TW202128733A - 使用肝特異性基因療法載體之遺傳性血管性水腫的治療 - Google Patents
使用肝特異性基因療法載體之遺傳性血管性水腫的治療 Download PDFInfo
- Publication number
- TW202128733A TW202128733A TW109139830A TW109139830A TW202128733A TW 202128733 A TW202128733 A TW 202128733A TW 109139830 A TW109139830 A TW 109139830A TW 109139830 A TW109139830 A TW 109139830A TW 202128733 A TW202128733 A TW 202128733A
- Authority
- TW
- Taiwan
- Prior art keywords
- aav
- c1ei
- vector
- vector construct
- seq
- Prior art date
Links
- 206010019860 Hereditary angioedema Diseases 0.000 title claims abstract description 88
- 239000013598 vector Substances 0.000 title claims description 229
- 210000004185 liver Anatomy 0.000 title claims description 92
- 238000011282 treatment Methods 0.000 title description 59
- 238000001415 gene therapy Methods 0.000 title description 12
- 238000000034 method Methods 0.000 claims abstract description 95
- 239000000203 mixture Substances 0.000 claims abstract description 35
- 229940009550 c1 esterase inhibitor Drugs 0.000 claims abstract description 28
- 108090000623 proteins and genes Proteins 0.000 claims description 205
- 239000002245 particle Substances 0.000 claims description 157
- 210000004027 cell Anatomy 0.000 claims description 156
- 102000004169 proteins and genes Human genes 0.000 claims description 139
- 239000002773 nucleotide Substances 0.000 claims description 128
- 125000003729 nucleotide group Chemical group 0.000 claims description 128
- 150000007523 nucleic acids Chemical group 0.000 claims description 125
- 102000039446 nucleic acids Human genes 0.000 claims description 99
- 108020004707 nucleic acids Proteins 0.000 claims description 99
- 210000000234 capsid Anatomy 0.000 claims description 55
- 230000001105 regulatory effect Effects 0.000 claims description 50
- 241000238631 Hexapoda Species 0.000 claims description 38
- 239000003623 enhancer Substances 0.000 claims description 37
- 230000014509 gene expression Effects 0.000 claims description 36
- 241000124008 Mammalia Species 0.000 claims description 31
- 241001634120 Adeno-associated virus - 5 Species 0.000 claims description 29
- 108091092195 Intron Proteins 0.000 claims description 29
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 29
- 102000055157 Complement C1 Inhibitor Human genes 0.000 claims description 28
- 239000008194 pharmaceutical composition Substances 0.000 claims description 28
- 238000004519 manufacturing process Methods 0.000 claims description 27
- 108090000565 Capsid Proteins Proteins 0.000 claims description 25
- 102100023321 Ceruloplasmin Human genes 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 25
- 239000012634 fragment Substances 0.000 claims description 25
- 238000013518 transcription Methods 0.000 claims description 23
- 230000035897 transcription Effects 0.000 claims description 22
- 150000001413 amino acids Chemical class 0.000 claims description 21
- 241000702421 Dependoparvovirus Species 0.000 claims description 20
- 108050007539 Plasma protease C1 inhibitor Proteins 0.000 claims description 20
- 239000003246 corticosteroid Substances 0.000 claims description 20
- 208000024891 symptom Diseases 0.000 claims description 20
- 210000004369 blood Anatomy 0.000 claims description 19
- 239000008280 blood Substances 0.000 claims description 19
- 108010000521 Human Growth Hormone Proteins 0.000 claims description 14
- 102000002265 Human Growth Hormone Human genes 0.000 claims description 14
- 239000000854 Human Growth Hormone Substances 0.000 claims description 14
- 230000007812 deficiency Effects 0.000 claims description 14
- 230000002103 transcriptional effect Effects 0.000 claims description 14
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 13
- 230000008488 polyadenylation Effects 0.000 claims description 13
- 108700028146 Genetic Enhancer Elements Proteins 0.000 claims description 12
- 239000002753 trypsin inhibitor Substances 0.000 claims description 12
- 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 11
- 206010030113 Oedema Diseases 0.000 claims description 11
- 210000004962 mammalian cell Anatomy 0.000 claims description 11
- 230000010076 replication Effects 0.000 claims description 11
- 238000002560 therapeutic procedure Methods 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 9
- 230000001965 increasing effect Effects 0.000 claims description 8
- 241000282693 Cercopithecidae Species 0.000 claims description 7
- 241000202702 Adeno-associated virus - 3 Species 0.000 claims description 6
- 241001504519 Papio ursinus Species 0.000 claims description 6
- 238000007920 subcutaneous administration Methods 0.000 claims description 6
- 230000010415 tropism Effects 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 238000010276 construction Methods 0.000 claims description 3
- 239000007900 aqueous suspension Substances 0.000 claims description 2
- 102000013918 Apolipoproteins E Human genes 0.000 claims 3
- 108010025628 Apolipoproteins E Proteins 0.000 claims 3
- 241000702423 Adeno-associated virus - 2 Species 0.000 claims 1
- 239000013608 rAAV vector Substances 0.000 claims 1
- 108091006086 inhibitor proteins Proteins 0.000 abstract description 2
- 235000018102 proteins Nutrition 0.000 description 125
- 241000700605 Viruses Species 0.000 description 76
