004475 Arginine Substances 0.000 description 6
- 108020004705 Codon Proteins 0.000 description 6
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 6
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 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 6
- 238000001415 gene therapy Methods 0.000 description 6
- 241000958487 Adeno-associated virus 3B Species 0.000 description 5
- 108010027006 Apolipoproteins B Proteins 0.000 description 5
- 102000018616 Apolipoproteins B Human genes 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 5
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 5
- 108700026244 Open Reading Frames Proteins 0.000 description 5
- 241000701945 Parvoviridae Species 0.000 description 5
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 5
- 239000004473 Threonine Substances 0.000 description 5
- 238000010504 bond cleavage reaction Methods 0.000 description 5
- 229940088598 enzyme Drugs 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 5
- 210000002845 virion Anatomy 0.000 description 5
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 4
- 108020003589 5' Untranslated Regions Proteins 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 4
- 241000283707 Capra Species 0.000 description 4
- 102100034235 ELAV-like protein 1 Human genes 0.000 description 4
- 101150048357 Lamp1 gene Proteins 0.000 description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 4
- 102000006890 Methyl-CpG-Binding Protein 2 Human genes 0.000 description 4
- 210000001130 astrocyte Anatomy 0.000 description 4
- 238000001574 biopsy Methods 0.000 description 4
- 239000013592 cell lysate Substances 0.000 description 4
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 4
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 4
- 238000004806 packaging method and process Methods 0.000 description 4
- 230000014616 translation Effects 0.000 description 4
- 241000701161 unidentified adenovirus Species 0.000 description 4
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- 108010092674 Enkephalins Proteins 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- 229930186217 Glycolipid Natural products 0.000 description 3
- 102000002265 Human Growth Hormone Human genes 0.000 description 3
- 108010000521 Human Growth Hormone Proteins 0.000 description 3
- 239000000854 Human Growth Hormone Substances 0.000 description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
- 102100028251 Phosphoglycerate kinase 1 Human genes 0.000 description 3
- 101710139464 Phosphoglycerate kinase 1 Proteins 0.000 description 3
- 102000017975 Protein C Human genes 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Chemical compound CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- 230000035508 accumulation Effects 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 150000002305 glucosylceramides Chemical class 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 229930182817 methionine Natural products 0.000 description 3
- 230000000926 neurological effect Effects 0.000 description 3
- 210000004248 oligodendroglia Anatomy 0.000 description 3
- 229960000856 protein c Drugs 0.000 description 3
- 230000001603 reducing effect Effects 0.000 description 3
- 102200100757 rs62637007 Human genes 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- 108020005345 3' Untranslated Regions Proteins 0.000 description 2
- 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
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 2
- 101100495842 Caenorhabditis elegans cht-3 gene Proteins 0.000 description 2
- 101100222092 Caenorhabditis elegans csp-3 gene Proteins 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 101100285903 Drosophila melanogaster Hsc70-2 gene Proteins 0.000 description 2
- 101100178718 Drosophila melanogaster Hsc70-4 gene Proteins 0.000 description 2
- 101100178723 Drosophila melanogaster Hsc70-5 gene Proteins 0.000 description 2
- 102100031562 Excitatory amino acid transporter 2 Human genes 0.000 description 2
- 208000020322 Gaucher disease type I Diseases 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101150090950 Hsc70-1 gene Proteins 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 101710173130 Lysosomal acid glucosylceramidase Proteins 0.000 description 2
- 208000015439 Lysosomal storage disease Diseases 0.000 description 2
- 241000282567 Macaca fascicularis Species 0.000 description 2
- 241000282560 Macaca mulatta Species 0.000 description 2
