TW202027781A - 雙硫鍵穩定化之多肽組合物及使用方法 - Google Patents
雙硫鍵穩定化之多肽組合物及使用方法 Download PDFInfo
- Publication number
- TW202027781A TW202027781A TW108136956A TW108136956A TW202027781A TW 202027781 A TW202027781 A TW 202027781A TW 108136956 A TW108136956 A TW 108136956A TW 108136956 A TW108136956 A TW 108136956A TW 202027781 A TW202027781 A TW 202027781A
- Authority
- TW
- Taiwan
- Prior art keywords
- disease
- type
- polypeptide
- gal
- protein
- Prior art date
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 541
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 509
- 229920001184 polypeptide Polymers 0.000 title claims abstract description 503
- 238000000034 method Methods 0.000 title claims description 76
- 239000000203 mixture Substances 0.000 title description 22
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 197
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims abstract description 175
- 235000018102 proteins Nutrition 0.000 claims abstract description 144
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 144
- 235000018417 cysteine Nutrition 0.000 claims abstract description 133
- 238000001415 gene therapy Methods 0.000 claims abstract description 105
- 208000026350 Inborn Genetic disease Diseases 0.000 claims abstract description 51
- 208000016361 genetic disease Diseases 0.000 claims abstract description 51
- 238000011282 treatment Methods 0.000 claims abstract description 29
- 239000000178 monomer Substances 0.000 claims abstract description 10
- NNISLDGFPWIBDF-MPRBLYSKSA-N alpha-D-Gal-(1->3)-beta-D-Gal-(1->4)-D-GlcNAc Chemical compound O[C@@H]1[C@@H](NC(=O)C)C(O)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@@H](CO)O1 NNISLDGFPWIBDF-MPRBLYSKSA-N 0.000 claims description 348
- 101000718529 Saccharolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2) Alpha-galactosidase Proteins 0.000 claims description 280
- 150000007523 nucleic acids Chemical class 0.000 claims description 239
- 108020002591 Palmitoyl protein thioesterase Proteins 0.000 claims description 186
- 102000005327 Palmitoyl protein thioesterase Human genes 0.000 claims description 185
- 102000039446 nucleic acids Human genes 0.000 claims description 153
- 108020004707 nucleic acids Proteins 0.000 claims description 153
- 239000013598 vector Substances 0.000 claims description 153
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 148
- 201000010099 disease Diseases 0.000 claims description 146
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 110
- 230000002981 neuropathic effect Effects 0.000 claims description 83
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 81
- 101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 claims description 57
- 239000008194 pharmaceutical composition Substances 0.000 claims description 40
- 208000024891 symptom Diseases 0.000 claims description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 37
- 238000003860 storage Methods 0.000 claims description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 claims description 30
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 30
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 30
- 241000700605 Viruses Species 0.000 claims description 30
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 30
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 27
- 102100026277 Alpha-galactosidase A Human genes 0.000 claims description 26
- 241000702421 Dependoparvovirus Species 0.000 claims description 25
- 208000024720 Fabry Disease Diseases 0.000 claims description 25
- 102000004190 Enzymes Human genes 0.000 claims description 23
- 108090000790 Enzymes Proteins 0.000 claims description 23
- 229940088598 enzyme Drugs 0.000 claims description 23
- 150000001945 cysteines Chemical class 0.000 claims description 21
- 101000718525 Homo sapiens Alpha-galactosidase A Proteins 0.000 claims description 20
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 20
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 20
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 20
- 239000011780 sodium chloride Substances 0.000 claims description 20
- 235000002639 sodium chloride Nutrition 0.000 claims description 20
- 241000701161 unidentified adenovirus Species 0.000 claims description 20
- 239000013603 viral vector Substances 0.000 claims description 20
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 20
- 241001430294 unidentified retrovirus Species 0.000 claims description 19
- 241000713666 Lentivirus Species 0.000 claims description 17
- 108010030291 alpha-Galactosidase Proteins 0.000 claims description 17
- 241001529453 unidentified herpesvirus Species 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 229910001868 water Inorganic materials 0.000 claims description 17
- 208000029602 Alpha-N-acetylgalactosaminidase deficiency Diseases 0.000 claims description 16
- 102100025621 Cytochrome b-245 heavy chain Human genes 0.000 claims description 16
- 108010017544 Glucosylceramidase Proteins 0.000 claims description 16
- 102000004547 Glucosylceramidase Human genes 0.000 claims description 16
- 229920002683 Glycosaminoglycan Polymers 0.000 claims description 16
- 102000004627 Iduronidase Human genes 0.000 claims description 16
- 108010003381 Iduronidase Proteins 0.000 claims description 16
- 102100025947 Insulin-like growth factor II Human genes 0.000 claims description 16
- 108010006140 N-sulfoglucosamine sulfohydrolase Proteins 0.000 claims description 16
- 102100027661 N-sulphoglucosamine sulphohydrolase Human genes 0.000 claims description 16
- 108010039203 Tripeptidyl-Peptidase 1 Proteins 0.000 claims description 16