- 239000013607 AAV vector Substances 0.000 description 57
- 241000699670 Mus sp. Species 0.000 description 56
- 108020004414 DNA Proteins 0.000 description 43
- 230000001225 therapeutic effect Effects 0.000 description 37
- 108020004705 Codon Proteins 0.000 description 30
- 239000003001 serine protease inhibitor Substances 0.000 description 29
- 102000040430 polynucleotide Human genes 0.000 description 28
- 108091033319 polynucleotide Proteins 0.000 description 28
- 239000002157 polynucleotide Substances 0.000 description 28
- 210000002381 plasma Anatomy 0.000 description 26
- 241000701447 unidentified baculovirus Species 0.000 description 25
- 101001081555 Homo sapiens Plasma protease C1 inhibitor Proteins 0.000 description 24
- 238000009472 formulation Methods 0.000 description 24
- 238000001476 gene delivery Methods 0.000 description 21
- 108091026890 Coding region Proteins 0.000 description 20
- 229940024606 amino acid Drugs 0.000 description 19
- 235000001014 amino acid Nutrition 0.000 description 19
- 108090000765 processed proteins & peptides Proteins 0.000 description 19
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 18
- 238000003556 assay Methods 0.000 description 18
- 230000000694 effects Effects 0.000 description 18
- 229940088950 c1 esterase inhibitor (human) Drugs 0.000 description 17
- 210000003494 hepatocyte Anatomy 0.000 description 17
- 102100036475 Alanine aminotransferase 1 Human genes 0.000 description 16
- 108010082126 Alanine transaminase Proteins 0.000 description 16
- 101000823116 Homo sapiens Alpha-1-antitrypsin Proteins 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 16
- 210000002706 plastid Anatomy 0.000 description 16
- 229920001184 polypeptide Polymers 0.000 description 16
- 102000004196 processed proteins & peptides Human genes 0.000 description 16
- 230000006870 function Effects 0.000 description 15
- 108091034057 RNA (poly(A)) Proteins 0.000 description 14
- 230000001154 acute effect Effects 0.000 description 14
- 239000003795 chemical substances by application Substances 0.000 description 14
- 238000005516 engineering process Methods 0.000 description 14
- 101150044789 Cap gene Proteins 0.000 description 13
- 101710196289 Eukaryotic translation initiation factor 2-alpha kinase 1 Proteins 0.000 description 13
- 241000125945 Protoparvovirus Species 0.000 description 13
- 241000701161 unidentified adenovirus Species 0.000 description 13
- 238000000338 in vitro Methods 0.000 description 12
- 230000008728 vascular permeability Effects 0.000 description 11
- 239000003981 vehicle Substances 0.000 description 11
- 230000003612 virological effect Effects 0.000 description 11
- 108700010070 Codon Usage Proteins 0.000 description 10
- 108700040183 Complement C1 Inhibitor Proteins 0.000 description 10
- 102000008847 Serpin Human genes 0.000 description 10
- 108050000761 Serpin Proteins 0.000 description 10
- 230000000692 anti-sense effect Effects 0.000 description 10
- 229960001334 corticosteroids Drugs 0.000 description 10
- 238000011156 evaluation Methods 0.000 description 10
- 208000015181 infectious disease Diseases 0.000 description 10
- 230000000069 prophylactic effect Effects 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 10
- 239000013603 viral vector Substances 0.000 description 10
- 238000010361 transduction Methods 0.000 description 9
- 230000026683 transduction Effects 0.000 description 9
- 241001655883 Adeno-associated virus - 1 Species 0.000 description 8
- 102000001554 Hemoglobins Human genes 0.000 description 8
- 108010054147 Hemoglobins Proteins 0.000 description 8
- 108091081021 Sense strand Proteins 0.000 description 8
- 108010006025 bovine growth hormone Proteins 0.000 description 8
- 231100000673 dose–response relationship Toxicity 0.000 description 8
- 231100000304 hepatotoxicity Toxicity 0.000 description 8
- 238000003364 immunohistochemistry Methods 0.000 description 8
- 230000000670 limiting effect Effects 0.000 description 8
- 150000002632 lipids Chemical class 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 241000972680 Adeno-associated virus - 6 Species 0.000 description 7
- 230000004913 activation Effects 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- -1 cells Substances 0.000 description 7
- 238000001514 detection method Methods 0.000 description 7
- 102000051631 human SERPINA1 Human genes 0.000 description 7
- 210000005229 liver cell Anatomy 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- 241000580270 Adeno-associated virus - 4 Species 0.000 description 6
- 102000053602 DNA Human genes 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 101150097162 SERPING1 gene Proteins 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 108700005077 Viral Genes Proteins 0.000 description 6
- 230000004071 biological effect Effects 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000003780 insertion Methods 0.000 description 6
- 230000037431 insertion Effects 0.000 description 6
- 230000001124 posttranscriptional effect Effects 0.000 description 6
- 230000014616 translation Effects 0.000 description 6
- 238000011144 upstream manufacturing Methods 0.000 description 6
- 241001164825 Adeno-associated virus - 8 Species 0.000 description 5