- 101710107068 Myelin basic protein Proteins 0.000 description 2
- 241000125945 Protoparvovirus Species 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 102000017852 Saposin Human genes 0.000 description 2
- 108050007079 Saposin Proteins 0.000 description 2
- 101100150366 Schizosaccharomyces pombe (strain 972 / ATCC 24843) sks2 gene Proteins 0.000 description 2
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 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
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 230000021736 acetylation Effects 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 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 2
- 235000004279 alanine Nutrition 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 235000009582 asparagine Nutrition 0.000 description 2
- 229960001230 asparagine Drugs 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 210000003719 b-lymphocyte Anatomy 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000035605 chemotaxis Effects 0.000 description 2
- 238000012217 deletion Methods 0.000 description 2
- 230000037430 deletion Effects 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
- 230000006798 recombination Effects 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 102220231840 rs1064797305 Human genes 0.000 description 2
- 102200119083 rs118204039 Human genes 0.000 description 2
- 102220040801 rs140919432 Human genes 0.000 description 2
- 102220288338 rs1555548680 Human genes 0.000 description 2
- 102220071628 rs199472937 Human genes 0.000 description 2
- 102220014665 rs397517216 Human genes 0.000 description 2
- 102220035394 rs483352828 Human genes 0.000 description 2
- NEMGRZFTLSKBAP-LBPRGKRZSA-N safinamide Chemical compound C1=CC(CN[C@@H](C)C(N)=O)=CC=C1OCC1=CC=CC(F)=C1 NEMGRZFTLSKBAP-LBPRGKRZSA-N 0.000 description 2
- 229950002652 safinamide Drugs 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 210000004500 stellate cell Anatomy 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 239000004474 valine Substances 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
- MKSPBYRGLCNGRC-OEMOKZHXSA-N (2s)-2-[[(2s)-1-[(2s)-1-[(2s)-2-[[(2s)-2-[[(2s,3r)-2-[[(2s)-2-aminopropanoyl]amino]-3-hydroxybutanoyl]amino]-3-(1h-indol-3-yl)propanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound O=C([C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(=O)[C@H](C)N)[C@@H](C)O)CC(C)C)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O MKSPBYRGLCNGRC-OEMOKZHXSA-N 0.000 description 1
- SVONRAPFKPVNKG-UHFFFAOYSA-N 2-ethoxyethyl acetate Chemical compound CCOCCOC(C)=O SVONRAPFKPVNKG-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 241000425548 Adeno-associated virus 3A Species 0.000 description 1
- 102100034540 Adenomatous polyposis coli protein Human genes 0.000 description 1
- 102100026882 Alpha-synuclein Human genes 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 102000007592 Apolipoproteins Human genes 0.000 description 1
- 108010071619 Apolipoproteins Proteins 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 206010006542 Bulbar palsy Diseases 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- 101100495845 Caenorhabditis elegans cht-1 gene Proteins 0.000 description 1
- 101100441252 Caenorhabditis elegans csp-2 gene Proteins 0.000 description 1
- 101100043731 Caenorhabditis elegans syx-3 gene Proteins 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 102000004201 Ceramidases Human genes 0.000 description 1
- 108090000751 Ceramidases Proteins 0.000 description 1
- YBSQGNFRWZKFMJ-UHFFFAOYSA-N Cerebroside B Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(C(O)C=CCCC=C(C)CCCCCCCCC)COC1OC(CO)C(O)C(O)C1O YBSQGNFRWZKFMJ-UHFFFAOYSA-N 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
- 102000053602 DNA Human genes 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 102100035426 DnaJ homolog subfamily B member 7 Human genes 0.000 description 1
- 101100535673 Drosophila melanogaster Syn gene Proteins 0.000 description 1
- 108010053101 ELAV Proteins Proteins 0.000 description 1
- 102000016662 ELAV Proteins Human genes 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000032274 Encephalopathy Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108010000720 Excitatory Amino Acid Transporter 2 Proteins 0.000 description 1
