IL293068A - Therapeutic adeno-associated virus comprising liver-specific promoters for treating pompe disease and lysosomal disorders - Google Patents
Therapeutic adeno-associated virus comprising liver-specific promoters for treating pompe disease and lysosomal disordersInfo
- Publication number
- IL293068A IL293068A IL293068A IL29306822A IL293068A IL 293068 A IL293068 A IL 293068A IL 293068 A IL293068 A IL 293068A IL 29306822 A IL29306822 A IL 29306822A IL 293068 A IL293068 A IL 293068A
- Authority
- IL
- Israel
- Prior art keywords
- seq
- nucleic acid
- sequence
- gaa
- aav vector
- Prior art date
Links
- 210000004185 liver Anatomy 0.000 title claims description 216
- 206010053185 Glycogen storage disease type II Diseases 0.000 title claims description 32
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 title claims description 28
- 201000004502 glycogen storage disease II Diseases 0.000 title claims description 27
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 title claims description 23
- 208000015439 Lysosomal storage disease Diseases 0.000 title claims description 18
- 241000702421 Dependoparvovirus Species 0.000 title description 98
- 238000011282 treatment Methods 0.000 title description 15
- 230000001225 therapeutic effect Effects 0.000 title description 7
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 554
- 150000007523 nucleic acids Chemical group 0.000 claims description 386
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 344
- 229920001184 polypeptide Polymers 0.000 claims description 339
- 108010076504 Protein Sorting Signals Proteins 0.000 claims description 243
- 230000008685 targeting Effects 0.000 claims description 217
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 195
- 102000039446 nucleic acids Human genes 0.000 claims description 183
- 108020004707 nucleic acids Proteins 0.000 claims description 183
- 150000001413 amino acids Chemical class 0.000 claims description 143
- 230000003248 secreting effect Effects 0.000 claims description 140
- 230000000694 effects Effects 0.000 claims description 124
- 239000013607 AAV vector Substances 0.000 claims description 121
- 239000002773 nucleotide Substances 0.000 claims description 111
- 125000003729 nucleotide group Chemical group 0.000 claims description 111
- 238000000034 method Methods 0.000 claims description 106
- 238000012986 modification Methods 0.000 claims description 92
- 230000004048 modification Effects 0.000 claims description 91
- 230000014509 gene expression Effects 0.000 claims description 85
- 239000012634 fragment Substances 0.000 claims description 82
- 239000013598 vector Substances 0.000 claims description 58
- 102100037362 Fibronectin Human genes 0.000 claims description 57
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 55
- 108010067306 Fibronectins Proteins 0.000 claims description 53
- 108010002350 Interleukin-2 Proteins 0.000 claims description 50
- 125000006850 spacer group Chemical group 0.000 claims description 48
- 230000004927 fusion Effects 0.000 claims description 44
- 210000001519 tissue Anatomy 0.000 claims description 42
- 102000005962 receptors Human genes 0.000 claims description 39
- 108020003175 receptors Proteins 0.000 claims description 39
- 238000006467 substitution reaction Methods 0.000 claims description 33
- 108010028144 alpha-Glucosidases Proteins 0.000 claims description 32
- 101001076292 Homo sapiens Insulin-like growth factor II Proteins 0.000 claims description 31
- 238000012217 deletion Methods 0.000 claims description 30
- 230000037430 deletion Effects 0.000 claims description 30
- 108020004705 Codon Proteins 0.000 claims description 29
- 210000003205 muscle Anatomy 0.000 claims description 26
- 101710145225 Cation-independent mannose-6-phosphate receptor Proteins 0.000 claims description 24
- 102100037182 Cation-independent mannose-6-phosphate receptor Human genes 0.000 claims description 24
- 108090000565 Capsid Proteins Proteins 0.000 claims description 23
- 102100023321 Ceruloplasmin Human genes 0.000 claims description 23
- 241000282414 Homo sapiens Species 0.000 claims description 23
- 108020001507 fusion proteins Proteins 0.000 claims description 23
- 102000037865 fusion proteins Human genes 0.000 claims description 23
- 241001164825 Adeno-associated virus - 8 Species 0.000 claims description 22
- 230000002132 lysosomal effect Effects 0.000 claims description 22
- 210000004899 c-terminal region Anatomy 0.000 claims description 20
- 108091029523 CpG island Proteins 0.000 claims description 19
- 102100025947 Insulin-like growth factor II Human genes 0.000 claims description 18
- 230000035772 mutation Effects 0.000 claims description 18
- 102000028416 insulin-like growth factor binding Human genes 0.000 claims description 16
- 108091022911 insulin-like growth factor binding Proteins 0.000 claims description 16
- 238000003780 insertion Methods 0.000 claims description 15
- 230000037431 insertion Effects 0.000 claims description 15
- 108010035532 Collagen Proteins 0.000 claims description 14
- 102000008186 Collagen Human genes 0.000 claims description 14
- 229920001436 collagen Polymers 0.000 claims description 14
- 230000015788 innate immune response Effects 0.000 claims description 14
- 101150115151 GAA gene Proteins 0.000 claims description 12
- 238000001727 in vivo Methods 0.000 claims description 12
- 102000038460 IGF Type 2 Receptor Human genes 0.000 claims description 11
- 108010031792 IGF Type 2 Receptor Proteins 0.000 claims description 10
- 108020005345 3' Untranslated Regions Proteins 0.000 claims description 9
- 229920002527 Glycogen Polymers 0.000 claims description 8
- 229940096919 glycogen Drugs 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- YNVAHBUBGBLIEY-WGDLNXRISA-N (1e,4e)-1,5-bis(2-hydroxyphenyl)penta-1,4-dien-3-one Chemical group OC1=CC=CC=C1\C=C\C(=O)\C=C\C1=CC=CC=C1O YNVAHBUBGBLIEY-WGDLNXRISA-N 0.000 claims description 6
- 101001028831 Homo sapiens Cation-independent mannose-6-phosphate receptor Proteins 0.000 claims description 6
- 230000007423 decrease Effects 0.000 claims description 6
- 210000004165 myocardium Anatomy 0.000 claims description 6
- 210000002027 skeletal muscle Anatomy 0.000 claims description 6
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 5
- 101100236307 Homo sapiens GAA gene Proteins 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 230000009467 reduction Effects 0.000 claims description 5
- 241000701161 unidentified adenovirus Species 0.000 claims description 5
- 208000020584 Polyploidy Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 108091036066 Three prime untranslated region Proteins 0.000 claims description 3
- 230000007812 deficiency Effects 0.000 claims description 3
- 210000002966 serum Anatomy 0.000 claims description 3
- 241000202702 Adeno-associated virus - 3 Species 0.000 claims description 2
- 239000002299 complementary DNA Substances 0.000 claims description 2
- 238000007918 intramuscular administration Methods 0.000 claims description 2
- 238000007913 intrathecal administration Methods 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 238000007920 subcutaneous administration Methods 0.000 claims description 2