- 108091029430 CpG site Proteins 0.000 description 5
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 5
- 101000889990 Homo sapiens Apolipoprotein(a) Proteins 0.000 description 5
- 102000008100 Human Serum Albumin Human genes 0.000 description 5
- 108091006905 Human Serum Albumin Proteins 0.000 description 5
- 208000026350 Inborn Genetic disease Diseases 0.000 description 5
- 102100035792 Kininogen-1 Human genes 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 125000002091 cationic group Chemical group 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 238000005538 encapsulation Methods 0.000 description 5
- 208000016361 genetic disease Diseases 0.000 description 5
- 102000045903 human LPA Human genes 0.000 description 5
- 210000005260 human cell Anatomy 0.000 description 5
- 230000002458 infectious effect Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000004806 packaging method and process Methods 0.000 description 5
- 101150066583 rep gene Proteins 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 230000008961 swelling Effects 0.000 description 5
- 230000005030 transcription termination Effects 0.000 description 5
- 241001164823 Adeno-associated virus - 7 Species 0.000 description 4
- 108010028774 Complement C1 Proteins 0.000 description 4
- 102100025406 Complement C1s subcomponent Human genes 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 108010073385 Fibrin Proteins 0.000 description 4
- 102000009123 Fibrin Human genes 0.000 description 4
- 206010019851 Hepatotoxicity Diseases 0.000 description 4
- 101500025164 Homo sapiens Alpha-1-microglobulin Proteins 0.000 description 4
- 101000651439 Homo sapiens Prothrombin Proteins 0.000 description 4
- 229940127379 Kallikrein Inhibitors Drugs 0.000 description 4
- 241000282567 Macaca fascicularis Species 0.000 description 4
- 229930195725 Mannitol Natural products 0.000 description 4
- 241000701945 Parvoviridae Species 0.000 description 4
- 102000035195 Peptidases Human genes 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- 102100027637 Plasma protease C1 inhibitor Human genes 0.000 description 4
- 241000288906 Primates Species 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- 238000011529 RT qPCR Methods 0.000 description 4
- 108020004682 Single-Stranded DNA Proteins 0.000 description 4
- 230000006978 adaptation Effects 0.000 description 4
- 239000003152 bradykinin antagonist Substances 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 230000015271 coagulation Effects 0.000 description 4
- 238000005345 coagulation Methods 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 239000002329 esterase inhibitor Substances 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 229950003499 fibrin Drugs 0.000 description 4
- 230000007686 hepatotoxicity Effects 0.000 description 4
- 229940039715 human prothrombin Drugs 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 239000007951 isotonicity adjuster Substances 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 230000007056 liver toxicity Effects 0.000 description 4
- 239000000594 mannitol Substances 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 238000005457 optimization Methods 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 210000002345 respiratory system Anatomy 0.000 description 4
- 230000001568 sexual effect Effects 0.000 description 4
- 210000000813 small intestine Anatomy 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 230000009261 transgenic effect Effects 0.000 description 4
- 238000003146 transient transfection Methods 0.000 description 4
- 241000649045 Adeno-associated virus 10 Species 0.000 description 3
- 241000649046 Adeno-associated virus 11 Species 0.000 description 3
- 241000649047 Adeno-associated virus 12 Species 0.000 description 3
- 101100524324 Adeno-associated virus 2 (isolate Srivastava/1982) Rep78 gene Proteins 0.000 description 3
- 102100040121 Allograft inflammatory factor 1 Human genes 0.000 description 3
- 241000271566 Aves Species 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- 101800004538 Bradykinin Proteins 0.000 description 3
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 3
- 101000890626 Homo sapiens Allograft inflammatory factor 1 Proteins 0.000 description 3
- 101001040800 Homo sapiens Integral membrane protein GPR180 Proteins 0.000 description 3
- 102100021244 Integral membrane protein GPR180 Human genes 0.000 description 3
- 108060005987 Kallikrein Proteins 0.000 description 3
- 102000001399 Kallikrein Human genes 0.000 description 3
- 241000713666 Lentivirus Species 0.000 description 3
- 108090001030 Lipoproteins Proteins 0.000 description 3
- 102000004895 Lipoproteins Human genes 0.000 description 3
- 108700026244 Open Reading Frames Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 108010076504 Protein Sorting Signals Proteins 0.000 description 3
- 108020004511 Recombinant DNA Proteins 0.000 description 3
- LKAJKIOFIWVMDJ-IYRCEVNGSA-N Stanazolol Chemical compound C([C@@H]1CC[C@H]2[C@@H]3CC[C@@]([C@]3(CC[C@@H]2[C@@]1(C)C1)C)(O)C)C2=C1C=NN2 LKAJKIOFIWVMDJ-IYRCEVNGSA-N 0.000 description 3
- 108091023040 Transcription factor Proteins 0.000 description 3
- 102000040945 Transcription factor Human genes 0.000 description 3
- 108700029229 Transcriptional Regulatory Elements Proteins 0.000 description 3