- 102100034197 Tripeptidyl-peptidase 1 Human genes 0.000 claims description 16
- 208000016532 chronic granulomatous disease Diseases 0.000 claims description 16
- 108700001567 Type I Schindler Disease Proteins 0.000 claims description 15
- 102100034746 Cyclin-dependent kinase-like 5 Human genes 0.000 claims description 13
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 claims description 13
- 238000007913 intrathecal administration Methods 0.000 claims description 12
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 10
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 10
- 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 claims description 10
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 10
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 10
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 10
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 10
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 10
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 10
- 235000011054 acetic acid Nutrition 0.000 claims description 10
- 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 claims description 10
- 239000001110 calcium chloride Substances 0.000 claims description 10
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 10
- 235000011148 calcium chloride Nutrition 0.000 claims description 10
- 235000015165 citric acid Nutrition 0.000 claims description 10
- 239000008121 dextrose Substances 0.000 claims description 10
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 claims description 10
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 claims description 10
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 10
- 235000014304 histidine Nutrition 0.000 claims description 10
- 239000004310 lactic acid Substances 0.000 claims description 10
- 235000014655 lactic acid Nutrition 0.000 claims description 10
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 10
- 239000011976 maleic acid Substances 0.000 claims description 10
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 10
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 10
- 229920000053 polysorbate 80 Polymers 0.000 claims description 10
- 239000001103 potassium chloride Substances 0.000 claims description 10
- 235000011164 potassium chloride Nutrition 0.000 claims description 10
- 239000001488 sodium phosphate Substances 0.000 claims description 10
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 10
- 235000011008 sodium phosphates Nutrition 0.000 claims description 10
- 239000004094 surface-active agent Substances 0.000 claims description 10
- 239000011975 tartaric acid Substances 0.000 claims description 10
- 235000002906 tartaric acid Nutrition 0.000 claims description 10
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 10
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 10
- 239000011592 zinc chloride Substances 0.000 claims description 10
- 235000005074 zinc chloride Nutrition 0.000 claims description 10
- 208000015439 Lysosomal storage disease Diseases 0.000 claims description 9
- 238000010253 intravenous injection Methods 0.000 claims description 9
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 claims description 8
- 102000055025 Adenosine deaminases Human genes 0.000 claims description 8
- 206010011777 Cystinosis Diseases 0.000 claims description 8
- 208000020322 Gaucher disease type I Diseases 0.000 claims description 8
- 208000028735 Gaucher disease type III Diseases 0.000 claims description 8
- 206010053185 Glycogen storage disease type II Diseases 0.000 claims description 8
- 101000945692 Homo sapiens Cyclin-dependent kinase-like 5 Proteins 0.000 claims description 8
- 102100026001 Lysosomal acid lipase/cholesteryl ester hydrolase Human genes 0.000 claims description 8
- 201000011442 Metachromatic leukodystrophy Diseases 0.000 claims description 8
- 102100031688 N-acetylgalactosamine-6-sulfatase Human genes 0.000 claims description 8
- 101710099863 N-acetylgalactosamine-6-sulfatase Proteins 0.000 claims description 8
- 108010055297 Sterol Esterase Proteins 0.000 claims description 8
- 108010028144 alpha-Glucosidases Proteins 0.000 claims description 8
- 230000007812 deficiency Effects 0.000 claims description 8
- 230000002950 deficient Effects 0.000 claims description 8
- 201000004502 glycogen storage disease II Diseases 0.000 claims description 8
- 208000002491 severe combined immunodeficiency Diseases 0.000 claims description 8
- 241000702423 Adeno-associated virus - 2 Species 0.000 claims description 7
- 102100031491 Arylsulfatase B Human genes 0.000 claims description 7
- 108010027520 N-Acetylgalactosamine-4-Sulfatase Proteins 0.000 claims description 7
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 claims description 7
- 208000012902 Nervous system disease Diseases 0.000 claims description 7
- 238000007914 intraventricular administration Methods 0.000 claims description 7
- 208000011045 mucopolysaccharidosis type 3 Diseases 0.000 claims description 7
- 101000574223 Homo sapiens Palmitoyl-protein thioesterase 1 Proteins 0.000 claims description 6
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 102000043404 human GLA Human genes 0.000 claims description 6
- 230000000926 neurological effect Effects 0.000 claims description 6
- 101710178912 Cyclin-dependent kinase-like 5 Proteins 0.000 claims description 5
- 208000020916 Gaucher disease type II Diseases 0.000 claims description 5
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 claims description 5