- 102000001690 Factor VIII Human genes 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- 102220495209 Glutaredoxin-like protein C5orf63_T582S_mutation Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 101000924577 Homo sapiens Adenomatous polyposis coli protein Proteins 0.000 description 1
- 101001033280 Homo sapiens Cytokine receptor common subunit beta Proteins 0.000 description 1
- 101000804114 Homo sapiens DnaJ homolog subfamily B member 7 Proteins 0.000 description 1
- 101000866287 Homo sapiens Excitatory amino acid transporter 2 Proteins 0.000 description 1
- 101001050288 Homo sapiens Transcription factor Jun Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 description 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 description 1
- 108020005350 Initiator Codon Proteins 0.000 description 1
- 108010010994 K237 peptide Proteins 0.000 description 1
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
- ZFOMKMMPBOQKMC-KXUCPTDWSA-N L-pyrrolysine Chemical compound C[C@@H]1CC=N[C@H]1C(=O)NCCCC[C@H]([NH3+])C([O-])=O ZFOMKMMPBOQKMC-KXUCPTDWSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 239000004117 Lignosulphonate Substances 0.000 description 1
- 108010064171 Lysosome-Associated Membrane Glycoproteins Proteins 0.000 description 1
- 102000014944 Lysosome-Associated Membrane Glycoproteins Human genes 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 101100368134 Mus musculus Syn1 gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 208000002033 Myoclonus Diseases 0.000 description 1
- 102100032970 Myogenin Human genes 0.000 description 1
- 108010056785 Myogenin Proteins 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- 108010088373 Neurofilament Proteins Proteins 0.000 description 1
- 102000008763 Neurofilament Proteins Human genes 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 102100038931 Proenkephalin-A Human genes 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 208000008425 Protein deficiency Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108010005730 R-SNARE Proteins Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 239000004116 Sepiolitic clay Substances 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- 101000725126 Spinacia oleracea 50S ribosomal protein L35, chloroplastic Proteins 0.000 description 1
- 102000002215 Synaptobrevin Human genes 0.000 description 1
- 102000001317 Synaptotagmin I Human genes 0.000 description 1
- 108010055170 Synaptotagmin I Proteins 0.000 description 1
- 102000019355 Synuclein Human genes 0.000 description 1
- 108050006783 Synuclein Proteins 0.000 description 1
- 208000032859 Synucleinopathies Diseases 0.000 description 1
- 101001023030 Toxoplasma gondii Myosin-D Proteins 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 102100023132 Transcription factor Jun Human genes 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102100040247 Tumor necrosis factor Human genes 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 108091006088 activator proteins Proteins 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 102000013529 alpha-Fetoproteins Human genes 0.000 description 1
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 1
- 108090000185 alpha-Synuclein Proteins 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 210000000612 antigen-presenting cell Anatomy 0.000 description 1
- 108010048605 aspartyl-valyl-phenylalanyl-tyrosyl-prolyl-tyrosyl-prolyl-tyrosyl-alanyl-seryl-glycyl-serine Proteins 0.000 description 1
- 230000003140 astrocytic effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 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
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 102220419205 c.1712C>T Human genes 0.000 description 1
- 102220360931 c.3691A>G Human genes 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000000453 cell autonomous effect Effects 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 239000003636 conditioned culture medium Substances 0.000 description 1
- 210000000877 corpus callosum Anatomy 0.000 description 1
- 210000001653 corpus striatum Anatomy 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 108010066070 cysteinyl-prolyl-isoleucyl-glutamyl-aspartyl-arginyl-prolyl-methionyl-cysteine (1-9) disulfide Proteins 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 231100000020 developmental retardation Toxicity 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- FJZZPCZKBUKGGU-AUSIDOKSSA-N eliglustat Chemical compound C([C@@H](NC(=O)CCCCCCC)[C@H](O)C=1C=C2OCCOC2=CC=1)N1CCCC1 FJZZPCZKBUKGGU-AUSIDOKSSA-N 0.000 description 1