- 239000000370 acceptor Substances 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 239000001045 blue dye Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 3
- UYRCOTSOPWOSJK-JXTBTVDRSA-N bradykinin antagonist Chemical compound C1C2=CC=CC=C2CC1[C@@H](NC(=O)C(CO)NC(=O)C(NC(=O)CNC(=O)[C@H]1N(C[C@H](O)C1)C(=O)C1N(CCC1)C(=O)C(CCCNC(N)=N)NC(=O)[C@@H](CCCNC(N)=N)NC(=N)CCCCCCC(=N)N[C@H](CCCNC(N)=N)C(=O)NC(CCCNC(N)=N)C(=O)N1C(CCC1)C(=O)N1[C@@H](C[C@@H](O)C1)C(=O)NCC(=O)NC(C1CC2=CC=CC=C2C1)C(=O)NC(CO)C(=O)N[C@H](C1CC2=CC=CC=C2C1)C(=O)N1C2CCCCC2CC1C(=O)NC(CCCNC(N)=N)C(O)=O)C1CC2=CC=CC=C2C1)C(=O)N1C2CCCCC2CC1C(=O)NC(CCCNC(=N)N)C(O)=O UYRCOTSOPWOSJK-JXTBTVDRSA-N 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 239000002131 composite material Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- POZRVZJJTULAOH-LHZXLZLDSA-N danazol Chemical compound C1[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=CC2=C1C=NO2 POZRVZJJTULAOH-LHZXLZLDSA-N 0.000 description 3
- 229960000766 danazol Drugs 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000000412 dendrimer Substances 0.000 description 3
- 229920000736 dendritic polymer Polymers 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 238000004520 electroporation Methods 0.000 description 3
- 229960003699 evans blue Drugs 0.000 description 3
- 238000009396 hybridization Methods 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000001939 inductive effect Effects 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
- 230000000366 juvenile effect Effects 0.000 description 3
- 210000005228 liver tissue Anatomy 0.000 description 3
- 238000010369 molecular cloning Methods 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 230000007170 pathology Effects 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 229920001993 poloxamer 188 Polymers 0.000 description 3
- 229940044519 poloxamer 188 Drugs 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- BBMHARZCALWXSL-UHFFFAOYSA-M sodium dihydrogenphosphate monohydrate Chemical compound O.[Na+].OP(O)([O-])=O BBMHARZCALWXSL-UHFFFAOYSA-M 0.000 description 3
- 229960000912 stanozolol Drugs 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 238000011269 treatment regimen Methods 0.000 description 3
- 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 2
- GCKMFJBGXUYNAG-UHFFFAOYSA-N 17alpha-methyltestosterone Natural products C1CC2=CC(=O)CCC2(C)C2C1C1CCC(C)(O)C1(C)CC2 GCKMFJBGXUYNAG-UHFFFAOYSA-N 0.000 description 2
- 241000300529 Adeno-associated virus 13 Species 0.000 description 2
- 101100524317 Adeno-associated virus 2 (isolate Srivastava/1982) Rep40 gene Proteins 0.000 description 2
- 101100524319 Adeno-associated virus 2 (isolate Srivastava/1982) Rep52 gene Proteins 0.000 description 2
- 101100524321 Adeno-associated virus 2 (isolate Srivastava/1982) Rep68 gene Proteins 0.000 description 2
- 108010003415 Aspartate Aminotransferases Proteins 0.000 description 2
- 102000004625 Aspartate Aminotransferases Human genes 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 108010087504 Beta-Globulins Proteins 0.000 description 2
- 102000006734 Beta-Globulins Human genes 0.000 description 2
- 241000255789 Bombyx mori Species 0.000 description 2
- 241000409811 Bombyx mori nucleopolyhedrovirus Species 0.000 description 2
- 241000282836 Camelus dromedarius Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 241000938605 Crocodylia Species 0.000 description 2
- 239000003154 D dimer Substances 0.000 description 2
- 230000004543 DNA replication Effects 0.000 description 2
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 2
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- 108010080865 Factor XII Proteins 0.000 description 2
- 108010049003 Fibrinogen Proteins 0.000 description 2
- 102000008946 Fibrinogen Human genes 0.000 description 2
- 102100022057 Hepatocyte nuclear factor 1-alpha Human genes 0.000 description 2
- 102100022054 Hepatocyte nuclear factor 4-alpha Human genes 0.000 description 2
- 102100029087 Hepatocyte nuclear factor 6 Human genes 0.000 description 2
- 108010000487 High-Molecular-Weight Kininogen Proteins 0.000 description 2
- 101000771674 Homo sapiens Apolipoprotein E Proteins 0.000 description 2
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 2
- 101001045751 Homo sapiens Hepatocyte nuclear factor 1-alpha Proteins 0.000 description 2
- 101001045740 Homo sapiens Hepatocyte nuclear factor 4-alpha Proteins 0.000 description 2
- 101000988619 Homo sapiens Hepatocyte nuclear factor 6 Proteins 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- GCKMFJBGXUYNAG-HLXURNFRSA-N Methyltestosterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 GCKMFJBGXUYNAG-HLXURNFRSA-N 0.000 description 2
- 101000930477 Mus musculus Albumin Proteins 0.000 description 2
- 101000836282 Mus musculus Solute carrier organic anion transporter family member 1C1 Proteins 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 108091061960 Naked DNA Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- QSLJIVKCVHQPLV-PEMPUTJUSA-N Oxandrin Chemical compound C([C@@H]1CC2)C(=O)OC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@](C)(O)[C@@]2(C)CC1 QSLJIVKCVHQPLV-PEMPUTJUSA-N 0.000 description 2