- 208000025797 Mucopolysaccharidosis type 4A Diseases 0.000 claims description 5
- 208000008291 Type B Niemann-Pick Disease Diseases 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 102000051672 human PPT1 Human genes 0.000 claims description 5
- 238000007918 intramuscular administration Methods 0.000 claims description 5
- 230000001272 neurogenic effect Effects 0.000 claims description 5
- 238000007920 subcutaneous administration Methods 0.000 claims description 5
- 108010011485 Aspartame Proteins 0.000 claims description 4
- 102100028215 BTB/POZ domain-containing protein KCTD7 Human genes 0.000 claims description 4
- 208000033418 CLN1 disease Diseases 0.000 claims description 4
- 101001007222 Homo sapiens BTB/POZ domain-containing protein KCTD7 Proteins 0.000 claims description 4
- 101000625846 Homo sapiens TBC domain-containing protein kinase-like protein Proteins 0.000 claims description 4
- 208000025915 Mucopolysaccharidosis type 6 Diseases 0.000 claims description 4
- 201000000788 Niemann-Pick disease type C1 Diseases 0.000 claims description 4
- 201000000785 Niemann-Pick disease type C2 Diseases 0.000 claims description 4
- 102000019204 Progranulins Human genes 0.000 claims description 4
- 108010012809 Progranulins Proteins 0.000 claims description 4
- 102100024750 TBC domain-containing protein kinase-like protein Human genes 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 102000005840 alpha-Galactosidase Human genes 0.000 claims description 4
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical group OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 4
- 239000000605 aspartame Substances 0.000 claims description 4
- 229960003438 aspartame Drugs 0.000 claims description 4
- 235000010357 aspartame Nutrition 0.000 claims description 4
- 230000002132 lysosomal effect Effects 0.000 claims description 4
- 201000007642 neuronal ceroid lipofuscinosis 1 Diseases 0.000 claims description 4
- 230000008488 polyadenylation Effects 0.000 claims description 4
- 208000035343 Infantile neurovisceral acid sphingomyelinase deficiency Diseases 0.000 claims description 3
- 206010028095 Mucopolysaccharidosis IV Diseases 0.000 claims description 3
- 206010056893 Mucopolysaccharidosis VII Diseases 0.000 claims description 3
- 208000014060 Niemann-Pick disease Diseases 0.000 claims description 3
- 201000000794 Niemann-Pick disease type A Diseases 0.000 claims description 3
- 208000007824 Type A Niemann-Pick Disease Diseases 0.000 claims description 3
- 208000025919 mucopolysaccharidosis type 7 Diseases 0.000 claims description 3
- 208000031277 Amaurotic familial idiocy Diseases 0.000 claims description 2
- 208000035374 Chronic visceral acid sphingomyelinase deficiency Diseases 0.000 claims description 2
- 208000015178 Hurler syndrome Diseases 0.000 claims description 2
- 206010056886 Mucopolysaccharidosis I Diseases 0.000 claims description 2
- 208000025923 Mucopolysaccharidosis type 4B Diseases 0.000 claims description 2
- 208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 claims description 2
- 201000000791 Niemann-Pick disease type B Diseases 0.000 claims description 2
- 208000021811 Sandhoff disease Diseases 0.000 claims description 2
- 208000022292 Tay-Sachs disease Diseases 0.000 claims description 2
- 208000017476 juvenile neuronal ceroid lipofuscinosis Diseases 0.000 claims description 2
- 208000012091 mucopolysaccharidosis type IVB Diseases 0.000 claims description 2
- 201000007607 neuronal ceroid lipofuscinosis 3 Diseases 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims 3
- 229920001223 polyethylene glycol Polymers 0.000 claims 3
- SDOFMBGMRVAJNF-UHFFFAOYSA-N 6-aminohexane-1,2,3,4,5-pentol Chemical compound NCC(O)C(O)C(O)C(O)CO SDOFMBGMRVAJNF-UHFFFAOYSA-N 0.000 claims 2
- GODZNYBQGNSJJN-UHFFFAOYSA-N 1-aminoethane-1,2-diol Chemical compound NC(O)CO GODZNYBQGNSJJN-UHFFFAOYSA-N 0.000 claims 1
- 208000015872 Gaucher disease Diseases 0.000 claims 1
- 101710157840 Lysozyme D Proteins 0.000 claims 1
- 238000002641 enzyme replacement therapy Methods 0.000 abstract description 4
- 238000006467 substitution reaction Methods 0.000 description 113
- 210000004027 cell Anatomy 0.000 description 60
- 239000000710 homodimer Substances 0.000 description 60
- 230000001225 therapeutic effect Effects 0.000 description 34
- 230000000694 effects Effects 0.000 description 31
- 210000001519 tissue Anatomy 0.000 description 31
- 150000002632 lipids Chemical class 0.000 description 24
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 19
- 125000003275 alpha amino acid group Chemical group 0.000 description 19
- 238000004458 analytical method Methods 0.000 description 19
- 239000000523 sample Substances 0.000 description 16
- 230000003612 virological effect Effects 0.000 description 16
- 241000710127 Cricket paralysis virus Species 0.000 description 15
- 239000002502 liposome Substances 0.000 description 15
- 102000005431 Molecular Chaperones Human genes 0.000 description 14
- 108010006519 Molecular Chaperones Proteins 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 14
- 229940068935 insulin-like growth factor 2 Drugs 0.000 description 14
- 235000001014 amino acid Nutrition 0.000 description 12
- 230000014509 gene expression Effects 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 150000001413 amino acids Chemical group 0.000 description 11
- 102200018205 rs74315441 Human genes 0.000 description 11
- 239000004471 Glycine Substances 0.000 description 10
- 208000002193 Pain Diseases 0.000 description 10
- 238000012217 deletion Methods 0.000 description 10
- 230000037430 deletion Effects 0.000 description 10