- 102100021244 Integral membrane protein GPR180 Human genes 0.000 claims 2
- 102220015681 rs145500807 Human genes 0.000 claims 2
- 241001502050 Acis Species 0.000 claims 1
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 description 224
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 description 219
- 235000001014 amino acid Nutrition 0.000 description 153
- 229940024606 amino acid Drugs 0.000 description 140
- 108090000623 proteins and genes Proteins 0.000 description 115
- 102000040945 Transcription factor Human genes 0.000 description 99
- 108091023040 Transcription factor Proteins 0.000 description 99
- 239000000203 mixture Substances 0.000 description 94
- 101001018026 Homo sapiens Lysosomal alpha-glucosidase Proteins 0.000 description 85
- 102000045921 human GAA Human genes 0.000 description 85
- 210000004027 cell Anatomy 0.000 description 81
- 102000004169 proteins and genes Human genes 0.000 description 77
- 108091062157 Cis-regulatory element Proteins 0.000 description 74
- 235000018102 proteins Nutrition 0.000 description 74
- 239000013608 rAAV vector Substances 0.000 description 69
- 102100020873 Interleukin-2 Human genes 0.000 description 42
- 210000003712 lysosome Anatomy 0.000 description 37
- 230000001868 lysosomic effect Effects 0.000 description 37
- 210000002845 virion Anatomy 0.000 description 37
- 241000700605 Viruses Species 0.000 description 36
- 210000000234 capsid Anatomy 0.000 description 28
- 108090000790 Enzymes Proteins 0.000 description 26
- 108700009124 Transcription Initiation Site Proteins 0.000 description 26
- 238000005516 engineering process Methods 0.000 description 26
- 102000004190 Enzymes Human genes 0.000 description 25
- 229940088598 enzyme Drugs 0.000 description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 23
- 102000016679 alpha-Glucosidases Human genes 0.000 description 22
- 241000125945 Protoparvovirus Species 0.000 description 20
- 125000000539 amino acid group Chemical group 0.000 description 19
- 238000010361 transduction Methods 0.000 description 19
- 230000026683 transduction Effects 0.000 description 19
- 230000010415 tropism Effects 0.000 description 18
- NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 description 17
- 210000005229 liver cell Anatomy 0.000 description 17
- 238000011144 upstream manufacturing Methods 0.000 description 17
- 230000028327 secretion Effects 0.000 description 16
- 230000003612 virological effect Effects 0.000 description 16
- 230000000295 complement effect Effects 0.000 description 15
- 201000010099 disease Diseases 0.000 description 15
- 239000002245 particle Substances 0.000 description 15
- 238000012545 processing Methods 0.000 description 15
- 238000013518 transcription Methods 0.000 description 15
- 230000035897 transcription Effects 0.000 description 15
- 238000003776 cleavage reaction Methods 0.000 description 14
- 102000057877 human IGF2 Human genes 0.000 description 14
- 230000002209 hydrophobic effect Effects 0.000 description 14
- -1 mannose carbohydrate Chemical class 0.000 description 14
- 230000007017 scission Effects 0.000 description 14
- 230000008901 benefit Effects 0.000 description 13
- 230000006870 function Effects 0.000 description 13
- 108010045758 lysosomal proteins Proteins 0.000 description 13
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 12
- 230000001105 regulatory effect Effects 0.000 description 12
- 102100022057 Hepatocyte nuclear factor 1-alpha Human genes 0.000 description 11
- 101001045751 Homo sapiens Hepatocyte nuclear factor 1-alpha Proteins 0.000 description 11
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 11
- 210000003169 central nervous system Anatomy 0.000 description 11
- 102000004961 Furin Human genes 0.000 description 10
- 108090001126 Furin Proteins 0.000 description 10
- 102000035195 Peptidases Human genes 0.000 description 10
- 108091005804 Peptidases Proteins 0.000 description 10
- 210000004962 mammalian cell Anatomy 0.000 description 10
- 210000000663 muscle cell Anatomy 0.000 description 10
- 208000024891 symptom Diseases 0.000 description 10
- 102220576120 Oligodendrocyte transcription factor 1_Y27W_mutation Human genes 0.000 description 9
- 239000003623 enhancer Substances 0.000 description 9
- 102000040430 polynucleotide Human genes 0.000 description 9
- 108091033319 polynucleotide Proteins 0.000 description 9
- 239000002157 polynucleotide Substances 0.000 description 9
- 230000002441 reversible effect Effects 0.000 description 9
- 241000702423 Adeno-associated virus - 2 Species 0.000 description 8
- 108010031794 IGF Type 1 Receptor Proteins 0.000 description 8
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 239000002243 precursor Substances 0.000 description 8
- 238000012384 transportation and delivery Methods 0.000 description 8
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 7
- 108091026890 Coding region Proteins 0.000 description 7
- 108091035707 Consensus sequence Proteins 0.000 description 7
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 7
- 102100039688 Insulin-like growth factor 1 receptor Human genes 0.000 description 7
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 7
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 239000004365 Protease Substances 0.000 description 7
- 101150110932 US19 gene Proteins 0.000 description 7
- 108010067390 Viral Proteins Proteins 0.000 description 7
- 238000007792 addition Methods 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 230000014759 maintenance of location Effects 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 7
- 230000001737 promoting effect Effects 0.000 description 7
- 235000019419 proteases Nutrition 0.000 description 7
- 101710186200 CCAAT/enhancer-binding protein Proteins 0.000 description 6
- 102100022054 Hepatocyte nuclear factor 4-alpha Human genes 0.000 description 6
- 101001045740 Homo sapiens Hepatocyte nuclear factor 4-alpha Proteins 0.000 description 6
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 description 6
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 6
- 108060001084 Luciferase Proteins 0.000 description 6
- 239000005089 Luciferase Substances 0.000 description 6
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 210000004556 brain Anatomy 0.000 description 6
- 150000001768 cations Chemical class 0.000 description 6
- 238000001415 gene therapy Methods 0.000 description 6
- 230000002265 prevention Effects 0.000 description 6
- 229930002330 retinoic acid Natural products 0.000 description 6
- SHGAZHPCJJPHSC-YCNIQYBTSA-N retinoic acid group Chemical group C\C(=C/C(=O)O)\C=C\C=C(\C=C\C1=C(CCCC1(C)C)C)/C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 6
- 229960001727 tretinoin Drugs 0.000 description 6
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 6
- 235000002374 tyrosine Nutrition 0.000 description 6
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 5
- 108700019146 Transgenes Proteins 0.000 description 5
- 235000014633 carbohydrates Nutrition 0.000 description 5
- 230000000747 cardiac effect Effects 0.000 description 5
- 210000004413 cardiac myocyte Anatomy 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 5