- 241000121250 Parvovirinae Species 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 241000286209 Phasianidae Species 0.000 description 2
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 description 2
- 229920000954 Polyglycolide Polymers 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
- 108020005067 RNA Splice Sites Proteins 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 2
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 108020004440 Thymidine kinase Proteins 0.000 description 2
- 101150110932 US19 gene Proteins 0.000 description 2
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000001261 affinity purification Methods 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 239000003098 androgen Substances 0.000 description 2
- 229940030486 androgens Drugs 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000000504 antifibrinolytic agent Substances 0.000 description 2
- 108010072035 antithrombin III-protease complex Proteins 0.000 description 2
- 238000013320 baculovirus expression vector system Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 239000004067 bulking agent Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000012761 co-transfection Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 230000024203 complement activation Effects 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 210000001163 endosome Anatomy 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 108010052295 fibrin fragment D Proteins 0.000 description 2
- 229940012952 fibrinogen Drugs 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 102000053020 human ApoE Human genes 0.000 description 2
- 102000057593 human F8 Human genes 0.000 description 2
- 102000044507 human SERPING1 Human genes 0.000 description 2
- 229960000900 human factor viii Drugs 0.000 description 2
- 230000004727 humoral immunity Effects 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 229960001566 methyltestosterone Drugs 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 239000002736 nonionic surfactant Substances 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229960000464 oxandrolone Drugs 0.000 description 2
- ICMWWNHDUZJFDW-DHODBPELSA-N oxymetholone Chemical compound C([C@@H]1CC2)C(=O)\C(=C/O)C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@](C)(O)[C@@]2(C)CC1 ICMWWNHDUZJFDW-DHODBPELSA-N 0.000 description 2
- 229960005244 oxymetholone Drugs 0.000 description 2
- ICMWWNHDUZJFDW-UHFFFAOYSA-N oxymetholone Natural products C1CC2CC(=O)C(=CO)CC2(C)C2C1C1CCC(C)(O)C1(C)CC2 ICMWWNHDUZJFDW-UHFFFAOYSA-N 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 230000008884 pinocytosis Effects 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 239000004633 polyglycolic acid Substances 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 239000007790 solid phase Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- WZDGZWOAQTVYBX-XOINTXKNSA-N tibolone Chemical compound C([C@@H]12)C[C@]3(C)[C@@](C#C)(O)CC[C@H]3[C@@H]1[C@H](C)CC1=C2CCC(=O)C1 WZDGZWOAQTVYBX-XOINTXKNSA-N 0.000 description 2
- 229960001023 tibolone Drugs 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000005026 transcription initiation Effects 0.000 description 2
- 230000002463 transducing effect Effects 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 241001529453 unidentified herpesvirus Species 0.000 description 2
- 241001430294 unidentified retrovirus Species 0.000 description 2
- 230000002227 vasoactive effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 241000958487 Adeno-associated virus 3B Species 0.000 description 1
- 241000701242 Adenoviridae Species 0.000 description 1
- 241000256173 Aedes albopictus Species 0.000 description 1
- 102100022712 Alpha-1-antitrypsin Human genes 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000272525 Anas platyrhynchos Species 0.000 description 1
- 208000028185 Angioedema Diseases 0.000 description 1
- 241000272814 Anser sp. Species 0.000 description 1
- 241000238421 Arthropoda Species 0.000 description 1
- 241000490515 Ascalapha odorata Species 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 241001203868 Autographa californica Species 0.000 description 1
- 241000201370 Autographa californica nucleopolyhedrovirus Species 0.000 description 1
- 101710085045 B2 bradykinin receptor Proteins 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- 208000028399 Critical Illness Diseases 0.000 description 1
- 241000238424 Crustacea Species 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- 101100193633 Danio rerio rag2 gene Proteins 0.000 description 1
- 241000121256 Densovirinae Species 0.000 description 1
- 241000255925 Diptera Species 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 206010072268 Drug-induced liver injury Diseases 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 102000000429 Factor XII Human genes 0.000 description 1
- 108010071241 Factor XIIa Proteins 0.000 description 1
- 108010080805 Factor XIa Proteins 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 101710097382 Fibrinolytic protease Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000700586 Herpesviridae Species 0.000 description 1
- 108091027305 Heteroduplex Proteins 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 101000934958 Homo sapiens Complement C1s subcomponent Proteins 0.000 description 1