- 108020001507 fusion proteins Proteins 0.000 description 10
- 102000037865 fusion proteins Human genes 0.000 description 10
- 239000001993 wax Substances 0.000 description 10
- 239000013592 cell lysate Substances 0.000 description 9
- 230000003834 intracellular effect Effects 0.000 description 9
- -1 polyethylene Polymers 0.000 description 9
- 210000002950 fibroblast Anatomy 0.000 description 8
- LXBIFEVIBLOUGU-DPYQTVNSSA-N migalastat Chemical compound OC[C@H]1NC[C@H](O)[C@@H](O)[C@H]1O LXBIFEVIBLOUGU-DPYQTVNSSA-N 0.000 description 8
- 229950007469 migalastat Drugs 0.000 description 8
- 108090000565 Capsid Proteins Proteins 0.000 description 7
- 102100037182 Cation-independent mannose-6-phosphate receptor Human genes 0.000 description 7
- 101710145225 Cation-independent mannose-6-phosphate receptor Proteins 0.000 description 7
- 102100023321 Ceruloplasmin Human genes 0.000 description 7
- 108020004414 DNA Proteins 0.000 description 7
- 102220576120 Oligodendrocyte transcription factor 1_Y27W_mutation Human genes 0.000 description 7
- 239000004698 Polyethylene Substances 0.000 description 7
- 239000013604 expression vector Substances 0.000 description 7
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 7
- 210000002706 plastid Anatomy 0.000 description 7
- 229920000573 polyethylene Polymers 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 206010011878 Deafness Diseases 0.000 description 6
- 201000011240 Frontotemporal dementia Diseases 0.000 description 6
- 208000003430 Mitral Valve Prolapse Diseases 0.000 description 6
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 6
- 208000001647 Renal Insufficiency Diseases 0.000 description 6
- 208000009205 Tinnitus Diseases 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 239000000539 dimer Substances 0.000 description 6
- 230000007160 gastrointestinal dysfunction Effects 0.000 description 6
- 230000010370 hearing loss Effects 0.000 description 6
- 231100000888 hearing loss Toxicity 0.000 description 6
- 208000016354 hearing loss disease Diseases 0.000 description 6
- 208000019622 heart disease Diseases 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 201000006370 kidney failure Diseases 0.000 description 6
- 102000040430 polynucleotide Human genes 0.000 description 6
- 108091033319 polynucleotide Proteins 0.000 description 6
- 239000002157 polynucleotide Substances 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 230000008085 renal dysfunction Effects 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 210000004243 sweat Anatomy 0.000 description 6
- 231100000886 tinnitus Toxicity 0.000 description 6
- 238000012546 transfer Methods 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 5
- 102220486129 Alpha-galactosidase A_R49S_mutation Human genes 0.000 description 5
- 102220511796 F-actin-capping protein subunit beta_F26S_mutation Human genes 0.000 description 5
- 102220487360 Guanine nucleotide-binding protein G(i) subunit alpha-1_A54R_mutation Human genes 0.000 description 5
- 102220474905 Insulin-like 3_V43L_mutation Human genes 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 239000000693 micelle Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 102220332512 rs1555032911 Human genes 0.000 description 5
- 102220057316 rs730880446 Human genes 0.000 description 5
- 102220297864 rs761846391 Human genes 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- YUDPTGPSBJVHCN-CHUNWDLHSA-N 4-methylumbelliferyl alpha-D-galactoside Chemical compound C1=CC=2C(C)=CC(=O)OC=2C=C1O[C@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O YUDPTGPSBJVHCN-CHUNWDLHSA-N 0.000 description 4
- 108010062580 Concanavalin A Proteins 0.000 description 4
- 108060003951 Immunoglobulin Proteins 0.000 description 4
- 102220638483 Protein PML_K65R_mutation Human genes 0.000 description 4
- 206010040829 Skin discolouration Diseases 0.000 description 4
- 230000008030 elimination Effects 0.000 description 4
- 238000003379 elimination reaction Methods 0.000 description 4
- 230000005284 excitation Effects 0.000 description 4
- 102000018358 immunoglobulin Human genes 0.000 description 4
- 238000011813 knockout mouse model Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 238000011002 quantification Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 102220012182 rs373164247 Human genes 0.000 description 4
- 230000037370 skin discoloration Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 210000001082 somatic cell Anatomy 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 230000014621 translational initiation Effects 0.000 description 4
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 3
- 239000013607 AAV vector Substances 0.000 description 3
- 102000016736 Cyclin Human genes 0.000 description 3
- 108050006400 Cyclin Proteins 0.000 description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 101100118093 Drosophila melanogaster eEF1alpha2 gene Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 239000000232 Lipid Bilayer Substances 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- 102220536041 Quinone oxidoreductase-like protein 1_P31G_mutation Human genes 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- JLQUFIHWVLZVTJ-UHFFFAOYSA-N carbosulfan Chemical compound CCCCN(CCCC)SN(C)C(=O)OC1=CC=CC2=C1OC(C)(C)C2 JLQUFIHWVLZVTJ-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000003636 conditioned culture medium Substances 0.000 description 3
- 238000009585 enzyme analysis Methods 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 239000006166 lysate Substances 0.000 description 3