- 230000013595 glycosylation Effects 0.000 description 5
- 238000006206 glycosylation reaction Methods 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 210000003734 kidney Anatomy 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 108020004999 messenger RNA Proteins 0.000 description 5
- 230000010076 replication Effects 0.000 description 5
- 241000894007 species Species 0.000 description 5
- 230000009885 systemic effect Effects 0.000 description 5
- 239000004475 Arginine Substances 0.000 description 4
- 241000701931 Canine parvovirus Species 0.000 description 4
- 235000004035 Cryptotaenia japonica Nutrition 0.000 description 4
- 102220518120 DNA-directed RNA polymerases I and III subunit RPAC1_E6R_mutation Human genes 0.000 description 4
- 102220511796 F-actin-capping protein subunit beta_F26S_mutation Human genes 0.000 description 4
- 102220487360 Guanine nucleotide-binding protein G(i) subunit alpha-1_A54R_mutation Human genes 0.000 description 4
- 102220474905 Insulin-like 3_V43L_mutation Human genes 0.000 description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 4
- 102220638483 Protein PML_K65R_mutation Human genes 0.000 description 4
- 102000007641 Trefoil Factors Human genes 0.000 description 4
- 235000015724 Trifolium pratense Nutrition 0.000 description 4
- 108020005202 Viral DNA Proteins 0.000 description 4
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 4
- 238000011969 continuous reassessment method Methods 0.000 description 4
- 101150044687 crm gene Proteins 0.000 description 4
- 101150024875 hbb2 gene Proteins 0.000 description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
- 230000001976 improved effect Effects 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 238000004806 packaging method and process Methods 0.000 description 4
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 4
- 230000002797 proteolythic effect Effects 0.000 description 4
- 102220332512 rs1555032911 Human genes 0.000 description 4
- 102220297864 rs761846391 Human genes 0.000 description 4
- 210000002363 skeletal muscle cell Anatomy 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 3
- 102100026189 Beta-galactosidase Human genes 0.000 description 3
- 241000701022 Cytomegalovirus Species 0.000 description 3
- 102100023374 Forkhead box protein M1 Human genes 0.000 description 3
- 108020004206 Gamma-glutamyltransferase Proteins 0.000 description 3
- QXPRJQPCFXMCIY-NKWVEPMBSA-N Gly-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN QXPRJQPCFXMCIY-NKWVEPMBSA-N 0.000 description 3
- 101150068639 Hnf4a gene Proteins 0.000 description 3
- 101000907578 Homo sapiens Forkhead box protein M1 Proteins 0.000 description 3
- 101000600434 Homo sapiens Putative uncharacterized protein encoded by MIR7-3HG Proteins 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
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 230000004989 O-glycosylation Effects 0.000 description 3
- 108700026244 Open Reading Frames Proteins 0.000 description 3
- 102000013566 Plasminogen Human genes 0.000 description 3
- 108010051456 Plasminogen Proteins 0.000 description 3
- 102100037401 Putative uncharacterized protein encoded by MIR7-3HG Human genes 0.000 description 3
- 108091081024 Start codon Proteins 0.000 description 3
- 102100028709 Thyroxine-binding globulin Human genes 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 229960001230 asparagine Drugs 0.000 description 3
- 235000009582 asparagine Nutrition 0.000 description 3
- 238000005415 bioluminescence Methods 0.000 description 3
- 230000029918 bioluminescence Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 150000001720 carbohydrates Chemical group 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 238000010494 dissociation reaction Methods 0.000 description 3
- 230000005593 dissociations Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 102000006640 gamma-Glutamyltransferase Human genes 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 229930182817 methionine Natural products 0.000 description 3
- 108010090651 preprocathepsin L Proteins 0.000 description 3
- 235000019833 protease Nutrition 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 230000003584 silencer Effects 0.000 description 3
- 230000014616 translation Effects 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- 101000645498 Alkalihalobacillus pseudofirmus (strain ATCC BAA-2126 / JCM 17055 / OF4) Uncharacterized protein BpOF4_10220 Proteins 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 101001132313 Clostridium pasteurianum 34.2 kDa protein in rubredoxin operon Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 2
- 102000053602 DNA Human genes 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 101000618325 Enterobacteria phage T4 Uncharacterized 12.4 kDa protein in mobB-Gp55 intergenic region Proteins 0.000 description 2
- 101000653284 Enterobacteria phage T4 Uncharacterized 9.4 kDa protein in Gp31-cd intergenic region Proteins 0.000 description 2
- 241000283073 Equus caballus Species 0.000 description 2
- 102100031509 Fibrillin-1 Human genes 0.000 description 2
- 108700007698 Genetic Terminator Regions Proteins 0.000 description 2
- 208000028782 Hereditary disease Diseases 0.000 description 2
- 101001027128 Homo sapiens Fibronectin Proteins 0.000 description 2
- 241000702617 Human parvovirus B19 Species 0.000 description 2
- 102000004867 Hydro-Lyases Human genes 0.000 description 2
- 108090001042 Hydro-Lyases Proteins 0.000 description 2
- 208000013016 Hypoglycemia Diseases 0.000 description 2
- 102000002746 Inhibins Human genes 0.000 description 2
- 108010004250 Inhibins Proteins 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 108010001127 Insulin Receptor Proteins 0.000 description 2
- 102000003746 Insulin Receptor Human genes 0.000 description 2
- 102000004375 Insulin-like growth factor-binding protein 1 Human genes 0.000 description 2
- 108090000957 Insulin-like growth factor-binding protein 1 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
- 102000004882 Lipase Human genes 0.000 description 2
- 108090001060 Lipase Proteins 0.000 description 2
- NPBGTPKLVJEOBE-IUCAKERBSA-N Lys-Arg Chemical compound NCCCC[C@H](N)C(=O)N[C@H](C(O)=O)CCCNC(N)=N NPBGTPKLVJEOBE-IUCAKERBSA-N 0.000 description 2
- 208000024556 Mendelian disease Diseases 0.000 description 2
- 108010071690 Prealbumin Proteins 0.000 description 2
- 101000758676 Pyrococcus woesei Uncharacterized 24.7 kDa protein in gap 5'region Proteins 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 101000890996 Rattus norvegicus Fibronectin Proteins 0.000 description 2
- 102220492283 Replication stress response regulator SDE2_R37K_mutation Human genes 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 102000011409 Transcobalamins Human genes 0.000 description 2
- 108010023603 Transcobalamins Proteins 0.000 description 2
- 102100029290 Transthyretin Human genes 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000001994 activation Methods 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 238000002869 basic local alignment search tool Methods 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000002487 chromatin immunoprecipitation Methods 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- 210000000172 cytosol Anatomy 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000003292 diminished effect Effects 0.000 description 2