- 101000926530 Homo sapiens Eukaryotic translation initiation factor 2-alpha kinase 1 Proteins 0.000 description 1
- 101500025163 Homo sapiens Inter-alpha-trypsin inhibitor light chain Proteins 0.000 description 1
- 101000975003 Homo sapiens Kallistatin Proteins 0.000 description 1
- 101001077723 Homo sapiens Serine protease inhibitor Kazal-type 6 Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 229940122920 Kallikrein inhibitor Drugs 0.000 description 1
- 102100023012 Kallistatin Human genes 0.000 description 1
- 108010093008 Kinins Proteins 0.000 description 1
- 102000002397 Kinins Human genes 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 241000255777 Lepidoptera Species 0.000 description 1
- 108091027974 Mature messenger RNA Proteins 0.000 description 1
- 101100193635 Mus musculus Rag2 gene Proteins 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010030111 Oedema mucosal Diseases 0.000 description 1
- 238000002944 PCR assay Methods 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920001100 Polydextrose Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 102100032859 Protein AMBP Human genes 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 239000012327 Ruthenium complex Substances 0.000 description 1
- 108091006725 SLCO1C1 Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 229940122055 Serine protease inhibitor Drugs 0.000 description 1
- 101710102218 Serine protease inhibitor Proteins 0.000 description 1
- 206010053262 Skin swelling Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 102100027229 Solute carrier organic anion transporter family member 1C1 Human genes 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 108010048889 Thyroxine-Binding Proteins Proteins 0.000 description 1
- 102000009488 Thyroxine-Binding Proteins Human genes 0.000 description 1
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 1
- 102100033117 Toll-like receptor 9 Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 241000255993 Trichoplusia ni Species 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 241000282840 Vicugna vicugna Species 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 108700010877 adenoviridae proteins Proteins 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- ZOJBYZNEUISWFT-UHFFFAOYSA-N allyl isothiocyanate Chemical compound C=CCN=C=S ZOJBYZNEUISWFT-UHFFFAOYSA-N 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- BTBJBAZGXNKLQC-UHFFFAOYSA-N ammonium lauryl sulfate Chemical compound [NH4+].CCCCCCCCCCCCOS([O-])(=O)=O BTBJBAZGXNKLQC-UHFFFAOYSA-N 0.000 description 1
- 229940063953 ammonium lauryl sulfate Drugs 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000002946 anti-pancreatic effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 229920006317 cationic polymer Polymers 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000005101 cell tropism Effects 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000007665 chronic toxicity Effects 0.000 description 1
- 231100000160 chronic toxicity Toxicity 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000010835 comparative analysis Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 210000004443 dendritic cell Anatomy 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 108010011867 ecallantide Proteins 0.000 description 1
- 229960001174 ecallantide Drugs 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 108010073651 fibrinmonomer Proteins 0.000 description 1
- 229960002011 fludrocortisone Drugs 0.000 description 1
- AAXVEMMRQDVLJB-BULBTXNYSA-N fludrocortisone Chemical compound O=C1CC[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 AAXVEMMRQDVLJB-BULBTXNYSA-N 0.000 description 1
- 238000005558 fluorometry Methods 0.000 description 1
- 239000004023 fresh frozen plasma Substances 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 208000034667 hereditary 4 angioedema Diseases 0.000 description 1
- 208000031716 hereditary 5 angioedema Diseases 0.000 description 1
- 208000037232 hereditary 6 angioedema Diseases 0.000 description 1
- 208000034668 hereditary 7 angioedema Diseases 0.000 description 1
- 208000031723 hereditary 8 angioedema Diseases 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- QURWXBZNHXJZBE-SKXRKSCCSA-N icatibant Chemical compound NC(N)=NCCC[C@@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2SC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@H](CC3=CC=CC=C3C2)C(=O)N2[C@@H](C[C@@H]3CCCC[C@@H]32)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O)C[C@@H](O)C1 QURWXBZNHXJZBE-SKXRKSCCSA-N 0.000 description 1
- 108700023918 icatibant Proteins 0.000 description 1
- 229960001062 icatibant Drugs 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 208000015978 inherited metabolic disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000002563 ionic surfactant Substances 0.000 description 1