- 210000004962 mammalian cell Anatomy 0.000 description 3
- 229940074869 marquis Drugs 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 150000003904 phospholipids Chemical class 0.000 description 3
- VBUNOIXRZNJNAD-UHFFFAOYSA-N ponazuril Chemical compound CC1=CC(N2C(N(C)C(=O)NC2=O)=O)=CC=C1OC1=CC=C(S(=O)(=O)C(F)(F)F)C=C1 VBUNOIXRZNJNAD-UHFFFAOYSA-N 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 230000001568 sexual effect Effects 0.000 description 3
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000010474 transient expression Effects 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- GRGNVOCPFLXGDQ-TWHXEDJUSA-N (2r,3r,4s,5r,6r)-2-[(2r,3r,4r,5r,6s)-6-[(2r,3s,4r,5r,6r)-6-[(e,2s,3r)-2-amino-3-hydroxyoctadec-4-enoxy]-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-4,5-dihydroxy-2-(hydroxymethyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](N)[C@H](O)/C=C/CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)[C@@H](CO)O1 GRGNVOCPFLXGDQ-TWHXEDJUSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 2
- 241000202702 Adeno-associated virus - 3 Species 0.000 description 2
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 2
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 2
- 241001164823 Adeno-associated virus - 7 Species 0.000 description 2
- 241001164825 Adeno-associated virus - 8 Species 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 2
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 108700041152 Endoplasmic Reticulum Chaperone BiP Proteins 0.000 description 2
- 102100021451 Endoplasmic reticulum chaperone BiP Human genes 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 2
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 description 2
- 208000010557 Lipid storage disease Diseases 0.000 description 2
- 206010027374 Mental impairment Diseases 0.000 description 2
- 208000007101 Muscle Cramp Diseases 0.000 description 2
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 241000714474 Rous sarcoma virus Species 0.000 description 2
- 108700019146 Transgenes Proteins 0.000 description 2
- 108700005077 Viral Genes Proteins 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 201000007201 aphasia Diseases 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 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 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 229940106189 ceramide Drugs 0.000 description 2
- 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 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- RNPXCFINMKSQPQ-UHFFFAOYSA-N dicetyl hydrogen phosphate Chemical compound CCCCCCCCCCCCCCCCOP(O)(=O)OCCCCCCCCCCCCCCCC RNPXCFINMKSQPQ-UHFFFAOYSA-N 0.000 description 2
- 238000006471 dimerization reaction Methods 0.000 description 2
- 238000002845 discoloration Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 238000011304 droplet digital PCR Methods 0.000 description 2
- 229940088679 drug related substance Drugs 0.000 description 2
- 238000001962 electrophoresis Methods 0.000 description 2
- 230000012202 endocytosis Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 230000009395 genetic defect Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 210000004602 germ cell Anatomy 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 102000028416 insulin-like growth factor binding Human genes 0.000 description 2
- 108091022911 insulin-like growth factor binding Proteins 0.000 description 2
- 238000000185 intracerebroventricular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 208000014416 lysosomal lipid storage disease Diseases 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 2
- 239000002773 nucleotide Substances 0.000 description 2
- 125000003729 nucleotide group Chemical group 0.000 description 2
- 230000001177 retroviral effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 210000000278 spinal cord Anatomy 0.000 description 2
- 238000013112 stability test Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000010361 transduction Methods 0.000 description 2
- 230000026683 transduction Effects 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000714230 Avian leukemia virus Species 0.000 description 1
- 102000006734 Beta-Globulins Human genes 0.000 description 1
- 108010087504 Beta-Globulins Proteins 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 238000011740 C57BL/6 mouse Methods 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 101710163595 Chaperone protein DnaK Proteins 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 102000004420 Creatine Kinase Human genes 0.000 description 1
- 108010042126 Creatine kinase Proteins 0.000 description 1
- 241001289493 Cripavirus Species 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical compound COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 description 1
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 102000004366 Glucosidases Human genes 0.000 description 1
- 108010056771 Glucosidases Proteins 0.000 description 1
- 101150112743 HSPA5 gene Proteins 0.000 description 1
- 101710178376 Heat shock 70 kDa protein Proteins 0.000 description 1
- 101710152018 Heat shock cognate 70 kDa protein Proteins 0.000 description 1
- 208000005176 Hepatitis C Diseases 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 102100037852 Insulin-like growth factor I Human genes 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 108050001602 Lysosomal thioesterase PPT2 Proteins 0.000 description 1
- 102100034502 Lysosomal thioesterase PPT2 Human genes 0.000 description 1
- 102000003792 Metallothionein Human genes 0.000 description 1
