JP2000503534A - アデノウイルスベクターのリコンビナーゼ媒介生成 - Google Patents
アデノウイルスベクターのリコンビナーゼ媒介生成Info
- Publication number
- JP2000503534A JP2000503534A JP9525405A JP52540597A JP2000503534A JP 2000503534 A JP2000503534 A JP 2000503534A JP 9525405 A JP9525405 A JP 9525405A JP 52540597 A JP52540597 A JP 52540597A JP 2000503534 A JP2000503534 A JP 2000503534A
- Authority
- JP
- Japan
- Prior art keywords
- adenovirus
- polynucleotide
- itr
- vector
- dna
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 241000701161 unidentified adenovirus Species 0.000 title claims abstract description 315
- 239000013598 vector Substances 0.000 title claims abstract description 311
- 108010091086 Recombinases Proteins 0.000 title claims description 67
- 102000018120 Recombinases Human genes 0.000 title claims description 67
- 230000001404 mediated effect Effects 0.000 title description 10
- 108091033319 polynucleotide Proteins 0.000 claims abstract description 266
- 102000040430 polynucleotide Human genes 0.000 claims abstract description 266
- 239000002157 polynucleotide Substances 0.000 claims abstract description 265
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 148
- 239000013612 plasmid Substances 0.000 claims abstract description 146
- 230000001177 retroviral effect Effects 0.000 claims abstract description 64
- 238000000034 method Methods 0.000 claims abstract description 54
- 101710192606 Latent membrane protein 2 Proteins 0.000 claims abstract description 37
- 101710109576 Terminal protein Proteins 0.000 claims abstract description 37
- 238000004519 manufacturing process Methods 0.000 claims abstract description 22
- 238000012546 transfer Methods 0.000 claims abstract description 18
- 102100021244 Integral membrane protein GPR180 Human genes 0.000 claims description 179
- 108020004414 DNA Proteins 0.000 claims description 127
- 238000004806 packaging method and process Methods 0.000 claims description 111
- 102000004169 proteins and genes Human genes 0.000 claims description 92
- 241000700605 Viruses Species 0.000 claims description 69
- 241001430294 unidentified retrovirus Species 0.000 claims description 62
- 241001135569 Human adenovirus 5 Species 0.000 claims description 58
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 56
- 230000010076 replication Effects 0.000 claims description 40
- 241000193096 Human adenovirus B3 Species 0.000 claims description 32
- 238000001890 transfection Methods 0.000 claims description 28
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 21
- 230000006798 recombination Effects 0.000 claims description 21
- 238000005215 recombination Methods 0.000 claims description 21
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 229920001184 polypeptide Polymers 0.000 claims description 17
- 108010051219 Cre recombinase Proteins 0.000 claims description 15
- 102100034353 Integrase Human genes 0.000 claims description 13
- 108091034117 Oligonucleotide Proteins 0.000 claims description 13
- 108010052160 Site-specific recombinase Proteins 0.000 claims description 13
- 108010078428 env Gene Products Proteins 0.000 claims description 13
- 108010089520 pol Gene Products Proteins 0.000 claims description 13
- 102000004190 Enzymes Human genes 0.000 claims description 12
- 108090000790 Enzymes Proteins 0.000 claims description 12
- 239000002773 nucleotide Substances 0.000 claims description 10
- 125000003729 nucleotide group Chemical group 0.000 claims description 10
- 101710177291 Gag polyprotein Proteins 0.000 claims description 9
- 101710125418 Major capsid protein Proteins 0.000 claims description 7
- 239000003550 marker Substances 0.000 claims description 7
- 108010024878 Adenovirus E1A Proteins Proteins 0.000 claims description 3
- 108010087905 Adenovirus E1B Proteins Proteins 0.000 claims description 3
- 108700015342 adenovirus terminal Proteins 0.000 claims description 3
- 230000035772 mutation Effects 0.000 claims description 3
- 241000894007 species Species 0.000 claims description 3
- 230000002431 foraging effect Effects 0.000 claims description 2
- 230000002463 transducing effect Effects 0.000 claims description 2
- 230000005540 biological transmission Effects 0.000 claims 4