- 229960002856 eliglustat Drugs 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 230000004424 eye movement Effects 0.000 description 1
- 229960000301 factor viii Drugs 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000007614 genetic variation Effects 0.000 description 1
- 150000002339 glycosphingolipids Chemical class 0.000 description 1
- 210000002064 heart cell Anatomy 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 108010046019 histidyl-glutamyl-tryptophyl-seryl-tyrosyl-leucyl-alanyl-prolyl-tyrosyl-prolyl-tryptophyl-phenylalanine Proteins 0.000 description 1
- 102000055647 human CSF2RB Human genes 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 108010039650 imiglucerase Proteins 0.000 description 1
- 229960002127 imiglucerase Drugs 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
- 210000004558 lewy body Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 208000014416 lysosomal lipid storage disease Diseases 0.000 description 1
- 108010045758 lysosomal proteins Proteins 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- 238000009126 molecular therapy Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 210000005044 neurofilament Anatomy 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 230000001124 posttranscriptional effect Effects 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 108010041071 proenkephalin Proteins 0.000 description 1
- 201000002241 progressive bulbar palsy Diseases 0.000 description 1
- 210000004777 protein coat Anatomy 0.000 description 1
- 230000020978 protein processing Effects 0.000 description 1
- 210000002637 putamen Anatomy 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 102220033742 rs104886487 Human genes 0.000 description 1
- 102220198256 rs1057519940 Human genes 0.000 description 1
- 102200017383 rs121918379 Human genes 0.000 description 1
- 102220003569 rs137852596 Human genes 0.000 description 1
- 102220260129 rs1554011822 Human genes 0.000 description 1
- 102220300987 rs1554081754 Human genes 0.000 description 1
- 102200163429 rs369088781 Human genes 0.000 description 1
- 102220135453 rs369488860 Human genes 0.000 description 1
- 102220240190 rs375064450 Human genes 0.000 description 1
- 102220129048 rs376402047 Human genes 0.000 description 1
- 102220039319 rs587780542 Human genes 0.000 description 1
- 102220233554 rs761858047 Human genes 0.000 description 1
- 102220096219 rs876659201 Human genes 0.000 description 1
- 102220105951 rs879254931 Human genes 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
- 230000009870 specific binding Effects 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 108060008004 synaptotagmin Proteins 0.000 description 1
- 102000003137 synaptotagmin Human genes 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 108010072309 taliglucerase alfa Proteins 0.000 description 1
- 229960001832 taliglucerase alfa Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 239000012581 transferrin Substances 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 229940035893 uracil Drugs 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
- 239000003981 vehicle Substances 0.000 description 1
- 229960004406 velaglucerase alfa Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/12—Viral antigens
- A61K39/235—Adenoviridae
-
- 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
-
- 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
- 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
-
- 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)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- Psychiatry (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Hospice & Palliative Care (AREA)
- Plant Pathology (AREA)
- Psychology (AREA)
- Mycology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202063057265P | 2020-07-27 | 2020-07-27 | |
| US63/057,265 | 2020-07-27 | ||
| PCT/US2021/043216 WO2022026409A1 (en) | 2020-07-27 | 2021-07-26 | Compositions and methods for the treatment of neurological disorders related to glucosylceramidase beta deficiency |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117120619A true CN117120619A (zh) | 2023-11-24 |
Family
ID=77338944
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202180066205.8A Pending CN117120619A (zh) | 2020-07-27 | 2021-07-26 | 用于治疗与葡萄糖神经酰胺酶β缺陷相关的神经病症的组合物和方法 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20230227802A1 (https=) |