- 108090000157 Metallothionein Proteins 0.000 description 1
- 241000713333 Mouse mammary tumor virus Species 0.000 description 1
- 102000003505 Myosin Human genes 0.000 description 1
- 108060008487 Myosin Proteins 0.000 description 1
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 description 1
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 1
- WHCJUIFHMJFEFZ-UIAUGNHASA-N N-acetyl-beta-D-galactosamine 4-sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS(O)(=O)=O)[C@@H]1O WHCJUIFHMJFEFZ-UIAUGNHASA-N 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010077524 Peptide Elongation Factor 1 Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- 206010035148 Plague Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 102000018120 Recombinases Human genes 0.000 description 1
- 108010091086 Recombinases Proteins 0.000 description 1
- 241000936948 Rhopalosiphum padi virus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 239000011542 SDS running buffer Substances 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 102100037116 Transcription elongation factor 1 homolog Human genes 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 108010049936 agalsidase alfa Proteins 0.000 description 1
- 108010056760 agalsidase beta Proteins 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical group [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000000823 artificial membrane Substances 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000003012 bilayer membrane Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 210000000234 capsid Anatomy 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 125000001549 ceramide group Chemical group 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 230000035071 co-translational protein modification Effects 0.000 description 1
- 238000001246 colloidal dispersion Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 229940093541 dicetylphosphate Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- BPHQZTVXXXJVHI-UHFFFAOYSA-N dimyristoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCC BPHQZTVXXXJVHI-UHFFFAOYSA-N 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- CYFHLEMYBPQRGN-UHFFFAOYSA-N ditetradecyl hydrogen phosphate Chemical compound CCCCCCCCCCCCCCOP(O)(=O)OCCCCCCCCCCCCCC CYFHLEMYBPQRGN-UHFFFAOYSA-N 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000009088 enzymatic function Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 229940014516 fabrazyme Drugs 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 150000003278 haem Chemical class 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 208000005252 hepatitis A Diseases 0.000 description 1
- 244000144980 herd Species 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000012744 immunostaining Methods 0.000 description 1
- 238000012750 in vivo screening Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 102000033648 insulin receptor binding proteins Human genes 0.000 description 1
- 108091009639 insulin receptor binding proteins Proteins 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- NBQNWMBBSKPBAY-UHFFFAOYSA-N iodixanol Chemical compound IC=1C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C(I)C=1N(C(=O)C)CC(O)CN(C(C)=O)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NBQNWMBBSKPBAY-UHFFFAOYSA-N 0.000 description 1
- 229960004359 iodixanol Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 125000003473 lipid group Chemical group 0.000 description 1
- 238000001638 lipofection Methods 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 229960003151 mercaptamine Drugs 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 238000000520 microinjection Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000013580 millipore water Substances 0.000 description 1
- 102000035118 modified proteins Human genes 0.000 description 1
- 108091005573 modified proteins Proteins 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- 239000002088 nanocapsule Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 208000037920 primary disease Diseases 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 230000020978 protein processing Effects 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000012723 sample buffer Substances 0.000 description 1
- 210000001044 sensory neuron Anatomy 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- CIJQGPVMMRXSQW-UHFFFAOYSA-M sodium;2-aminoacetic acid;hydroxide Chemical compound O.[Na+].NCC([O-])=O CIJQGPVMMRXSQW-UHFFFAOYSA-M 0.000 description 1
- ALZJERAWTOKHNO-UHFFFAOYSA-M sodium;dodecyl sulfate;3-morpholin-4-ylpropane-1-sulfonic acid Chemical compound [Na+].OS(=O)(=O)CCCN1CCOCC1.CCCCCCCCCCCCOS([O-])(=O)=O ALZJERAWTOKHNO-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000012430 stability testing Methods 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 210000002330 subarachnoid space Anatomy 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000013520 translational research Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 150000004043 trisaccharides Chemical class 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
- A61K48/0058—Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/0008—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
- A61K48/0025—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid
- A61K48/0033—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid the non-active part being non-polymeric
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
- C12N9/2465—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1) acting on alpha-galactose-glycoside bonds, e.g. alpha-galactosidase (3.2.1.22)
-