- 101150087426 Gnal gene Proteins 0.000 claims 3
- 101710193739 Protein RecA Proteins 0.000 claims 1
- 108010067390 Viral Proteins Proteins 0.000 claims 1
- 108700010832 inovirus proteins Proteins 0.000 claims 1
- 238000010397 one-hybrid screening Methods 0.000 claims 1
- 238000001727 in vivo Methods 0.000 abstract description 7
- 238000012239 gene modification Methods 0.000 abstract description 3
- 230000005017 genetic modification Effects 0.000 abstract description 3
- 235000013617 genetically modified food Nutrition 0.000 abstract description 3
- 238000012216 screening Methods 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 172
- 239000012634 fragment Substances 0.000 description 32
- 108010005774 beta-Galactosidase Proteins 0.000 description 20
- 108010054218 Factor VIII Proteins 0.000 description 19
- 102000001690 Factor VIII Human genes 0.000 description 19
- 229960000301 factor viii Drugs 0.000 description 19
- 239000002245 particle Substances 0.000 description 19
- 102000005936 beta-Galactosidase Human genes 0.000 description 18
- 239000003814 drug Substances 0.000 description 16
- 238000010361 transduction Methods 0.000 description 16
- 210000003494 hepatocyte Anatomy 0.000 description 15
- 238000003752 polymerase chain reaction Methods 0.000 description 15
- 210000001519 tissue Anatomy 0.000 description 15
- 230000026683 transduction Effects 0.000 description 15
- 238000011144 upstream manufacturing Methods 0.000 description 14
- 239000006166 lysate Substances 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- 238000010276 construction Methods 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 208000015181 infectious disease Diseases 0.000 description 11
- 229940124597 therapeutic agent Drugs 0.000 description 11
- 108700019146 Transgenes Proteins 0.000 description 10
- AIYUHDOJVYHVIT-UHFFFAOYSA-M caesium chloride Chemical compound [Cl-].[Cs+] AIYUHDOJVYHVIT-UHFFFAOYSA-M 0.000 description 10
- 229940088598 enzyme Drugs 0.000 description 9
- 210000000056 organ Anatomy 0.000 description 9
- 210000003527 eukaryotic cell Anatomy 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 230000008488 polyadenylation Effects 0.000 description 8
- 239000013603 viral vector Substances 0.000 description 8
- 108010088751 Albumins Proteins 0.000 description 7
- 102000009027 Albumins Human genes 0.000 description 7
- 238000012217 deletion Methods 0.000 description 7
- 230000037430 deletion Effects 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 230000002458 infectious effect Effects 0.000 description 7
- 239000009235 prelox Substances 0.000 description 7
- 230000003612 virological effect Effects 0.000 description 7
- OPIFSICVWOWJMJ-AEOCFKNESA-N 5-bromo-4-chloro-3-indolyl beta-D-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1OC1=CNC2=CC=C(Br)C(Cl)=C12 OPIFSICVWOWJMJ-AEOCFKNESA-N 0.000 description 6
- 108091026890 Coding region Proteins 0.000 description 6
- 241000713869 Moloney murine leukemia virus Species 0.000 description 6
- 238000002105 Southern blotting Methods 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 230000000692 anti-sense effect Effects 0.000 description 6
- 230000032823 cell division Effects 0.000 description 6
- 230000000120 cytopathologic effect Effects 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 230000002068 genetic effect Effects 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 230000001939 inductive effect Effects 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 210000000234 capsid Anatomy 0.000 description 5
- 210000004671 cell-free system Anatomy 0.000 description 5
- 230000007812 deficiency Effects 0.000 description 5
- 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 5
- 229960003957 dexamethasone Drugs 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 230000006801 homologous recombination Effects 0.000 description 5
- 238000002744 homologous recombination Methods 0.000 description 5
- 230000006698 induction Effects 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 241000701022 Cytomegalovirus Species 0.000 description 4
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 4