| EP (1) | EP4189095A1 (https=) |
| JP (1) | JP2023536091A (https=) |
| KR (1) | KR20230093241A (https=) |
| CN (1) | CN117120619A (https=) |
| AU (1) | AU2021315876A1 (https=) |
| BR (1) | BR112023001456A2 (https=) |
| CA (1) | CA3190309A1 (https=) |
| IL (1) | IL299928A (https=) |
| MX (1) | MX2023000815A (https=) |
| TW (1) | TW202221125A (https=) |
| WO (1) | WO2022026409A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118064436A (zh) * | 2024-04-18 | 2024-05-24 | 上海凌医生物科技有限公司 | 一种增强基因表达的嵌合启动子 |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20250049955A1 (en) | 2021-11-17 | 2025-02-13 | Voyager Therapeutics, Inc. | Compositons and methods for the treatment of neurological disorders related to glucosylceramidase beta deficiency |
| WO2023215851A2 (en) * | 2022-05-06 | 2023-11-09 | Apic Bio, Inc. | Plasmid optimized for packaging of aav vectors |
| AU2023427408A1 (en) * | 2023-02-02 | 2025-09-04 | Voyager Therapeutics, Inc. | Compositions and methods for the treatment of neurological disorders related to glucosylceramidase beta deficiency |
| WO2024226761A2 (en) * | 2023-04-26 | 2024-10-31 | Voyager Therapeutics, Inc. | Compositions and methods for treating amyotrophic lateral sclerosis |
| WO2024226790A1 (en) * | 2023-04-26 | 2024-10-31 | Voyager Therapeutics, Inc. | Aav capsid variants and uses thereof |
| WO2025039622A1 (zh) * | 2023-08-23 | 2025-02-27 | 上海金珂博生物技术有限公司 | 经修饰的腺相关病毒载体及其在治疗中枢神经系统疾病中的用途 |
| CN117264912A (zh) * | 2023-09-25 | 2023-12-22 | 中国科学院深圳先进技术研究院 | 一种重组腺相关病毒颗粒、重组腺相关病毒载体系统及其应用 |
| CN121518479B (zh) * | 2026-01-16 | 2026-04-24 | 凌意(杭州)生物科技有限公司 | 基因编辑复合型突变小鼠模型的构建方法 |
Family Cites Families (94)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US5173414A (en) | 1990-10-30 | 1992-12-22 | Applied Immune Sciences, Inc. | Production of recombinant adeno-associated virus vectors |
| US5525491A (en) | 1991-02-27 | 1996-06-11 | Creative Biomolecules, Inc. | Serine-rich peptide linkers |
| US5387484A (en) | 1992-07-07 | 1995-02-07 | International Business Machines Corporation | Two-sided mask for patterning of materials with electromagnetic radiation |
| WO1994012520A1 (en) | 1992-11-20 | 1994-06-09 | Enzon, Inc. | Linker for linked fusion polypeptides |
| ATE386131T1 (de) | 1994-04-13 | 2008-03-15 | Univ Rockefeller | Aav-vermittelte überbringung von dna in zellen des nervensystems |
| US6204059B1 (en) | 1994-06-30 | 2001-03-20 | University Of Pittsburgh | AAV capsid vehicles for molecular transfer |
| US5625048A (en) | 1994-11-10 | 1997-04-29 | The Regents Of The University Of California | Modified green fluorescent proteins |
| CA2207927A1 (en) | 1994-12-06 | 1996-06-13 | Targeted Genetics Corporation | Packaging cell lines for generation of high titers of recombinant aav vectors |
| US5741657A (en) | 1995-03-20 | 1998-04-21 | The Regents Of The University Of California | Fluorogenic substrates for β-lactamase and methods of use |
| US6281010B1 (en) | 1995-06-05 | 2001-08-28 | The Trustees Of The University Of Pennsylvania | Adenovirus gene therapy vehicle and cell line |
| US5688676A (en) | 1995-06-07 | 1997-11-18 | Research Foundation Of State University Of New York | In vitro packaging of adeno-associated virus DNA |
| US5741683A (en) | 1995-06-07 | 1998-04-21 | The Research Foundation Of State University Of New York | In vitro packaging of adeno-associated virus DNA |
| US6265389B1 (en) | 1995-08-31 | 2001-07-24 | Alkermes Controlled Therapeutics, Inc. | Microencapsulation and sustained release of oligonucleotides |
| US5858351A (en) | 1996-01-18 | 1999-01-12 | Avigen, Inc. | Methods for delivering DNA to muscle cells using recombinant adeno-associated virus vectors |
| US5962313A (en) | 1996-01-18 | 1999-10-05 | Avigen, Inc. | Adeno-associated virus vectors comprising a gene encoding a lyosomal enzyme |
| US5846528A (en) | 1996-01-18 | 1998-12-08 | Avigen, Inc. | Treating anemia using recombinant adeno-associated virus virions comprising an EPO DNA sequence |
| AU722375B2 (en) | 1996-09-06 | 2000-08-03 | Trustees Of The University Of Pennsylvania, The | Methods using cre-lox for production of recombinant adeno-associated viruses |
| WO1998011244A2 (en) | 1996-09-11 | 1998-03-19 | The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Aav4 vector and uses thereof |
| JP2001506133A (ja) | 1996-12-18 | 2001-05-15 | ターゲティッド ジェネティクス コーポレイション | 組換えaavベクターの産生における使用のための、aavスプリット−パッケージング遺伝子およびこのような遺伝子を含む細胞株 |