- 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)
- C12Y302/01017—Lysozyme (3.2.1.17)
-
- 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)
- C12Y302/01022—Alpha-galactosidase (3.2.1.22)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/35—Fusion polypeptide containing a fusion for enhanced stability/folding during expression, e.g. fusions with chaperones or thioredoxin
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
- C12N2750/00011—Details
- C12N2750/14011—Parvoviridae
- C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
- C12N2750/14141—Use of virus, viral particle or viral elements as a vector
- C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2800/00—Nucleic acids vectors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/02—Thioester hydrolases (3.1.2)
- C12Y301/02022—Palmitoyl-protein hydrolase (3.1.2.22)
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Microbiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Virology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862744069P | 2018-10-10 | 2018-10-10 | |
| US62/744,069 | 2018-10-10 | ||
| WOPCT/US19/55679 | 2019-10-10 | ||
| PCT/US2019/055679 WO2020077114A2 (en) | 2018-10-10 | 2019-10-10 | Disulfide bond stabilized polypeptide compositions and methods of use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202027781A true TW202027781A (zh) | 2020-08-01 |
Family
ID=68425288
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW108136956A TW202027781A (zh) | 2018-10-10 | 2019-10-14 | 雙硫鍵穩定化之多肽組合物及使用方法 |
Country Status (17)
| Country | Link |
|---|---|
| US (3) | US11097015B2 (https=) |
| EP (1) | EP3863663A2 (https=) |
| JP (1) | JP7577650B2 (https=) |
| KR (1) | KR102743734B1 (https=) |
| CN (1) | CN113631182B (https=) |
| AR (1) | AR116624A1 (https=) |
| AU (1) | AU2019359385B2 (https=) |
| BR (1) | BR112021006829A2 (https=) |
| CA (1) | CA3115944A1 (https=) |
| CL (1) | CL2021000883A1 (https=) |
| EA (1) | EA202190999A1 (https=) |
| IL (1) | IL282205A (https=) |
| MX (1) | MX2021004188A (https=) |
| PH (1) | PH12021550789A1 (https=) |
| SG (1) | SG11202103640VA (https=) |
| TW (1) | TW202027781A (https=) |
| WO (1) | WO2020077114A2 (https=) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102712926B1 (ko) | 2016-10-20 | 2024-10-07 | 상가모 테라퓨틱스, 인코포레이티드 | 파브리병의 치료를 위한 방법 및 조성물 |
| CN113631182B (zh) | 2018-10-10 | 2025-03-21 | 阿米库斯治疗学公司 | 二硫键稳定的多肽组合物和使用方法 |
| KR20210148101A (ko) | 2019-02-04 | 2021-12-07 | 프리라인 테라퓨틱스 리미티드 | 폴리뉴클레오티드 |
| AU2021356684A1 (en) * | 2020-10-09 | 2023-05-11 | The Trustees Of The University Of Pennsylvania | Compositions and methods for treatment of fabry disease |
| AR124981A1 (es) * | 2021-02-26 | 2023-05-24 | Takeda Pharmaceuticals Co | Composición y métodos para el tratamiento de la enfermedad de fabry |
| KR20240133693A (ko) * | 2021-11-12 | 2024-09-04 | 더 트러스티스 오브 더 유니버시티 오브 펜실베니아 | 점액다당류증 iiia의 치료를 위한 유전자 요법 |
| WO2023086939A1 (en) * | 2021-11-12 | 2023-05-19 | Amicus Therapeutics, Inc. | Compositions and methods for treating mucopolysaccharidosis iiia |
| US20240408157A1 (en) * | 2021-12-02 | 2024-12-12 | The Trustees Of The University Of Pennsylvania | Compositions and methods for treatment of fabry disease |
| KR20250161626A (ko) * | 2023-03-20 | 2025-11-17 | 스파크 테라퓨틱스, 인코포레이티드 | Ppt1 유전자 치료 |
| WO2025092951A1 (en) * | 2023-11-03 | 2025-05-08 | Shanghai Vitalgen Biopharma Co., Ltd. | Recombinant adeno-associated viral vectors for treating fabry disease |
| WO2025264978A2 (en) | 2024-06-20 | 2025-12-26 | Amicus Therapeutics, Inc. | Recombinant alpha-galactosidase a proteins and gene therapy |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1133517T3 (da) | 1998-11-24 | 2009-11-23 | Bristol Myers Squibb Co | Intranuklear målrettet transport af forbindelser ved hjælp af 70 kd varmeshock-protein |
| HK1047109A1 (zh) | 1999-10-15 | 2003-02-07 | University Of Massachusetts | 作为指定基因干预工具的rna干预轨迹基因 |
| US6326193B1 (en) | 1999-11-05 | 2001-12-04 | Cambria Biosciences, Llc | Insect control agent |
| EP1118334A1 (en) | 2000-01-11 | 2001-07-25 | Aventis Behring Gesellschaft mit beschränkter Haftung | Method for the production of conjugates and uses thereof for the prevention and treatment of allergic reactions and autoimmune diseases |
| AU2001275474A1 (en) | 2000-06-12 | 2001-12-24 | Akkadix Corporation | Materials and methods for the control of nematodes |
| WO2002087510A2 (en) | 2001-04-30 | 2002-11-07 | Symbiontics, Inc. | Subcellular targeting of therapeutic proteins |
| US7629309B2 (en) | 2002-05-29 | 2009-12-08 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
| US7560424B2 (en) | 2001-04-30 | 2009-07-14 | Zystor Therapeutics, Inc. | Targeted therapeutic proteins |
| US20030072761A1 (en) | 2001-10-16 | 2003-04-17 | Lebowitz Jonathan | Methods and compositions for targeting proteins across the blood brain barrier |
| AU2002347910A1 (en) | 2001-10-16 | 2003-04-28 | Symbiontics Inc. | Methods and compositions for targeting proteins across the blood brain barrier |
| ES2371913T3 (es) | 2003-01-22 | 2012-01-11 | Duke University | Constructos mejorados para expresar polipéptidos lisosomales. |
| EP1620133B1 (en) | 2003-05-01 | 2015-12-09 | Genzyme Corporation | Gene therapy for neurometabolic disorders |
| US7355018B2 (en) | 2003-09-30 | 2008-04-08 | Regeneron Pharmaceuticals, Inc. | Modified IGF1 polypeptides with increased stability and potency |
| EP1689766B1 (en) | 2003-11-06 | 2012-04-25 | Danisco US Inc. | Expression in filamentous fungi of protease inhibitors and variants thereof |