- 101100379247 Salmo trutta apoa1 gene Proteins 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 238000010586 diagram Methods 0.000 description 4
- 239000003623 enhancer Substances 0.000 description 4
- 238000003780 insertion Methods 0.000 description 4
- 230000037431 insertion Effects 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- 102100022641 Coagulation factor IX Human genes 0.000 description 3
- 241000701959 Escherichia virus Lambda Species 0.000 description 3
- 102000003972 Fibroblast growth factor 7 Human genes 0.000 description 3
- 208000009292 Hemophilia A Diseases 0.000 description 3
- 102000015696 Interleukins Human genes 0.000 description 3
- 108010063738 Interleukins Proteins 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 102000019197 Superoxide Dismutase Human genes 0.000 description 3
- 108010012715 Superoxide dismutase Proteins 0.000 description 3
- 108020004440 Thymidine kinase Proteins 0.000 description 3
- 241000711517 Torovirus Species 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 108010006025 bovine growth hormone Proteins 0.000 description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- 238000005119 centrifugation Methods 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 230000029087 digestion Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 3
- 208000006454 hepatitis Diseases 0.000 description 3
- 231100000283 hepatitis Toxicity 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 102000057593 human F8 Human genes 0.000 description 3
- 229960000900 human factor viii Drugs 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000010354 integration Effects 0.000 description 3
- 229940047122 interleukins Drugs 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 230000029812 viral genome replication Effects 0.000 description 3
- 102100022712 Alpha-1-antitrypsin Human genes 0.000 description 2
- 241000701106 Bovine adenovirus 3 Species 0.000 description 2
- 101100028791 Caenorhabditis elegans pbs-5 gene Proteins 0.000 description 2
- 102100026735 Coagulation factor VIII Human genes 0.000 description 2
- 206010010144 Completed suicide Diseases 0.000 description 2
- 201000003883 Cystic fibrosis Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108010076282 Factor IX Proteins 0.000 description 2
- 201000003542 Factor VIII deficiency Diseases 0.000 description 2
- 241001135572 Human adenovirus E4 Species 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- 108010001831 LDL receptors Proteins 0.000 description 2
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 2
- 208000019693 Lung disease Diseases 0.000 description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 102100028200 Ornithine transcarbamylase, mitochondrial Human genes 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 102000006601 Thymidine Kinase Human genes 0.000 description 2
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 2
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 210000002798 bone marrow cell Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 239000013611 chromosomal DNA Substances 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 108700004025 env Genes Proteins 0.000 description 2
- 229960004222 factor ix Drugs 0.000 description 2
- 238000001415 gene therapy Methods 0.000 description 2
- 208000002672 hepatitis B Diseases 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 210000005265 lung cell Anatomy 0.000 description 2
- 239000003580 lung surfactant Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 230000036457 multidrug resistance Effects 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 230000021625 positive regulation of cell division Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 description 2
- 210000000605 viral structure Anatomy 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-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
- WDGXQSVUSMTYNG-UHFFFAOYSA-N 2-Methyl-3-(2-methylphenyl)-3,4-dihydroquinazolin-4-one [2-(diphenylmethoxy)ethyl]dimethylamine hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1.CC1=CC=CC=C1N1C(=O)C2=CC=CC=C2N=C1C WDGXQSVUSMTYNG-UHFFFAOYSA-N 0.000 description 1