- 238000002641 enzyme replacement therapy Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- 230000002218 hypoglycaemic effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000000893 inhibin Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 230000000116 mitigating effect Effects 0.000 description 2
- 238000009126 molecular therapy Methods 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 102220053681 rs727503299 Human genes 0.000 description 2
- 230000009919 sequestration Effects 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000002463 transducing effect Effects 0.000 description 2
- 229910052720 vanadium Inorganic materials 0.000 description 2
- 108700026220 vif Genes Proteins 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- BRPMXFSTKXXNHF-IUCAKERBSA-N (2s)-1-[2-[[(2s)-pyrrolidine-2-carbonyl]amino]acetyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H]1NCCC1 BRPMXFSTKXXNHF-IUCAKERBSA-N 0.000 description 1
- AUXMWYRZQPIXCC-KNIFDHDWSA-N (2s)-2-amino-4-methylpentanoic acid;(2s)-2-aminopropanoic acid Chemical compound C[C@H](N)C(O)=O.CC(C)C[C@H](N)C(O)=O AUXMWYRZQPIXCC-KNIFDHDWSA-N 0.000 description 1
- SULKGYKWHKPPKO-RAJPIYRYSA-N (4s)-4-[[(2r)-2-[[(2s,3r)-2-[[(2s)-4-amino-4-oxo-2-[[(2s)-pyrrolidine-2-carbonyl]amino]butanoyl]amino]-3-hydroxybutanoyl]amino]-3-sulfanylpropanoyl]amino]-5-[[(2s,3s)-1-[[(2r)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2r)-1-[[(2s,3r)-1-[[2-[[(1r)-1-carboxy Chemical compound N([C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CS)C(O)=O)[C@@H](C)O)C(=O)[C@@H]1CCCN1 SULKGYKWHKPPKO-RAJPIYRYSA-N 0.000 description 1
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- NEWKHUASLBMWRE-UHFFFAOYSA-N 2-methyl-6-(phenylethynyl)pyridine Chemical compound CC1=CC=CC(C#CC=2C=CC=CC=2)=N1 NEWKHUASLBMWRE-UHFFFAOYSA-N 0.000 description 1
- LVRVABPNVHYXRT-BQWXUCBYSA-N 52906-92-0 Chemical compound C([C@H](N)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(O)=O)C(C)C)C1=CC=CC=C1 LVRVABPNVHYXRT-BQWXUCBYSA-N 0.000 description 1
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 1
- 241001634120 Adeno-associated virus - 5 Species 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 241000702419 Ambidensovirus Species 0.000 description 1
- 102220483699 Aminopeptidase RNPEPL1_R68A_mutation Human genes 0.000 description 1
- 239000004382 Amylase Substances 0.000 description 1
- 102000004881 Angiotensinogen Human genes 0.000 description 1
- 108090001067 Angiotensinogen Proteins 0.000 description 1
- 101710170876 Antileukoproteinase Proteins 0.000 description 1
- 102100021253 Antileukoproteinase Human genes 0.000 description 1
- 102000004411 Antithrombin III Human genes 0.000 description 1
- 108090000935 Antithrombin III Proteins 0.000 description 1
- 108010071619 Apolipoproteins Proteins 0.000 description 1
- 102000007592 Apolipoproteins Human genes 0.000 description 1
- OMLWNBVRVJYMBQ-YUMQZZPRSA-N Arg-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O OMLWNBVRVJYMBQ-YUMQZZPRSA-N 0.000 description 1
- DGFGDPVSDQPANQ-XGEHTFHBSA-N Arg-Cys-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CCCN=C(N)N)N)O DGFGDPVSDQPANQ-XGEHTFHBSA-N 0.000 description 1
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 1
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 101800001288 Atrial natriuretic factor Proteins 0.000 description 1
- 102400001282 Atrial natriuretic peptide Human genes 0.000 description 1
- 101800001890 Atrial natriuretic peptide Proteins 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 102100030009 Azurocidin Human genes 0.000 description 1
- 101710154607 Azurocidin Proteins 0.000 description 1
- 102100035687 Bile salt-activated lipase Human genes 0.000 description 1
- 101710130200 Bile salt-activated lipase Proteins 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 241000701922 Bovine parvovirus Species 0.000 description 1
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 1
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 1
- 102100036850 C-C motif chemokine 23 Human genes 0.000 description 1
- 125000001433 C-terminal amino-acid group Chemical group 0.000 description 1
- 102100024881 C3 and PZP-like alpha-2-macroglobulin domain-containing protein 8 Human genes 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 206010051093 Cardiopulmonary failure Diseases 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 102000011632 Caseins Human genes 0.000 description 1
- 241001432959 Chernes Species 0.000 description 1
- 241000684559 Chicken parvovirus Species 0.000 description 1
- 102000010792 Chromogranin A Human genes 0.000 description 1
- 108010038447 Chromogranin A Proteins 0.000 description 1
- 102000010791 Chromogranin B Human genes 0.000 description 1
- 108010038439 Chromogranin B Proteins 0.000 description 1
- 108090000746 Chymosin Proteins 0.000 description 1
- 102100039501 Chymotrypsinogen B Human genes 0.000 description 1
- 101710147853 Chymotrypsinogen B Proteins 0.000 description 1
- 102000003780 Clusterin Human genes 0.000 description 1
- 108090000197 Clusterin Proteins 0.000 description 1
- 102100022641 Coagulation factor IX Human genes 0.000 description 1
- 102100037529 Coagulation factor V Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 102000006630 Contactin 2 Human genes 0.000 description 1
- 108010087196 Contactin 2 Proteins 0.000 description 1
- 102400000060 Copeptin Human genes 0.000 description 1
- 101800000115 Copeptin Proteins 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 102000015833 Cystatin Human genes 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
- 101001062538 Danio rerio Follistatin-A Proteins 0.000 description 1
- 102000000541 Defensins Human genes 0.000 description 1
- 108010002069 Defensins Proteins 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 108010015720 Dopamine beta-Hydroxylase Proteins 0.000 description 1
- 108010014258 Elastin Proteins 0.000 description 1
- 102000016942 Elastin Human genes 0.000 description 1
- 241000121268 Erythroparvovirus Species 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108010076282 Factor IX Proteins 0.000 description 1
- 108010014172 Factor V Proteins 0.000 description 1
- 108010054218 Factor VIII Proteins 0.000 description 1
- 102000001690 Factor VIII Human genes 0.000 description 1
- 108010080865 Factor XII Proteins 0.000 description 1
- 102000000429 Factor XII Human genes 0.000 description 1
- 241000701915 Feline panleukopenia virus Species 0.000 description 1
- 241000701925 Feline parvovirus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010049003 Fibrinogen Proteins 0.000 description 1
- 102000008946 Fibrinogen Human genes 0.000 description 1
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 1
- 102000003972 Fibroblast growth factor 7 Human genes 0.000 description 1
- 108090000368 Fibroblast growth factor 8 Proteins 0.000 description 1
- 102100031812 Fibulin-1 Human genes 0.000 description 1