| NZ333334A (en) | 1997-04-17 | 2001-06-29 | Frank L Sorgi | Delivery system for gene therapy to the brain |
| US6156303A (en) | 1997-06-11 | 2000-12-05 | University Of Washington | Adeno-associated virus (AAV) isolates and AAV vectors derived therefrom |
| EP1124976A1 (en) | 1998-10-27 | 2001-08-22 | Crucell Holland B.V. | Improved aav vector production |
| AU780231B2 (en) | 1998-11-10 | 2005-03-10 | University Of North Carolina At Chapel Hill, The | Virus vectors and methods of making and administering the same |
| US6225113B1 (en) | 1998-12-04 | 2001-05-01 | Genvec, Inc. | Use of trans-activation and cis-activation to modulate the persistence of expression of a transgene in an at least E4-deficient adenovirus |
| DE19905501B4 (de) | 1999-02-10 | 2005-05-19 | MediGene AG, Gesellschaft für molekularbiologische Kardiologie und Onkologie | Verfahren zur Herstellung eines rekombinanten Adeno-assoziierten Virus, geeignete Mittel hierzu sowie Verwendung zur Herstellung eines Arzneimittels |
| JP2003523320A (ja) | 1999-09-29 | 2003-08-05 | ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア | ウイルスベクターの迅速なpeg改変方法、高められた遺伝子形質導入のための組成物、高められた物理的安定性を伴う組成物、およびそのための用途 |
| US6365394B1 (en) | 1999-09-29 | 2002-04-02 | The Trustees Of The University Of Pennsylvania | Cell lines and constructs useful in production of E1-deleted adenoviruses in absence of replication competent adenovirus |
| CA2409674C (en) | 2000-05-23 | 2010-05-11 | Neurologix, Inc. | Glutamic acid decarboxylase (gad) based delivery systems |
| ATE318923T1 (de) | 2000-06-01 | 2006-03-15 | Univ North Carolina | Doppelsträngige parvovirus-vektoren |
| WO2001096587A2 (en) | 2000-06-13 | 2001-12-20 | The Children's Hospital Of Philadelphia | Methods for administering recombinant adeno-associated virus virions to humans previously exposed to adeno-associated virus |
| DE60129229T2 (de) | 2000-08-17 | 2008-05-08 | Ozawa, Keiya | Adeno-assoziierte virus-vermittelte übertragung von angiogenesefaktoren |
| US7588757B2 (en) | 2001-03-14 | 2009-09-15 | Genzyme Corporation | Methods of treating Parkinson's disease using recombinant adeno-associated virus virions |
| MX359371B (es) | 2001-11-13 | 2018-09-25 | Univ Pennsylvania | Un metodo para detectar y/o identificar secuencias del virus adeno-asociado y aislamiento de secuencias novedosas identificadas de ese modo. |
| DK2573170T3 (en) | 2001-12-17 | 2018-04-09 | Univ Pennsylvania | Sequences of adeno-associated virus (AAV) serotype 9, vectors containing them, and their use |
| EP1463530A4 (en) | 2001-12-19 | 2006-09-06 | Lijun Wang | ADENO-ASSOCIATED VIRUS-RELATED DELIVERY OF GDNF TO SKELETAL MUSCLES |
| US8946151B2 (en) | 2003-02-24 | 2015-02-03 | Northern Bristol N.H.S. Trust Frenchay Hospital | Method of treating Parkinson's disease in humans by convection-enhanced infusion of glial cell-line derived neurotrophic factor to the putamen |
| US7951557B2 (en) | 2003-04-27 | 2011-05-31 | Protalix Ltd. | Human lysosomal proteins from plant cell culture |
| US8927269B2 (en) | 2003-05-19 | 2015-01-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Avian adenoassociated virus and uses thereof |
| JP4888876B2 (ja) | 2003-06-13 | 2012-02-29 | 田平 武 | アルツハイマー病の治療のための組換えアデノ随伴ウィルスベクター |
| SI1633772T1 (sl) | 2003-06-19 | 2016-06-30 | Genzyme Corporation | AAV virioni z zmanjšano imunoreaktivnostjo in uporaba za ta namen |
| US9233131B2 (en) | 2003-06-30 | 2016-01-12 | The Regents Of The University Of California | Mutant adeno-associated virus virions and methods of use thereof |
| US9441244B2 (en) | 2003-06-30 | 2016-09-13 | The Regents Of The University Of California | Mutant adeno-associated virus virions and methods of use thereof |
| EP2345731B1 (en) | 2003-09-30 | 2015-10-21 | The Trustees of the University of Pennsylvania | Adeno-associated virus (AAV) clades, sequences, vectors containing same, and uses thereof |
| US8137960B2 (en) | 2003-12-04 | 2012-03-20 | The United States Of America As Represented By The Department Of Health And Human Services | Bovine adeno-associated viral (BAAV) vector and uses thereof |
| US20060166363A1 (en) | 2004-01-27 | 2006-07-27 | Sergei Zolotukhin | Modified baculovirus expression system for production of pseudotyped rAAV vector |
| US7427396B2 (en) | 2004-06-03 | 2008-09-23 | Genzyme Corporation | AAV vectors for gene delivery to the lung |