| CA2553955C (en) | 2004-02-10 | 2012-08-28 | Zystor Therapeutics, Inc. | Acid alpha-glucosidase and fragments thereof |
| US8889127B2 (en) | 2004-07-01 | 2014-11-18 | Icahn School Of Medicine At Mount Sinai | Targeted protein replacement for the treatment of lysosomal storage disorders |
| DE602007007923D1 (de) | 2006-04-11 | 2010-09-02 | Csl Behring Gmbh | Verfahren zur erhöhung der in-vivo-gewinnung therapeutischer polypeptide |
| EP2099523A2 (en) | 2006-11-13 | 2009-09-16 | ZyStor Therapeutics , Inc. | Methods for treating pompe disease |
| JP5627571B2 (ja) | 2008-05-07 | 2014-11-19 | バイオマリン ファーマシューティカル インコーポレイテッド | リソソーム標的化ペプチドおよびその使用 |
| ES3000111T3 (en) | 2009-02-13 | 2025-02-27 | Immunomedics Inc | Intermediates for preparing conjugates with an intracellularly-cleavable linkage |
| ES2829199T3 (es) | 2010-11-22 | 2021-05-31 | Amicus Therapeutics Inc | Nuevas secuencias de señalización para mejorar la expresión y segregación de proteínas de enzimas recombinantes y otras proteínas |
| US8580922B2 (en) | 2011-03-04 | 2013-11-12 | Shire Human Genetic Therapies, Inc. | Peptide linkers for polypeptide compositions and methods for using same |
| CN103443273B (zh) | 2011-03-16 | 2016-10-26 | 天野酶制品株式会社 | 修饰型α-葡萄糖苷酶及其用途 |
| HRP20180291T1 (hr) | 2011-05-27 | 2018-03-23 | Amicus Therapeutics, Inc. | Postupci za sparivanje ciljajućeg peptida na rekombinantne lizosomalne enzime za poboljšano liječenje lizosomskih bolesti nakupljanja |
| CA3140358A1 (en) * | 2012-07-31 | 2014-02-06 | Bioasis Technologies, Inc. | Dephosphorylated lysosomal storage disease proteins and methods of use thereof |
| ES2729997T3 (es) | 2012-11-27 | 2019-11-07 | Biomarin Pharm Inc | Proteínas de fusión terapéuticas dirigidas de enzima lisosómica y usos de las mismas |
| AU2014228231B2 (en) | 2013-03-15 | 2019-02-21 | Amicus Therapeutics, Inc. | Chemical crosslinkers |
| CN105745326A (zh) | 2013-10-24 | 2016-07-06 | 优尼科Ip有限公司 | 用于基因治疗神经疾病的aav-5假型载体 |
| WO2015085238A1 (en) | 2013-12-05 | 2015-06-11 | The Regents Of The University Of California, A California Corporation | Inhibitors of lpxc |
| GB201508025D0 (en) | 2015-05-11 | 2015-06-24 | Ucl Business Plc | Fabry disease gene therapy |
| US20170051267A1 (en) * | 2015-08-20 | 2017-02-23 | Research Foundation Of The City University Of New York | Novel alpha-galactosidase a derivatives |
| BR112020021962A2 (pt) | 2018-04-30 | 2021-01-26 | Amicus Therapeutics, Inc. | construtos para terapia gênica e métodos de uso |
| CN113631182B (zh) | 2018-10-10 | 2025-03-21 | 阿米库斯治疗学公司 | 二硫键稳定的多肽组合物和使用方法 |
-
2019
- 2019-10-10 CN CN201980078576.0A patent/CN113631182B/zh active Active
- 2019-10-10 WO PCT/US2019/055679 patent/WO2020077114A2/en not_active Ceased
- 2019-10-10 CA CA3115944A patent/CA3115944A1/en active Pending
- 2019-10-10 EP EP19797444.7A patent/EP3863663A2/en active Pending
- 2019-10-10 BR BR112021006829-5A patent/BR112021006829A2/pt not_active IP Right Cessation
- 2019-10-10 KR KR1020217013640A patent/KR102743734B1/ko active Active
- 2019-10-10 EA EA202190999A patent/EA202190999A1/ru unknown
- 2019-10-10 AR ARP190102882A patent/AR116624A1/es not_active Application Discontinuation
- 2019-10-10 AU AU2019359385A patent/AU2019359385B2/en active Active
- 2019-10-10 MX MX2021004188A patent/MX2021004188A/es unknown
- 2019-10-10 SG SG11202103640VA patent/SG11202103640VA/en unknown
- 2019-10-10 JP JP2021520223A patent/JP7577650B2/ja active Active
- 2019-10-10 US US16/598,960 patent/US11097015B2/en active Active
- 2019-10-14 TW TW108136956A patent/TW202027781A/zh unknown
-
2021
- 2021-04-09 CL CL2021000883A patent/CL2021000883A1/es unknown
- 2021-04-09 IL IL282205A patent/IL282205A/en unknown
- 2021-04-09 PH PH12021550789A patent/PH12021550789A1/en unknown
- 2021-06-30 US US17/363,333 patent/US12064485B2/en active Active
-
2024
- 2024-08-19 US US18/808,596 patent/US20250242057A1/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP7577650B2 (ja) | 2024-11-05 |
| EP3863663A2 (en) | 2021-08-18 |
| JP2022512689A (ja) | 2022-02-07 |
| IL282205A (en) | 2021-05-31 |
| PH12021550789A1 (en) | 2021-10-25 |
| WO2020077114A3 (en) | 2020-07-23 |
| KR20210075125A (ko) | 2021-06-22 |
| EA202190999A1 (ru) | 2021-10-15 |
| US20250242057A1 (en) | 2025-07-31 |
| AU2019359385A1 (en) | 2021-05-13 |
| AU2019359385B2 (en) | 2024-07-25 |
| MX2021004188A (es) | 2021-09-08 |
| AR116624A1 (es) | 2021-05-26 |
| BR112021006829A2 (pt) | 2021-07-20 |
| CN113631182B (zh) | 2025-03-21 |
| US11097015B2 (en) | 2021-08-24 |
| KR102743734B1 (ko) | 2024-12-17 |
| SG11202103640VA (en) | 2021-05-28 |
| US12064485B2 (en) | 2024-08-20 |
| CA3115944A1 (en) | 2020-04-16 |
| CN113631182A (zh) | 2021-11-09 |
| US20200147241A1 (en) | 2020-05-14 |
| WO2020077114A2 (en) | 2020-04-16 |
| US20220023443A1 (en) | 2022-01-27 |
| CL2021000883A1 (es) | 2021-11-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US12064485B2 (en) | Disulfide bond stabilized polypeptide compositions and methods of use | |
| US12310997B2 (en) | Compositions and methods of treating ocular diseases | |
| CN111902539B (zh) | 杂合调控元件 | |
| JP2019163281A (ja) | 脳疾患を処置するための方法および組成物 | |
| TW202003053A (zh) | 基因治療構築體及使用方法 | |
| JP2021503914A (ja) | アデノ随伴ウイルス変異キャプシドおよび血管新生の阻害のための使用 | |
| TW202128740A (zh) | 變體ｉｇｆ２構築體 | |
| JP2019533992A (ja) | 酸性αグルコシダーゼ変異体及びその使用 | |
| US20250213730A1 (en) | Gene therapy for diseases with cns manifestations | |
| CN114555808A (zh) | 嵌合多肽及其用途 | |
| HK40053744A (zh) | 二硫键稳定的多肽组合物和使用方法 | |
| HK40053744B (zh) | 二硫键稳定的多肽组合物和使用方法 | |
| US20250269068A1 (en) | Gene Therapy for NMNAT1-Associated Retinal Degeneration | |
| HK40039189A (en) | Gene therapy constructs and methods of use |