- VBGWSQKGUZHFPS-VGMMZINCSA-N kalbitor Chemical compound C([C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]2C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=3C=CC=CC=3)C(=O)N[C@H](C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)NCC(=O)NCC(=O)N[C@H]3CSSC[C@H](NC(=O)[C@@H]4CCCN4C(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CO)NC(=O)[C@H](CC=4NC=NC=4)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(O)=O)CSSC[C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC3=O)CSSC2)C(=O)N[C@@H]([C@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=2NC=NC=2)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N1)[C@@H](C)CC)[C@H](C)O)=O)[C@@H](C)CC)C1=CC=CC=C1 VBGWSQKGUZHFPS-VGMMZINCSA-N 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000002479 lipoplex Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000009630 liquid culture Methods 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 208000018191 liver inflammation Diseases 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000008164 mustard oil Substances 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229940012957 plasmin Drugs 0.000 description 1
- 229920001992 poloxamer 407 Polymers 0.000 description 1
- 229940044476 poloxamer 407 Drugs 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000001259 polydextrose Substances 0.000 description 1
- 235000013856 polydextrose Nutrition 0.000 description 1
- 229940035035 polydextrose Drugs 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 230000000379 polymerizing effect Effects 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000004952 protein activity Effects 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000009256 replacement therapy Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 210000004999 sex organ Anatomy 0.000 description 1
- 238000002741 site-directed mutagenesis Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 201000005665 thrombophilia Diseases 0.000 description 1
- 230000005100 tissue tropism Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000007056 transamidation reaction Methods 0.000 description 1
- 102000014898 transaminase activity proteins Human genes 0.000 description 1
- 238000003151 transfection method Methods 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 241000701366 unidentified nuclear polyhedrosis viruses Species 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 210000002845 virion Anatomy 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/005—Enzyme inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61K48/005—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
- 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
- A61K48/0066—Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/81—Protease inhibitors
- C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
- C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
- C07K14/8121—Serpins
-
- 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
- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/14011—Baculoviridae
- C12N2710/14111—Nucleopolyhedrovirus, e.g. autographa californica nucleopolyhedrovirus
- C12N2710/14141—Use of virus, viral particle or viral elements as a vector
- C12N2710/14144—Chimeric viral vector comprising heterologous viral elements for production of another viral 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
- 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
- C12N2750/14122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- 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
- 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
- C12N2830/42—Vector systems having a special element relevant for transcription being an intron or intervening sequence for splicing and/or stability of RNA
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- General Engineering & Computer Science (AREA)
- Biophysics (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- Gastroenterology & Hepatology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Plant Pathology (AREA)
- Microbiology (AREA)
- Diabetes (AREA)
- Immunology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962935359P | 2019-11-14 | 2019-11-14 | |
| US62/935,359 | 2019-11-14 | ||
| US202063016365P | 2020-04-28 | 2020-04-28 | |
| US63/016,365 | 2020-04-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW202128733A true TW202128733A (zh) | 2021-08-01 |
Family
ID=73834586
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW109139830A TW202128733A (zh) | 2019-11-14 | 2020-11-13 | 使用肝特異性基因療法載體之遺傳性血管性水腫的治療 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US20230340078A1 (https=) |
| EP (1) | EP4058475A1 (https=) |
| JP (1) | JP2023503850A (https=) |
| KR (1) | KR20220098210A (https=) |
| CN (1) | CN114829391A (https=) |
| AU (1) | AU2020384294A1 (https=) |
| BR (1) | BR112022009279A2 (https=) |
| CA (1) | CA3161154A1 (https=) |
| CL (1) | CL2022001260A1 (https=) |
| CO (1) | CO2022005641A2 (https=) |
| IL (1) | IL292717A (https=) |
| MX (1) | MX2022005869A (https=) |
| TW (1) | TW202128733A (https=) |
| WO (1) | WO2021097157A1 (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20230407328A1 (en) | 2020-11-02 | 2023-12-21 | Biomarin Pharmaceutical Inc. | Process for enriching adeno-associated virus |
| CA3207268A1 (en) * | 2021-01-27 | 2022-08-04 | Spark Therapeutics, Inc. | Compositions and methods for treating hereditary angioedema |
| KR20240054958A (ko) * | 2021-06-17 | 2024-04-26 | 메이라지티엑스 유케이 Ii 리미티드 | Aav 제조 방법 |
| US20240408240A1 (en) | 2021-10-01 | 2024-12-12 | Biomarin Pharmaceutical Inc. | Treatment of hereditary angioedema with aav gene therapy vectors and therapeutic formulations |