| ES2525067T3 (es) | 2005-04-07 | 2014-12-17 | The Trustees Of The University Of Pennsylvania | Método de incremento de la función de un vector de AAV |
| WO2006119432A2 (en) | 2005-04-29 | 2006-11-09 | The Government Of The U.S.A., As Rep. By The Sec., Dept. Of Health & Human Services | Isolation, cloning and characterization of new adeno-associated virus (aav) serotypes |
| EP1857552A1 (en) | 2006-05-20 | 2007-11-21 | Cargill Incorporated | Thermostable xylose isomerase enzyme |
| EP2311966A3 (en) | 2005-10-20 | 2012-09-05 | Amsterdam Molecular Therapeutics (AMT) B.V. | Improved AAV vectors produced in insect cells |
| US7588772B2 (en) | 2006-03-30 | 2009-09-15 | Board Of Trustees Of The Leland Stamford Junior University | AAV capsid library and AAV capsid proteins |
| CN103849629B (zh) | 2006-06-21 | 2017-06-09 | 尤尼克尔Ip股份有限公司 | 具有经修饰的用于在昆虫细胞中产生aav的aav‑rep78翻译起始密码子的载体 |
| EP2079840A4 (en) | 2006-10-30 | 2010-06-30 | Viventia Biotech Inc | IMMUNOTOXIN FUSIONS COMPRISING PROTEASEPLATABLE LINKER-ASSOCIATED ANTIBODY FRAGMENT AND PLANT TOXIN |
| ES2602610T3 (es) | 2007-05-31 | 2017-02-21 | Medigene Ag | Proteína estructural mutada de un parvovirus |
| DK2173888T3 (en) | 2007-07-26 | 2016-11-28 | Uniqure Ip Bv | Baculovirus vectors comprising repeating coding sequences WITH differential preferred codons |
| WO2010093784A2 (en) | 2009-02-11 | 2010-08-19 | The University Of North Carolina At Chapel Hill | Modified virus vectors and methods of making and using the same |
| US8734809B2 (en) | 2009-05-28 | 2014-05-27 | University Of Massachusetts | AAV's and uses thereof |
| US9163261B2 (en) | 2010-02-22 | 2015-10-20 | Koteswara Rao KOLLIPARA | Adeno-associated virus 2/8—micro RNA-101 therapy for liver cancer |
| EP2394667A1 (en) | 2010-06-10 | 2011-12-14 | Laboratorios Del Dr. Esteve, S.A. | Vectors and sequences for the treatment of diseases |
| WO2012057363A1 (ja) | 2010-10-27 | 2012-05-03 | 学校法人自治医科大学 | 神経系細胞への遺伝子導入のためのアデノ随伴ウイルスビリオン |
| US8865881B2 (en) | 2011-02-22 | 2014-10-21 | California Institute Of Technology | Delivery of proteins using adeno-associated virus (AAV) vectors |
| CN103476399A (zh) | 2011-04-18 | 2013-12-25 | 独立行政法人国立精神·神经医疗研究中心 | 药剂递送粒子及其制造方法 |
| ES2857773T5 (es) | 2011-08-24 | 2024-06-04 | Univ Leland Stanford Junior | Nuevas proteínas de la cápside de AAV para la transferencia de ácidos nucleicos |
| US20140359799A1 (en) | 2011-12-23 | 2014-12-04 | Case Western Reserve University | Targeted gene modification using hybrid recombinant adeno-associated virus |
| CN104411338A (zh) * | 2012-04-02 | 2015-03-11 | 现代治疗公司 | 用于产生与人类疾病相关的生物制剂和蛋白质的修饰多核苷酸 |
| WO2013151665A2 (en) * | 2012-04-02 | 2013-10-10 | modeRNA Therapeutics | Modified polynucleotides for the production of proteins associated with human disease |
| EP2900686B1 (en) | 2012-09-28 | 2020-06-10 | The University of North Carolina At Chapel Hill | Aav vectors targeted to oligodendrocytes |
| US9567376B2 (en) | 2013-02-08 | 2017-02-14 | The Trustees Of The University Of Pennsylvania | Enhanced AAV-mediated gene transfer for retinal therapies |
| ES2926774T3 (es) | 2013-03-15 | 2022-10-28 | Univ North Carolina Chapel Hill | Métodos y composiciones para vectores AAV de doble unión de glicano |
| MX380973B (es) | 2013-05-01 | 2025-03-12 | Genzyme Corp | Composiciones y metodos para tratar la atrofia muscular espinal. |
| EP3003391B1 (en) | 2013-05-31 | 2021-09-22 | The Regents of The University of California | Adeno-associated virus variants and methods of use thereof |
| ES2739288T3 (es) | 2013-09-13 | 2020-01-30 | California Inst Of Techn | Recuperación selectiva |
| WO2015048534A1 (en) | 2013-09-26 | 2015-04-02 | University Of Florida Research Foundation, Inc. | Synthetic combinatorial aav capsid library for targeted gene therapy |
| US10087224B2 (en) | 2013-11-01 | 2018-10-02 | Cornell University | Gene therapy for Alzheimer's and other neurodegenerative diseases and conditions |
| GB201403684D0 (en) | 2014-03-03 | 2014-04-16 | King S College London | Vector |
| LT3137497T (lt) | 2014-05-02 | 2021-07-26 | Genzyme Corporation | Aav vektoriai, skirti tinklainės ir cns genų terapijai |
| EP3151866B1 (en) | 2014-06-09 | 2023-03-08 | Voyager Therapeutics, Inc. | Chimeric capsids |
| AU2015320694B2 (en) | 2014-09-24 | 2021-11-11 | City Of Hope | Adeno-associated virus vector variants for high efficiency genome editing and methods thereof |
| CN107073051B (zh) | 2014-10-21 | 2021-08-24 | 马萨诸塞大学 | 重组aav变体及其用途 |