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
- CONKBQPVFMXDOV-QHCPKHFHSA-N 6-[(5S)-5-[[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]methyl]-2-oxo-1,3-oxazolidin-3-yl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C[C@H]1CN(C(O1)=O)C1=CC2=C(NC(O2)=O)C=C1 CONKBQPVFMXDOV-QHCPKHFHSA-N 0.000 description 1
- 102100036664 Adenosine deaminase Human genes 0.000 description 1
- 102000055025 Adenosine deaminases Human genes 0.000 description 1
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 241000710929 Alphavirus Species 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 102000008076 Angiogenic Proteins Human genes 0.000 description 1
- 108010074415 Angiogenic Proteins Proteins 0.000 description 1
- 108010027070 Apolipoproteins C Proteins 0.000 description 1
- 108010025628 Apolipoproteins E Proteins 0.000 description 1
- 102000013918 Apolipoproteins E Human genes 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 208000014644 Brain disease Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 101150029409 CFTR gene Proteins 0.000 description 1
- 101100298998 Caenorhabditis elegans pbs-3 gene Proteins 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 102100035882 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 206010010099 Combined immunodeficiency Diseases 0.000 description 1
- 102100025287 Cytochrome b Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010075028 Cytochromes b Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 230000007018 DNA scission Effects 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 108010069091 Dystrophin Proteins 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
- 206010014759 Endometrial neoplasm Diseases 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 1
- 241000702191 Escherichia virus P1 Species 0.000 description 1
- 102000002464 Galactosidases Human genes 0.000 description 1
- 108010093031 Galactosidases Proteins 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 102000004547 Glucosylceramidase Human genes 0.000 description 1
- 108010017544 Glucosylceramidase Proteins 0.000 description 1
- 108010063907 Glutathione Reductase Proteins 0.000 description 1
- 102100036442 Glutathione reductase, mitochondrial 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
- 101150071666 HBA gene Proteins 0.000 description 1
- 108091005902 Hemoglobin subunit alpha Proteins 0.000 description 1
- 108091005904 Hemoglobin subunit beta Proteins 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 206010019786 Hepatitis non-A non-B Diseases 0.000 description 1
- 206010019799 Hepatitis viral Diseases 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 108010007267 Hirudins Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000823116 Homo sapiens Alpha-1-antitrypsin Proteins 0.000 description 1
- 101000986595 Homo sapiens Ornithine transcarbamylase, mitochondrial Proteins 0.000 description 1
- 241000701109 Human adenovirus 2 Species 0.000 description 1
- 108010091358 Hypoxanthine Phosphoribosyltransferase Proteins 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 102000000646 Interleukin-3 Human genes 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 241000726306 Irus Species 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 102000008299 Nitric Oxide Synthase Human genes 0.000 description 1
- 108010021487 Nitric Oxide Synthase Proteins 0.000 description 1
- 241000724832 Non-A, non-B hepatitis virus Species 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 208000000599 Ornithine Carbamoyltransferase Deficiency Disease Diseases 0.000 description 1
- 101710198224 Ornithine carbamoyltransferase, mitochondrial Proteins 0.000 description 1
- 206010052450 Ornithine transcarbamoylase deficiency Diseases 0.000 description 1
- 208000035903 Ornithine transcarbamylase deficiency Diseases 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 238000010222 PCR analysis Methods 0.000 description 1
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 1
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 1
- 201000011252 Phenylketonuria Diseases 0.000 description 1