- 101710170731 Fibulin-1 Proteins 0.000 description 1
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 1
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 1
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 1
- 102000029813 Gastric triacylglycerol lipase Human genes 0.000 description 1
- 108090001072 Gastricsin Proteins 0.000 description 1
- 102000004862 Gastrin releasing peptide Human genes 0.000 description 1
- 108090001053 Gastrin releasing peptide Proteins 0.000 description 1
- 102000004878 Gelsolin Human genes 0.000 description 1
- 108090001064 Gelsolin Proteins 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- GPSHCSTUYOQPAI-JHEQGTHGSA-N Glu-Thr-Gly Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(O)=O GPSHCSTUYOQPAI-JHEQGTHGSA-N 0.000 description 1
- 102400000321 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- 102100036264 Glucose-6-phosphatase catalytic subunit 1 Human genes 0.000 description 1
- OVSKVOOUFAKODB-UWVGGRQHSA-N Gly-Arg-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)CN)CCCN=C(N)N OVSKVOOUFAKODB-UWVGGRQHSA-N 0.000 description 1
- FFALDIDGPLUDKV-ZDLURKLDSA-N Gly-Thr-Ser Chemical compound [H]NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O FFALDIDGPLUDKV-ZDLURKLDSA-N 0.000 description 1
- 102000010956 Glypican Human genes 0.000 description 1
- 108050001154 Glypican Proteins 0.000 description 1
- 108050007238 Glypican-1 Proteins 0.000 description 1
- 241001517118 Goose parvovirus Species 0.000 description 1
- 102100039619 Granulocyte colony-stimulating factor 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
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 239000000095 Growth Hormone-Releasing Hormone Substances 0.000 description 1
- 102400001367 Guanylin Human genes 0.000 description 1
- 101800004305 Guanylin Proteins 0.000 description 1
- 108090000481 Heparin Cofactor II Proteins 0.000 description 1
- 102100030500 Heparin cofactor 2 Human genes 0.000 description 1
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101800002879 Histatin-3 Proteins 0.000 description 1
- 102100021628 Histatin-3 Human genes 0.000 description 1
- 101000713081 Homo sapiens C-C motif chemokine 23 Proteins 0.000 description 1
- 101000930910 Homo sapiens Glucose-6-phosphatase catalytic subunit 1 Proteins 0.000 description 1
- 101000746367 Homo sapiens Granulocyte colony-stimulating factor Proteins 0.000 description 1
- 101001034652 Homo sapiens Insulin-like growth factor 1 receptor Proteins 0.000 description 1
- 101000599951 Homo sapiens Insulin-like growth factor I Proteins 0.000 description 1
- 101001044927 Homo sapiens Insulin-like growth factor-binding protein 3 Proteins 0.000 description 1
- 241001135569 Human adenovirus 5 Species 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 108700002232 Immediate-Early Genes Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 108090000964 Insulin-like growth factor binding protein 2 Proteins 0.000 description 1
- 102100022710 Insulin-like growth factor-binding protein 2 Human genes 0.000 description 1
- 102100022708 Insulin-like growth factor-binding protein 3 Human genes 0.000 description 1
- 102000004883 Insulin-like growth factor-binding protein 6 Human genes 0.000 description 1
- 108090001014 Insulin-like growth factor-binding protein 6 Proteins 0.000 description 1
- 108010028750 Integrin-Binding Sialoprotein Proteins 0.000 description 1
- 102000016921 Integrin-Binding Sialoprotein Human genes 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- 241000121270 Iteradensovirus Species 0.000 description 1
- 108010077861 Kininogens Proteins 0.000 description 1
- 102000010631 Kininogens Human genes 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-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
- 108010059801 Lactase-Phlorizin Hydrolase Proteins 0.000 description 1
- 108010063045 Lactoferrin Proteins 0.000 description 1
- 102000010445 Lactoferrin Human genes 0.000 description 1
- 241000222722 Leishmania <genus> Species 0.000 description 1
- KSZCCRIGNVSHFH-UWVGGRQHSA-N Leu-Arg-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O KSZCCRIGNVSHFH-UWVGGRQHSA-N 0.000 description 1
- PPBKJAQJAUHZKX-SRVKXCTJSA-N Leu-Cys-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CS)C(=O)N[C@H](C(O)=O)CC(C)C PPBKJAQJAUHZKX-SRVKXCTJSA-N 0.000 description 1
- 102000004058 Leukemia inhibitory factor Human genes 0.000 description 1
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- ZUGVARDEGWMMLK-SRVKXCTJSA-N Lys-Ser-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCCCN ZUGVARDEGWMMLK-SRVKXCTJSA-N 0.000 description 1
- 102220611856 Lysosomal alpha-glucosidase_V949D_mutation Human genes 0.000 description 1
- 208000033868 Lysosomal disease Diseases 0.000 description 1
- 102100033468 Lysozyme C Human genes 0.000 description 1
- 108050000633 Lysozyme C Proteins 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 108010072582 Matrilin Proteins Proteins 0.000 description 1
- 102000055008 Matrilin Proteins Human genes 0.000 description 1
- 108090000855 Matrilysin Proteins 0.000 description 1
- 102000004318 Matrilysin Human genes 0.000 description 1
- 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 description 1
- 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 description 1
- 102400001132 Melanin-concentrating hormone Human genes 0.000 description 1
- 101800002739 Melanin-concentrating hormone Proteins 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 102100026262 Metalloproteinase inhibitor 2 Human genes 0.000 description 1
- 108050006602 Metalloproteinase inhibitor 2 Proteins 0.000 description 1
- 102100030335 Midkine Human genes 0.000 description 1
- 108010092801 Midkine Proteins 0.000 description 1
- 102000014171 Milk Proteins Human genes 0.000 description 1
- 108010011756 Milk Proteins Proteins 0.000 description 1
- 102400001357 Motilin Human genes 0.000 description 1
- 101800002372 Motilin Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241001503699 Muscovy duck parvovirus Species 0.000 description 1
- NSTPXGARCQOSAU-VIFPVBQESA-N N-formyl-L-phenylalanine Chemical compound O=CN[C@H](C(=O)O)CC1=CC=CC=C1 NSTPXGARCQOSAU-VIFPVBQESA-N 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 108010026626 Neuroendocrine Secretory Protein 7B2 Proteins 0.000 description 1
- 101710151475 Neuroendocrine convertase 2 Proteins 0.000 description 1
- 102100037732 Neuroendocrine convertase 2 Human genes 0.000 description 1
- 102100036248 Neuroendocrine protein 7B2 Human genes 0.000 description 1
- 108020004485 Nonsense Codon Proteins 0.000 description 1
- 102000004140 Oncostatin M Human genes 0.000 description 1
- 108090000630 Oncostatin M Proteins 0.000 description 1
- 108010077077 Osteonectin Proteins 0.000 description 1
- 102000009890 Osteonectin Human genes 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 102000052651 Pancreatic hormone Human genes 0.000 description 1
- 101800001268 Pancreatic hormone Proteins 0.000 description 1
- 101710126321 Pancreatic trypsin inhibitor Proteins 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 241000701945 Parvoviridae Species 0.000 description 1