| AU2016219789B2 (en) | 2015-02-20 | 2021-03-25 | Fondazione Telethon | Methods and compositions for treating genetic eye diseases |
| WO2017015102A1 (en) | 2015-07-17 | 2017-01-26 | The Trustees Of The University Of Pennsylvania | Compositions and methods for achieving high levels of transduction in human liver cells |
| ES2865487T3 (es) | 2015-09-28 | 2021-10-15 | Univ North Carolina Chapel Hill | Métodos y composiciones para vectores virales que evaden los anticuerpos |
| WO2017066764A2 (en) | 2015-10-16 | 2017-04-20 | William Marsh Rice University | Modification of n-terminal region of capsid proteins for enhanced properties of adeno-associated viruses |
| WO2017083722A1 (en) | 2015-11-11 | 2017-05-18 | Greenberg Kenneth P | Crispr compositions and methods of using the same for gene therapy |
| US10240145B2 (en) | 2015-11-25 | 2019-03-26 | The Board Of Trustees Of The Leland Stanford Junior University | CRISPR/Cas-mediated genome editing to treat EGFR-mutant lung cancer |
| KR102423442B1 (ko) | 2015-12-11 | 2022-07-20 | 캘리포니아 인스티튜트 오브 테크놀로지 | 아데노-관련 바이러스를 지시하기 위한 타겟팅 펩타이드 |
| BR112020006661A2 (pt) * | 2017-10-03 | 2020-10-13 | Prevail Therapeutics, Inc. | terapias de genes para distúrbios lipossomais |
| AU2018346104B2 (en) | 2017-10-03 | 2023-07-27 | Prevail Therapeutics, Inc. | Gene therapies for lysosomal disorders |
| WO2019136484A1 (en) | 2018-01-08 | 2019-07-11 | Prevail Therapeutics, Inc. | Pet imaging ligands for in vivo detection of gba1 |
| JP2021517168A (ja) * | 2018-03-09 | 2021-07-15 | アブロバイオ,インコーポレーテッド | パーキンソン病を処置するための組成物及び方法 |
| BR112020021962A2 (pt) | 2018-04-30 | 2021-01-26 | Amicus Therapeutics, Inc. | construtos para terapia gênica e métodos de uso |
| US20210214749A1 (en) * | 2018-05-16 | 2021-07-15 | Voyager Therapeutics, Inc. | Directed evolution |
| WO2020132455A1 (en) | 2018-12-21 | 2020-06-25 | The Trustees Of The University Of Pennsylvania | Compositions for drg-specific reduction of transgene expression |
-
2021
- 2021-07-26 BR BR112023001456A patent/BR112023001456A2/pt unknown
- 2021-07-26 EP EP21755300.7A patent/EP4189095A1/en active Pending
- 2021-07-26 MX MX2023000815A patent/MX2023000815A/es unknown
- 2021-07-26 AU AU2021315876A patent/AU2021315876A1/en active Pending
- 2021-07-26 JP JP2023505751A patent/JP2023536091A/ja active Pending
- 2021-07-26 CN CN202180066205.8A patent/CN117120619A/zh active Pending
- 2021-07-26 KR KR1020237006825A patent/KR20230093241A/ko active Pending
- 2021-07-26 US US18/018,017 patent/US20230227802A1/en active Pending
- 2021-07-26 WO PCT/US2021/043216 patent/WO2022026409A1/en not_active Ceased
- 2021-07-26 TW TW110127422A patent/TW202221125A/zh unknown
- 2021-07-26 IL IL299928A patent/IL299928A/en unknown
- 2021-07-26 CA CA3190309A patent/CA3190309A1/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118064436A (zh) * | 2024-04-18 | 2024-05-24 | 上海凌医生物科技有限公司 | 一种增强基因表达的嵌合启动子 |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20230093241A (ko) | 2023-06-27 |
| US20230227802A1 (en) | 2023-07-20 |
| CA3190309A1 (en) | 2022-02-03 |
| JP2023536091A (ja) | 2023-08-23 |
| WO2022026409A1 (en) | 2022-02-03 |
| TW202221125A (zh) | 2022-06-01 |
| BR112023001456A2 (pt) | 2023-04-11 |
| EP4189095A1 (en) | 2023-06-07 |
| MX2023000815A (es) | 2023-04-11 |
| IL299928A (en) | 2023-03-01 |
| AU2021315876A1 (en) | 2023-02-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7761686B2 (ja) | 操作されたプロモータを有するフラタキシン発現コンストラクトおよびその使用方法 | |
| US20240131093A1 (en) | Compositions and methods of treating huntington's disease | |
| CN117120619A (zh) | 用于治疗与葡萄糖神经酰胺酶β缺陷相关的神经病症的组合物和方法 | |
| JP7221275B2 (ja) | Aavを送達するための組成物および方法 | |
| US20220333131A1 (en) | Modulatory polynucleotides | |
| US20250049955A1 (en) | Compositons and methods for the treatment of neurological disorders related to glucosylceramidase beta deficiency | |
| US20220275367A1 (en) | Compositions and methods for treating huntington's disease | |
| US20230285596A1 (en) | Compositions and methods for the treatment of niemann-pick type c1 disease | |
| CN118475699A (zh) | 包含嗜肝衣壳蛋白和α-半乳糖苷酶的AAV颗粒及其治疗法布里病的用途 | |
| TWI813851B (zh) | 具有工程化之啟動子之共濟蛋白(frataxin)表現構築體及其使用方法 | |
| JP2026071207A (ja) | グルコシルセラミダーゼベータ欠損に関連する神経障害の治療のための組成物及び方法 | |
| TW202449149A (zh) | 用於治療與葡萄糖神經醯胺酶β1缺陷相關之神經病症的組合物及方法 | |
| HK40101579A (zh) | 用於治疗与葡萄糖神经酰胺酶β缺陷相关的神经病症的组合物和方法 | |
| HK40061110A (zh) | 具有经工程化改造的启动子的共济蛋白表达构建体及其使用方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 40101579 Country of ref document: HK |