- 102000052575 Proto-Oncogene Human genes 0.000 description 1
- 108700020978 Proto-Oncogene Proteins 0.000 description 1
- 102000007620 Pulmonary Surfactant-Associated Protein C Human genes 0.000 description 1
- 108010007125 Pulmonary Surfactant-Associated Protein C Proteins 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 108091008874 T cell receptors Proteins 0.000 description 1
- 108010092262 T-Cell Antigen Receptors Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 208000002903 Thalassemia Diseases 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 101900150902 Varicella-zoster virus Thymidine kinase Proteins 0.000 description 1
- 108020005202 Viral DNA Proteins 0.000 description 1
- 108010087302 Viral Structural Proteins Proteins 0.000 description 1
- 108010006886 Vitrogen Proteins 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 201000009628 adenosine deaminase deficiency Diseases 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 229940024142 alpha 1-antitrypsin Drugs 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000003263 anti-adenoviral effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 208000036556 autosomal recessive T cell-negative B cell-negative NK cell-negative due to adenosine deaminase deficiency severe combined immunodeficiency Diseases 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000005980 beta thalassemia Diseases 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 208000022806 beta-thalassemia major Diseases 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- -1 but not limited to Proteins 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 238000012761 co-transfection Methods 0.000 description 1
- 210000002314 coated vesicle Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- TVZPLCNGKSPOJA-UHFFFAOYSA-N copper zinc Chemical compound [Cu].[Zn] TVZPLCNGKSPOJA-UHFFFAOYSA-N 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000005034 decoration Methods 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 238000000432 density-gradient centrifugation Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 210000001842 enterocyte Anatomy 0.000 description 1
- 101150030339 env gene Proteins 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000012869 ethanol precipitation Methods 0.000 description 1
- 238000001400 expression cloning Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 229960002963 ganciclovir Drugs 0.000 description 1
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 208000037824 growth disorder Diseases 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000009429 hemophilia B Diseases 0.000 description 1
- 108010034429 heregulin alpha Proteins 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 229960001388 interferon-beta Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940076264 interleukin-3 Drugs 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000004966 intestinal stem cell Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 238000000464 low-speed centrifugation Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 210000005033 mesothelial cell Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 210000003098 myoblast Anatomy 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000005937 nuclear translocation Effects 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 201000011278 ornithine carbamoyltransferase deficiency Diseases 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 210000004738 parenchymal cell Anatomy 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 108700004029 pol Genes Proteins 0.000 description 1
- 210000003240 portal vein Anatomy 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 108010043277 recombinant soluble CD4 Proteins 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108090000446 ribonuclease T(2) Proteins 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 229940116736 romycin Drugs 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 210000003014 totipotent stem cell Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000002753 trypsin inhibitor Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)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)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(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](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 201000001862 viral hepatitis Diseases 0.000 description 1