- 108010047320 Pepsinogen A Proteins 0.000 description 1
- 102000034255 Pepsinogen C Human genes 0.000 description 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- JEGFCFLCRSJCMA-IHRRRGAJSA-N Phe-Arg-Ser Chemical compound C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CO)C(=O)O)N JEGFCFLCRSJCMA-IHRRRGAJSA-N 0.000 description 1
- 102100040402 Phlorizin hydrolase Human genes 0.000 description 1
- 102100037883 Phospholipase B1, membrane-associated Human genes 0.000 description 1
- 108010058864 Phospholipases A2 Proteins 0.000 description 1
- 108090000113 Plasma Kallikrein Proteins 0.000 description 1
- 102100034869 Plasma kallikrein Human genes 0.000 description 1
- 101710183733 Plasma serine protease inhibitor Proteins 0.000 description 1
- 102100024078 Plasma serine protease inhibitor Human genes 0.000 description 1
- 108010022233 Plasminogen Activator Inhibitor 1 Proteins 0.000 description 1
- 108010001014 Plasminogen Activators Proteins 0.000 description 1
- 102000001938 Plasminogen Activators Human genes 0.000 description 1
- 102100039418 Plasminogen activator inhibitor 1 Human genes 0.000 description 1
- 108010045766 Platelet Glycoprotein GPIb-IX Complex Proteins 0.000 description 1
- 102000023159 Platelet Glycoprotein GPIb-IX Complex Human genes 0.000 description 1
- 102100030582 Platelet factor 4 variant Human genes 0.000 description 1
- 101710198959 Platelet factor 4 variant Proteins 0.000 description 1
- 101800001717 Preptin Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 108010050808 Procollagen Proteins 0.000 description 1
- 102100038931 Proenkephalin-A Human genes 0.000 description 1
- 102000003946 Prolactin Human genes 0.000 description 1
- 108010057464 Prolactin Proteins 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 108010005642 Properdin Proteins 0.000 description 1
- 102100038567 Properdin Human genes 0.000 description 1
- 102100034949 Prorelaxin H2 Human genes 0.000 description 1
- 101710142655 Prorelaxin H2 Proteins 0.000 description 1
- 102100036197 Prosaposin Human genes 0.000 description 1
- 101710152403 Prosaposin Proteins 0.000 description 1
- 102100035703 Prostatic acid phosphatase Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 102000009572 RNA Polymerase II Human genes 0.000 description 1
- 108010009460 RNA Polymerase II Proteins 0.000 description 1
- 208000035977 Rare disease Diseases 0.000 description 1
- 101100286581 Rattus norvegicus Igf2 gene Proteins 0.000 description 1
- 102000015338 Seminal Plasma Proteins Human genes 0.000 description 1
- 108010064603 Seminal Plasma Proteins Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000054727 Serum Amyloid A Human genes 0.000 description 1
- 101710190759 Serum amyloid A protein Proteins 0.000 description 1
- 108020004682 Single-Stranded DNA Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 101710142969 Somatoliberin Proteins 0.000 description 1
- 102100022831 Somatoliberin Human genes 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 102000014284 Statherin Human genes 0.000 description 1
- 108050003162 Statherin Proteins 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 108700005078 Synthetic Genes Proteins 0.000 description 1
- 108700026226 TATA Box Proteins 0.000 description 1
- GXDLGHLJTHMDII-WISUUJSJSA-N Thr-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](CO)C(O)=O GXDLGHLJTHMDII-WISUUJSJSA-N 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102000002262 Thromboplastin Human genes 0.000 description 1
- 108010046722 Thrombospondin 1 Proteins 0.000 description 1
- 102100036034 Thrombospondin-1 Human genes 0.000 description 1
- 102000006601 Thymidine Kinase Human genes 0.000 description 1
- 108020004440 Thymidine kinase Proteins 0.000 description 1
- 108010034949 Thyroglobulin Proteins 0.000 description 1
- 102000009843 Thyroglobulin Human genes 0.000 description 1
- 102100029530 Thyrotropin subunit beta Human genes 0.000 description 1
- 101710087584 Thyrotropin subunit beta Proteins 0.000 description 1
- 108010000259 Thyroxine-Binding Globulin Proteins 0.000 description 1
- 102100030951 Tissue factor pathway inhibitor Human genes 0.000 description 1
- 102000014034 Transcortin Human genes 0.000 description 1
- 108010011095 Transcortin Proteins 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 108010027252 Trypsinogen Proteins 0.000 description 1
- 102000018690 Trypsinogen Human genes 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
- 101150049278 US20 gene Proteins 0.000 description 1
- 102100037697 Uridylate-specific endoribonuclease Human genes 0.000 description 1
- 102100040613 Uromodulin Human genes 0.000 description 1
- 108010027007 Uromodulin Proteins 0.000 description 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 description 1
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
- 108010004977 Vasopressins Proteins 0.000 description 1
- 102000002852 Vasopressins Human genes 0.000 description 1
- 102100035140 Vitronectin Human genes 0.000 description 1
- 108010031318 Vitronectin Proteins 0.000 description 1
- 102000052547 Wnt-1 Human genes 0.000 description 1
- 108700020987 Wnt-1 Proteins 0.000 description 1
- 101000890995 Xenopus laevis Fibronectin Proteins 0.000 description 1
- 235000008529 Ziziphus vulgaris Nutrition 0.000 description 1
- 244000126002 Ziziphus vulgaris Species 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 208000037919 acquired disease Diseases 0.000 description 1
- 108700015342 adenovirus terminal Proteins 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 229960005348 antithrombin iii Drugs 0.000 description 1
- 108010091092 arginyl-glycyl-proline Proteins 0.000 description 1
- 108010068380 arginylarginine Proteins 0.000 description 1
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 210000003123 bronchiole Anatomy 0.000 description 1
- NSQLIUXCMFBZME-MPVJKSABSA-N carperitide Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 NSQLIUXCMFBZME-MPVJKSABSA-N 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000003541 chymotrypsin inhibitor Substances 0.000 description 1
- 238000012411 cloning technique Methods 0.000 description 1
- 229940105774 coagulation factor ix Drugs 0.000 description 1
- 229940105778 coagulation factor viii Drugs 0.000 description 1
- 102000005311 colipase Human genes 0.000 description 1
- 108020002632 colipase Proteins 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 108050004038 cystatin Proteins 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 210000003674 cytoplasmic vesicle Anatomy 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 210000000188 diaphragm Anatomy 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229920002549 elastin Polymers 0.000 description 1
- 210000003060 endolymph Anatomy 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229940012952 fibrinogen Drugs 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 108010091264 gastric triacylglycerol lipase Proteins 0.000 description 1
- PUBCCFNQJQKCNC-XKNFJVFFSA-N gastrin-releasingpeptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)C1=CNC=N1 PUBCCFNQJQKCNC-XKNFJVFFSA-N 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 208000016361 genetic disease Diseases 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 108010050848 glycylleucine Proteins 0.000 description 1