| CN117947040A (zh) | 2022-10-31 | 2024-04-30 | 苏州荷光科汇生物科技有限公司 | 用于目的基因的表达盒及其应用 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4745051A (en) | 1983-05-27 | 1988-05-17 | The Texas A&M University System | Method for producing a recombinant baculovirus expression vector |
| EP0127839B1 (en) | 1983-05-27 | 1992-07-15 | THE TEXAS A&M UNIVERSITY SYSTEM | Method for producing a recombinant baculovirus expression vector |
| ZA848495B (en) | 1984-01-31 | 1985-09-25 | Idaho Res Found | Production of polypeptides in insect cells |
| US6204059B1 (en) | 1994-06-30 | 2001-03-20 | University Of Pittsburgh | AAV capsid vehicles for molecular transfer |
| JPWO2003033710A1 (ja) | 2001-10-16 | 2005-02-03 | 独立行政法人産業技術総合研究所 | 新規ｎ−アセチルグルコサミン転移酵素、それをコードする核酸及びそれに対する抗体並びにこれらの癌若しくは腫瘍診断用途 |
| US6723551B2 (en) | 2001-11-09 | 2004-04-20 | The United States Of America As Represented By The Department Of Health And Human Services | Production of adeno-associated virus in insect cells |
| MX359371B (es) | 2001-11-13 | 2018-09-25 | Univ Pennsylvania | Un metodo para detectar y/o identificar secuencias del virus adeno-asociado y aislamiento de secuencias novedosas identificadas de ese modo. |
| AU2003212708A1 (en) | 2002-03-05 | 2003-09-16 | Stichting Voor De Technische Wetenschappen | Baculovirus expression system |
| AU2003221733A1 (en) * | 2002-04-17 | 2003-11-03 | University Of Florida Research Foundation, Inc. | Improved raav vectors |
| US7943379B2 (en) | 2008-04-30 | 2011-05-17 | Nationwide Children's Hospital, Inc. | Production of rAAV in vero cells using particular adenovirus helpers |
| MX367100B (es) | 2012-02-17 | 2019-08-05 | The Children´S Hospital Of Philadelphia | Composiciones del vector aav y metodos para su transferencia genetica a celulas, organos y tejidos. |
| IL297919A (en) * | 2013-07-22 | 2023-01-01 | Childrens Hospital Philadelphia | Variant aav and compositions, methods and uses for gene transfer to cells, organs and tissues |
| EP3044231B1 (en) * | 2013-09-12 | 2020-08-05 | BioMarin Pharmaceutical Inc. | Aav vectors comprising a gene encoding factor viii |
| US10214731B2 (en) * | 2015-05-28 | 2019-02-26 | Cornell University | Adeno-associated virus mediated delivery of C1E1 as a therapy for angioedema |
| IL305149A (en) | 2016-07-26 | 2023-10-01 | Biomarin Pharm Inc | Novel adeno-associated virus capsid proteins |
| AU2019209770B2 (en) * | 2018-01-16 | 2025-07-31 | Cls Therapeutics Limited | Treatment of diseases by liver expression of an enzyme which has a deoxyribonuclease (DNase) activity |
| CN113164560A (zh) * | 2018-10-26 | 2021-07-23 | Vrije布鲁塞尔大学 | 改善基因疗法的新工具及其用途 |
| WO2021081280A1 (en) * | 2019-10-23 | 2021-04-29 | Shire Human Genetic Therapies, Inc. | Adeno-associated virus vectors based gene therapy for hereditary angioedema |
-
2020
- 2020-11-13 JP JP2022527987A patent/JP2023503850A/ja active Pending
- 2020-11-13 AU AU2020384294A patent/AU2020384294A1/en not_active Abandoned
- 2020-11-13 US US17/777,690 patent/US20230340078A1/en not_active Abandoned
- 2020-11-13 TW TW109139830A patent/TW202128733A/zh unknown
- 2020-11-13 CA CA3161154A patent/CA3161154A1/en active Pending
- 2020-11-13 CN CN202080087888.0A patent/CN114829391A/zh active Pending
- 2020-11-13 KR KR1020227019436A patent/KR20220098210A/ko active Pending
- 2020-11-13 WO PCT/US2020/060337 patent/WO2021097157A1/en not_active Ceased
- 2020-11-13 EP EP20824369.1A patent/EP4058475A1/en not_active Withdrawn
- 2020-11-13 BR BR112022009279A patent/BR112022009279A2/pt not_active IP Right Cessation
- 2020-11-13 MX MX2022005869A patent/MX2022005869A/es unknown
-
2022
- 2022-04-29 CO CONC2022/0005641A patent/CO2022005641A2/es unknown
- 2022-05-03 IL IL292717A patent/IL292717A/en unknown
- 2022-05-13 CL CL2022001260A patent/CL2022001260A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BR112022009279A2 (pt) | 2022-09-06 |
| CN114829391A (zh) | 2022-07-29 |
| CL2022001260A1 (es) | 2023-03-10 |
| US20230340078A1 (en) | 2023-10-26 |
| JP2023503850A (ja) | 2023-02-01 |
| AU2020384294A1 (en) | 2022-06-02 |
| IL292717A (en) | 2022-07-01 |
| WO2021097157A1 (en) | 2021-05-20 |
| KR20220098210A (ko) | 2022-07-11 |
| EP4058475A1 (en) | 2022-09-21 |
| MX2022005869A (es) | 2022-06-14 |
| CO2022005641A2 (es) | 2022-05-20 |
| CA3161154A1 (en) | 2021-05-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20240285806A1 (en) | Stable expression of aav vectors in juvenile subjects | |
| US20240058423A1 (en) | Adeno-Associated Virus Factor VIII Vectors, Associated Viral Particles and Therapeutic Formulations Comprising the Same | |
| US11739345B2 (en) | Methods of treating phenylketonuria | |
| TW202128733A (zh) | 使用肝特異性基因療法載體之遺傳性血管性水腫的治療 | |
| WO2021183895A1 (en) | Treatment of fabry disease with aav gene therapy vectors | |
| WO2021202943A1 (en) | Treatment of phenylketonuria with aav and therapeutic formulations | |
| US20240408240A1 (en) | Treatment of hereditary angioedema with aav gene therapy vectors and therapeutic formulations | |
| US20260091139A1 (en) | Treatment of cardiomyopathy with aav gene therapy vectors | |
| WO2025214477A1 (en) | Treatment of genetic cardiomyopathies with aav gene therapy vectors | |
| TW202421788A (zh) | 用ａａｖ基因療法載體治療致心律不整性心肌病 |