- 210000002845 virion Anatomy 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
-
- 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
- C12N2710/10011—Adenoviridae
- C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
- C12N2710/10341—Use of virus, viral particle or viral elements as a vector
- C12N2710/10343—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2800/00—Nucleic acids vectors
- C12N2800/10—Plasmid DNA
- C12N2800/108—Plasmid DNA episomal vectors
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2800/00—Nucleic acids vectors
- C12N2800/30—Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT
-
- 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
- C12N2830/001—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination
- C12N2830/002—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor
-
- 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
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Virology (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Pulse, Heart Rate, Blood Pressure Or Blood Flow (AREA)
- Ultra Sonic Daignosis Equipment (AREA)
- Oscillators With Electromechanical Resonators (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US58370396A | 1996-01-05 | 1996-01-05 | |
| US08/583,703 | 1996-01-05 | ||
| PCT/US1997/000370 WO1997025446A1 (en) | 1996-01-05 | 1997-01-03 | Recombinase-mediated generation of adenoviral vectors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2000503534A true JP2000503534A (ja) | 2000-03-28 |
| JP2000503534A5 JP2000503534A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2004-11-11 |
Family
ID=24334219
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9525405A Ceased JP2000503534A (ja) | 1996-01-05 | 1997-01-03 | アデノウイルスベクターのリコンビナーゼ媒介生成 |
Country Status (7)
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6730507B1 (en) | 1993-06-24 | 2004-05-04 | Merck & Co., Inc. | Use of helper-dependent adenoviral vectors of alternative serotypes permits repeat vector administration |
| US6379943B1 (en) * | 1999-03-05 | 2002-04-30 | Merck & Co., Inc. | High-efficiency Cre/loxp based system for construction of adenovirus vectors |
| US6756226B2 (en) * | 1994-05-31 | 2004-06-29 | Frank L. Graham | Enhanced system for construction of adenovirus vectors |
| US6720140B1 (en) | 1995-06-07 | 2004-04-13 | Invitrogen Corporation | Recombinational cloning using engineered recombination sites |
| US6964861B1 (en) | 1998-11-13 | 2005-11-15 | Invitrogen Corporation | Enhanced in vitro recombinational cloning of using ribosomal proteins |
| US6143557A (en) | 1995-06-07 | 2000-11-07 | Life Technologies, Inc. | Recombination cloning using engineered recombination sites |
| US6974694B2 (en) | 1995-06-07 | 2005-12-13 | Advec, Inc. | Adenoviruses for control of gene expression |
| EP0937098B1 (en) | 1995-06-07 | 2002-08-14 | Invitrogen Corporation | Recombinational cloning in vitro using engineered recombination sites |
| FR2749857B1 (fr) * | 1996-06-12 | 1998-08-14 | Centre Nat Rech Scient | Generation de molecules replicatives in vivo |
| CA2272121A1 (en) * | 1996-11-19 | 1998-05-28 | Uab Research Foundation | Chimeric retrovirus/adenovirus system |
| US6403370B1 (en) * | 1997-02-10 | 2002-06-11 | Genstar Therapeutics Corporation | Oncolytic/immunogenic complementary-adenoviral vector system |
| US7030096B1 (en) * | 1997-02-13 | 2006-04-18 | Albert Einstein College Of Medicine Of Yeshiva University | Method of enhancing relaxation of penile smooth muscle by introduction of DNA encoding maxi-K potassium channel protein |
| US5851808A (en) | 1997-02-28 | 1998-12-22 | Baylor College Of Medicine | Rapid subcloning using site-specific recombination |
| WO1998042856A1 (en) | 1997-03-21 | 1998-10-01 | Enzo Therapeutics, Inc., A Fully Owned Subsidiary Of Enzo Biochem, Inc. | Vectors and viral vectors, and packaging cell lines for propagating same |