- 210000002149 gonad Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000000122 growth hormone Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 210000002064 heart cell Anatomy 0.000 description 1
- MGLKKQHURMLFDS-ZMASWNFJSA-N histatin 3 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(O)C=C1 MGLKKQHURMLFDS-ZMASWNFJSA-N 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 102000045742 human FN1 Human genes 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 230000033444 hydroxylation Effects 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 230000003345 hyperglycaemic effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000012212 insulator Substances 0.000 description 1
- 229940068935 insulin-like growth factor 2 Drugs 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 210000000738 kidney tubule Anatomy 0.000 description 1
- 208000035157 late-onset glycogen storage disease due to acid maltase deficiency Diseases 0.000 description 1
- 108010013555 lipoprotein-associated coagulation inhibitor Proteins 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 101150054032 lspA gene Proteins 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 229940010004 lysine / phenylalanine Drugs 0.000 description 1
- 102000043253 matrix Gla protein Human genes 0.000 description 1
- 108010057546 matrix Gla protein Proteins 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- ORRDHOMWDPJSNL-UHFFFAOYSA-N melanin concentrating hormone Chemical compound N1C(=O)C(C(C)C)NC(=O)C(CCCNC(N)=N)NC(=O)CNC(=O)C(C(C)C)NC(=O)C(CCSC)NC(=O)C(NC(=O)C(CCCNC(N)=N)NC(=O)C(NC(=O)C(NC(=O)C(N)CC(O)=O)C(C)O)CCSC)CSSCC(C(=O)NC(CC=2C3=CC=CC=C3NC=2)C(=O)NC(CCC(O)=O)C(=O)NC(C(C)C)C(O)=O)NC(=O)C2CCCN2C(=O)C(CCCNC(N)=N)NC(=O)C1CC1=CC=C(O)C=C1 ORRDHOMWDPJSNL-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 235000021239 milk protein Nutrition 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 230000004220 muscle function Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- SQMWSBKSHWARHU-SDBHATRESA-N n6-cyclopentyladenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(NC3CCCC3)=C2N=C1 SQMWSBKSHWARHU-SDBHATRESA-N 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 108010008217 nidogen Proteins 0.000 description 1
- 229910052758 niobium Inorganic materials 0.000 description 1
- 230000037434 nonsense mutation Effects 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000004025 pancreas hormone Substances 0.000 description 1
- 229940032957 pancreatic hormone Drugs 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- LQRJAEQXMSMEDP-XCHBZYMASA-N peptide a Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)NCCCC[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)C(\NC(=O)[C@@H](CCCCN)NC(=O)CNC(C)=O)=C/C=1C=CC=CC=1)C(N)=O)C(=O)C(\NC(=O)[C@@H](CCCCN)NC(=O)CNC(C)=O)=C\C1=CC=CC=C1 LQRJAEQXMSMEDP-XCHBZYMASA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 108010045797 placental protein 11 Proteins 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229940127126 plasminogen activator Drugs 0.000 description 1
- 102000005162 pleiotrophin Human genes 0.000 description 1
- 230000036178 pleiotropy Effects 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 230000004481 post-translational protein modification 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
- 230000002028 premature Effects 0.000 description 1
- 108010051421 procholecystokinin Proteins 0.000 description 1
- 108010041071 proenkephalin Proteins 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 229940097325 prolactin Drugs 0.000 description 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 108010043671 prostatic acid phosphatase Proteins 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000012846 protein folding Effects 0.000 description 1
- 230000018883 protein targeting Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 239000013647 rAAV8 vector Substances 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 210000005163 right hepatic lobe Anatomy 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 150000003354 serine derivatives Chemical class 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012385 systemic delivery Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960002175 thyroglobulin Drugs 0.000 description 1
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 108010047303 von Willebrand Factor Proteins 0.000 description 1
- 102100036537 von Willebrand factor Human genes 0.000 description 1
- 229960001134 von willebrand factor Drugs 0.000 description 1
- 235000021246 κ-casein Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/62—Insulins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/78—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
- C12N9/2405—Glucanases
- C12N9/2408—Glucanases acting on alpha -1,4-glucosidic bonds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
-
- 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
- C12N2810/00—Vectors comprising a targeting moiety
- C12N2810/50—Vectors comprising as targeting moiety peptide derived from defined protein
- C12N2810/80—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates
- C12N2810/85—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates mammalian
- C12N2810/851—Vectors comprising as targeting moiety peptide derived from defined protein from vertebrates mammalian from growth factors; from growth regulators
-
- 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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
-
- 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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/38—Vector systems having a special element relevant for transcription being a stuffer
-
- 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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/42—Vector systems having a special element relevant for transcription being an intron or intervening sequence for splicing and/or stability of RNA
-
- 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
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/50—Vector systems having a special element relevant for transcription regulating RNA stability, not being an intron, e.g. poly A signal
-
- 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)
- C12Y302/0102—Alpha-glucosidase (3.2.1.20)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Biophysics (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Microbiology (AREA)
- Diabetes (AREA)
- Virology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Endocrinology (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962937583P | 2019-11-19 | 2019-11-19 | |
| US201962937556P | 2019-11-19 | 2019-11-19 | |
| US202063023570P | 2020-05-12 | 2020-05-12 | |
| PCT/US2020/061223 WO2021102107A1 (en) | 2019-11-19 | 2020-11-19 | Therapeutic adeno-associated virus comprising liver-specific promoters for treating pompe disease and lysosomal disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL293068A true IL293068A (en) | 2022-07-01 |
Family
ID=75981066