| WO1998046778A1 (en) * | 1997-04-11 | 1998-10-22 | The Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services | Transgenomic viruses and the use thereof |
| ATE303448T1 (de) | 1997-09-23 | 2005-09-15 | Genvec Inc | Duale selektionkassette und sie enthaltende plasmide |
| NZ520579A (en) * | 1997-10-24 | 2004-08-27 | Invitrogen Corp | Recombinational cloning using nucleic acids having recombination sites and methods for synthesizing double stranded nucleic acids |
| US7351578B2 (en) | 1999-12-10 | 2008-04-01 | Invitrogen Corp. | Use of multiple recombination sites with unique specificity in recombinational cloning |
| DE19807265C2 (de) * | 1998-02-20 | 2000-01-05 | Centeon Pharma Gmbh | Adenoviraler Transfervektor für den Gentransport einer DNA-Sequenz |
| US6413776B1 (en) * | 1998-06-12 | 2002-07-02 | Galapagos Geonomics N.V. | High throughput screening of gene function using adenoviral libraries for functional genomics applications |
| US6576463B1 (en) | 1999-01-15 | 2003-06-10 | The Regents Of The University Of California | Hybrid vectors for gene therapy |
| CA2363924A1 (en) | 1999-03-02 | 2000-09-08 | Invitrogen Corporation | Compositions and methods for use in recombinational cloning of nucleic acids |
| CA2366914C (en) * | 1999-03-05 | 2010-05-11 | Merck & Co., Inc. | Enhanced system for construction of adenovirus vectors |
| AU785483B2 (en) | 1999-12-10 | 2007-09-20 | Invitrogen Corporation | Use of multiple recombination sites with unique specificity in recombinational cloning |
| US7052904B2 (en) | 2000-01-31 | 2006-05-30 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Hybrid adeno-retroviral vector for the transfection of cells |
| US7244560B2 (en) | 2000-05-21 | 2007-07-17 | Invitrogen Corporation | Methods and compositions for synthesis of nucleic acid molecules using multiple recognition sites |
| US7198924B2 (en) | 2000-12-11 | 2007-04-03 | Invitrogen Corporation | Methods and compositions for synthesis of nucleic acid molecules using multiple recognition sites |
| EP1320620B1 (en) | 2000-09-25 | 2015-01-21 | The Regents Of The University Of Michigan | Production of viral vectors |
| US7723102B2 (en) * | 2000-09-28 | 2010-05-25 | Bayer Corporation | Enhanced transfection system |
| WO2002061104A2 (en) | 2001-01-30 | 2002-08-08 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Hybrid adenoviral vector |
| JP2004532039A (ja) * | 2001-03-26 | 2004-10-21 | ザ ボード オブ トラスティーズ オブ ザ リーランド スタンフォード ジュニア ユニバーシティ | ヘルパー依存性アデノウイルスベクター系およびその系の使用方法 |
| WO2002085287A2 (en) * | 2001-04-18 | 2002-10-31 | Genstar Therapeutics Corp. | Minimal adenoviral vectors for immunization |
| WO2003062400A2 (en) * | 2002-01-24 | 2003-07-31 | The Scripps Research Institute | Fiber shaft modifications for efficient targeting |
| US8304233B2 (en) | 2002-06-04 | 2012-11-06 | Poetic Genetics, Llc | Methods of unidirectional, site-specific integration into a genome, compositions and kits for practicing the same |
| US20040203133A1 (en) * | 2003-01-07 | 2004-10-14 | Anja Ehrhardt | Helper dependent adenoviral vector system and methods for using the same |
| EP1616016B1 (en) * | 2003-03-19 | 2012-11-14 | Isogenis, Inc. | Gene therapy vectors having reduced immunogenicity based on cd8 alpha-chain |
| CA2519680A1 (en) | 2003-03-28 | 2004-11-18 | The Scripps Research Institute | Adenovirus particles with enhanced infectivity of dendritic cells and particles with decreased infectivity of hepatocytes |
| DE602004027538D1 (de) | 2003-12-01 | 2010-07-15 | Life Technologies Corp | Rekombinationsstellen enthaltende nukleinsäuremoleküle und verfahren zur verwendung davon |
| US20090053249A1 (en) * | 2004-07-20 | 2009-02-26 | Yan Qi | Specific Inhibition of Autoimmunity and Diseases Associated With Autoantigens |
| EP1804835B9 (en) | 2004-09-13 | 2010-09-29 | Genzyme Corporation | Multimeric constructs |
| AR059089A1 (es) | 2006-01-20 | 2008-03-12 | Genzyme Corp | Administracion intraventricular de una enzima para enfermedades de almacenamiento lisosomal |
| LT1988823T (lt) | 2006-02-09 | 2018-12-10 | Genzyme Corporation | Lėtas intraventrikuliarinis pateikimas |