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL293068A IL293068A (en) | 2019-11-19 | 2020-11-19 | Therapeutic adeno-associated virus comprising liver-specific promoters for treating pompe disease and lysosomal disorders |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20230038520A1 (enExample) |
| EP (1) | EP4061946A4 (enExample) |
| JP (1) | JP2023503046A (enExample) |
| KR (1) | KR20220098384A (enExample) |
| CN (1) | CN116096895A (enExample) |
| AU (1) | AU2020388634A1 (enExample) |
| CA (1) | CA3159018A1 (enExample) |
| IL (1) | IL293068A (enExample) |
| MX (1) | MX2022005916A (enExample) |
| PH (1) | PH12022551229A1 (enExample) |
| WO (1) | WO2021102107A1 (enExample) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2022513067A (ja) * | 2018-11-16 | 2022-02-07 | アスクレピオス バイオファーマシューティカル， インコーポレイテッド | ポンペ病を処置するための治療用アデノ随伴ウイルス |
| WO2023288301A1 (en) * | 2021-07-15 | 2023-01-19 | Cornell University | Engineered biomolecules for nutrient reprogramming |
| AR126877A1 (es) * | 2021-08-25 | 2023-11-22 | Canbridge Pharmaceuticals Inc | PARTÍCULAS DE AAV QUE COMPRENDEN UNA PROTEÍNA DE LA CÁPSIDE HEPATOTRÓPICA Y a-GLUCOSIDASA ÁCIDA (GAA) Y SU USO PARA TRATAR LA ENFERMEDAD DE POMPE |
| CA3229998A1 (en) * | 2021-08-25 | 2023-03-02 | Canbridge Pharmaceuticals, Inc. | Aav particles comprising a liver-tropic capsid protein and alpha-galactosidase and their use to treat fabry disease |
| WO2023139496A1 (en) * | 2022-01-21 | 2023-07-27 | Pfizer Inc. | Gene therapy for gaucher disease |
| CA3250992A1 (en) * | 2022-02-03 | 2023-08-10 | Astellas Gene Therapies, Inc. | COMPOSITIONS AND METHODS FOR AN IMPROVED TREATMENT OF POMPE DISEASE |
| CN119095612A (zh) * | 2022-02-25 | 2024-12-06 | 阿斯克肋匹奥生物制药公司 | 用于在长期停止gaa酶替代疗法的情况下治疗庞贝病的治疗性腺相关病毒 |
| WO2023172975A1 (en) * | 2022-03-08 | 2023-09-14 | University Of Massachusetts | Methods of raav packaging |
| US20250213726A1 (en) * | 2022-03-18 | 2025-07-03 | Asklepios Biopharmaceutical, Inc. | Therapeutic adeno-associated virus using codon optimized nucleic acid encoding alpha-glucosidase (gaa) for treating pompe disease, with signal peptide modifications |
| WO2024055272A1 (zh) * | 2022-09-16 | 2024-03-21 | 复旦大学附属中山医院 | 能高效表达目的基因的mRNA载体系统、其构建及应用 |
| WO2024212961A1 (en) * | 2023-04-10 | 2024-10-17 | Skyline Therapeutics (Shanghai) Co., Ltd. | Recombinant aav for the gene therapy of pompe disease |
| CN121358865A (zh) * | 2023-04-20 | 2026-01-16 | 阿斯克生物公司 | 肝脏特异性调控核酸序列 |
| KR20240159745A (ko) | 2023-04-28 | 2024-11-06 | 아주대학교산학협력단 | 유산균 유래 nadh 산화효소를 이용한 비알코올성 지방간염의 유전자 치료제 |
| WO2025018822A1 (ko) * | 2023-07-20 | 2025-01-23 | 제닉스큐어 주식회사 | 라포라병을 예방 또는 치료하기 위한 재조합 아데노 연관 바이러스 및 이를 포함하는 약학적 조성물 |
| KR102814185B1 (ko) * | 2023-07-20 | 2025-06-12 | 제닉스큐어 주식회사 | 라포라병을 예방 또는 치료하기 위한 재조합 아데노 연관 바이러스 및 이를 포함하는 약학적 조성물 |
| IL326018A (en) * | 2023-07-28 | 2026-03-01 | Regeneron Pharma | Introduction of anti-TFR:GAA and anti-CD63:GAA for the treatment of Pompe disease |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2001266740A1 (en) * | 2000-06-06 | 2001-12-17 | Genelabs Technologies, Inc. | Promoters for regulated gene expression |
| ES2371913T3 (es) * | 2003-01-22 | 2012-01-11 | Duke University | Constructos mejorados para expresar polipéptidos lisosomales. |
| US7521211B2 (en) * | 2005-04-05 | 2009-04-21 | Regeneron Pharmaceuticals, Inc | IGF-1 and IGF-2 chimeric polypeptides and therapeutic uses thereof |
| EP2162540A2 (en) * | 2007-05-22 | 2010-03-17 | Amgen Inc. | Compositions and methods for producing bioactive fusion proteins |
| 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 |
| AU2010366066B2 (en) * | 2010-12-22 | 2016-01-14 | Fondazione Telethon | Therapeutic strategies to treat CNS pathology in mucopolysaccharidoses |
| MX2013012345A (es) * | 2011-04-22 | 2015-05-07 | Genzyme Corp | Alfa glucosidasa acida modificada con procesamiento acelerado. |
| KR102423442B1 (ko) * | 2015-12-11 | 2022-07-20 | 캘리포니아 인스티튜트 오브 테크놀로지 | 아데노-관련 바이러스를 지시하기 위한 타겟팅 펩타이드 |
| EP3293260A1 (en) * | 2016-09-12 | 2018-03-14 | Genethon | Acid-alpha glucosidase variants and uses thereof |
| EP3293259A1 (en) * | 2016-09-12 | 2018-03-14 | Genethon | Acid-alpha glucosidase variants and uses thereof |
| CN111936621B (zh) * | 2018-02-05 | 2025-05-13 | 奥登茨治疗公司 | 转录调控元件和它的用途 |
| US12258597B2 (en) * | 2018-02-07 | 2025-03-25 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for therapeutic protein delivery |
| BR112020021962A2 (pt) * | 2018-04-30 | 2021-01-26 | Amicus Therapeutics, Inc. | construtos para terapia gênica e métodos de uso |
| JP2022513067A (ja) * | 2018-11-16 | 2022-02-07 | アスクレピオス バイオファーマシューティカル， インコーポレイテッド | ポンペ病を処置するための治療用アデノ随伴ウイルス |
-
2020
- 2020-11-19 KR KR1020227020169A patent/KR20220098384A/ko active Pending
- 2020-11-19 JP JP2022529007A patent/JP2023503046A/ja active Pending
- 2020-11-19 PH PH1/2022/551229A patent/PH12022551229A1/en unknown
- 2020-11-19 CA CA3159018A patent/CA3159018A1/en active Pending
- 2020-11-19 EP EP20890917.6A patent/EP4061946A4/en active Pending
- 2020-11-19 AU AU2020388634A patent/AU2020388634A1/en active Pending
- 2020-11-19 WO PCT/US2020/061223 patent/WO2021102107A1/en not_active Ceased
- 2020-11-19 MX MX2022005916A patent/MX2022005916A/es unknown
- 2020-11-19 IL IL293068A patent/IL293068A/en unknown
- 2020-11-19 US US17/778,175 patent/US20230038520A1/en active Pending
- 2020-11-19 CN CN202080093548.9A patent/CN116096895A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| US20230038520A1 (en) | 2023-02-09 |
| MX2022005916A (es) | 2022-08-04 |
| CN116096895A (zh) | 2023-05-09 |
| EP4061946A1 (en) | 2022-09-28 |
| EP4061946A4 (en) | 2024-03-06 |
| PH12022551229A1 (en) | 2023-07-31 |
| JP2023503046A (ja) | 2023-01-26 |
| TW202132570A (zh) | 2021-09-01 |
| KR20220098384A (ko) | 2022-07-12 |
| CA3159018A1 (en) | 2021-05-27 |
| AU2020388634A1 (en) | 2022-06-23 |
| WO2021102107A1 (en) | 2021-05-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20230038520A1 (en) | Therapeutic adeno-associated virus comprising liver-specific promoters for treating pompe disease and lysosomal disorders | |
| JP7667122B2 (ja) | 酸性αグルコシダーゼ変異体及びその使用 | |
| US20220054656A1 (en) | Therapeutic adeno-associated virus for treating pompe disease | |
| JP7245155B2 (ja) | 酸性αグルコシダーゼ変異体及びその使用 | |
| US20220133906A1 (en) | Vectors comprising a nucleic acid encoding lysosomal enzymes fused to a lysosomal teargeting sequence | |
| JP7719060B2 (ja) | キメラポリペプチド及びその使用 | |
| US20220331408A1 (en) | Treatment of glycogen storage disease (gsd) | |
| US20250163457A1 (en) | Therapeutic adeno-associated virus for treating pompe disease with long term cessation of gaa enzyme replacement therapy | |
| JP2025510017A (ja) | シグナルペプチド改変を有する、ポンペ病を処置するためのアルファ－グルコシダーゼ（ｇａａ）をコードするコドン最適化核酸を使用する治療用アデノ随伴ウイルス | |
| TWI920044B (zh) | 用於治療龐貝症及溶酶體病症之包含肝特異性啟動子之治療性腺相關病毒 | |
| HK40087843A (zh) | 用於治疗庞贝氏病和溶酶体紊乱的包含肝特异性启动子的治疗性腺相关病毒 | |
| JP2023512043A (ja) | ムコ多糖症ｉｖａの治療 | |
| TW202526024A (zh) | 用於治療龐貝症之具有異源訊號肽之利用編碼α－葡萄糖苷酶（ＧＡＡ）之核酸之治療性腺相關病毒 | |
| HK40059690A (en) | Therapeutic adeno-associated virus for treating pompe disease | |
| WO2024241176A1 (en) | Recombinant aav vectors and methods for treatment of diseases with central nervous system disorders |