| WO2010033722A2 (en) | 2008-09-17 | 2010-03-25 | Isogenis, Inc. | Construction of fully-deleted adenovirus-based gene delivery vectors and uses thereof |
| US20230172175A1 (en) | 2020-03-15 | 2023-06-08 | Proteinea, Inc. | Recombinant protein production in insects |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1293460C (en) * | 1985-10-07 | 1991-12-24 | Brian Lee Sauer | Site-specific recombination of dna in yeast |
| WO1994023582A1 (en) * | 1993-04-08 | 1994-10-27 | Genetic Therapy, Inc. | Adenoviral vectors including dna encoding lung surfactant protein |
| US5919676A (en) * | 1993-06-24 | 1999-07-06 | Advec, Inc. | Adenoviral vector system comprising Cre-loxP recombination |
| US6686200B1 (en) * | 1993-08-31 | 2004-02-03 | Uab Research Foundation | Methods and compositions for the large scale production of recombinant adeno-associated virus |
| CA2192442C (en) * | 1994-06-10 | 2007-09-25 | Imre Kovesdi | Complementary adenoviral vector systems and cell lines |
| US5650309A (en) * | 1995-05-16 | 1997-07-22 | The Regents Of The University Of California | Viral vectors |
-
1997
- 1997-01-03 EP EP97902882A patent/EP0927263A1/en not_active Withdrawn
- 1997-01-03 JP JP9525405A patent/JP2000503534A/ja not_active Ceased
- 1997-01-03 WO PCT/US1997/000370 patent/WO1997025446A1/en not_active Application Discontinuation
- 1997-01-03 CA CA002239366A patent/CA2239366A1/en not_active Abandoned
- 1997-01-03 US US09/051,579 patent/US6156497A/en not_active Expired - Fee Related
- 1997-01-03 NZ NZ330553A patent/NZ330553A/en unknown
- 1997-01-03 AU AU16951/97A patent/AU1695197A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CA2239366A1 (en) | 1997-07-17 |
| NZ330553A (en) | 2001-04-27 |
| AU1695197A (en) | 1997-08-01 |
| EP0927263A4 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1999-07-07 |
| WO1997025446A1 (en) | 1997-07-17 |
| US6156497A (en) | 2000-12-05 |
| EP0927263A1 (en) | 1999-07-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2000503534A (ja) | アデノウイルスベクターのリコンビナーゼ媒介生成 | |
| JP3565859B2 (ja) | 改良されたアデノウイルスおよびその使用法 | |
| WO1997025446A9 (en) | Recombinase-mediated generation of adenoviral vectors | |
| Zhou et al. | Development of a complementing cell line and a system for construction of adenovirus vectors with E1 and E2a deleted | |
| US6228646B1 (en) | Helper-free, totally defective adenovirus for gene therapy | |
| US7195896B2 (en) | Complementary adenoviral vector systems and cell lines | |
| AU709498B2 (en) | Improved adenoviral vectors and producer cells | |
| US6350575B1 (en) | Helper viruses for the preparation of recombinant viral vectors | |
| JPH11502421A (ja) | 相補的なアデノウイルスベクター系と細胞株 | |
| JP2001510998A (ja) | 変更されたヘキソン蛋白質を有するアデノウィルス | |
| JPH10507928A (ja) | ハイブリッドアデノウイルス−ａａｖウイルスおよびその使用方法 | |
| JP2000106875A (ja) | 目的遺伝子の発現を改善するためのアデノウイルスｅ４リ―ディングフレ―ムの使用 | |
| JP2001502883A (ja) | ミニアデノウイルスベクター | |
| JP4386971B2 (ja) | スプライシング配列を含んでなる組換えアデノウイルスベクター | |
| JP2001505047A (ja) | 高キャパシティーアデノウイルスベクターの開発の促進に使用するためのパッケージング細胞系 | |
| WO2000042208A1 (en) | Adenovirus vectors, packaging cell lines, compositions, and methods for preparation and use | |
| US20030192066A1 (en) | Minimal adenoviral vector | |
| JP2003508057A (ja) | 改変アデノウイルスファイバーおよび用途 | |
| US7094398B1 (en) | Recombinant adenoviral vectors expressing chimeric fiber proteins for cell specific infection and genome integration | |
| WO2002008436A2 (en) | Mini-adenoviral vector system for vaccination | |
| US20040208846A1 (en) | Mini-Ad vector for immunization | |
| HU224175B1 (hu) | Vírus vektorok cirkuláris, replikálódó DNS molekulák in situ előállítására | |
| WO2002085287A2 (en) | Minimal adenoviral vectors for immunization | |
| AU3345801A (en) | Recombinase-mediated generation of adenoviral vectors | |
| JPH10512276A (ja) | 遺伝子治療による治療薬の送達 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20031226 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20031226 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20070605 |
|
| A313 | Final decision of rejection without a dissenting response from the applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A313 Effective date: 20071024 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20071225 |