JP2000514641A - 異種移植拒絶を低減するための方法および組成物 - Google Patents
異種移植拒絶を低減するための方法および組成物Info
- Publication number
- JP2000514641A JP2000514641A JP09517615A JP51761597A JP2000514641A JP 2000514641 A JP2000514641 A JP 2000514641A JP 09517615 A JP09517615 A JP 09517615A JP 51761597 A JP51761597 A JP 51761597A JP 2000514641 A JP2000514641 A JP 2000514641A
- Authority
- JP
- Japan
- Prior art keywords
- transgenic
- cells
- human
- nucleic acid
- organs
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 64
- 239000000203 mixture Substances 0.000 title abstract description 5
- 210000004027 cell Anatomy 0.000 claims abstract description 220
- 230000009261 transgenic effect Effects 0.000 claims abstract description 124
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 78
- 150000001720 carbohydrates Chemical class 0.000 claims abstract description 76
- 241001465754 Metazoa Species 0.000 claims abstract description 57
- QIGJYVCQYDKYDW-SDOYDPJRSA-N alpha-D-galactosyl-(1->3)-D-galactose 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](CO)OC(O)[C@@H]1O QIGJYVCQYDKYDW-SDOYDPJRSA-N 0.000 claims abstract description 49
- 210000000056 organ Anatomy 0.000 claims abstract description 49
- 230000014509 gene expression Effects 0.000 claims abstract description 41
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 30
- 102000004190 Enzymes Human genes 0.000 claims abstract description 25
- 108090000790 Enzymes Proteins 0.000 claims abstract description 25
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 15
- 238000002689 xenotransplantation Methods 0.000 claims description 5
- 101710183434 ATPase Proteins 0.000 claims 1
- 101710088369 Bacterial RNA polymerase inhibitor Proteins 0.000 claims 1
- 101710086913 DNA polymerase Proteins 0.000 claims 1
- 230000008520 organization Effects 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 abstract description 41
- 230000004044 response Effects 0.000 abstract description 21
- 210000000987 immune system Anatomy 0.000 abstract description 12
- 108020004707 nucleic acids Proteins 0.000 abstract description 8
- 102000039446 nucleic acids Human genes 0.000 abstract description 8
- 210000005260 human cell Anatomy 0.000 abstract description 4
- 108010049936 agalsidase alfa Proteins 0.000 abstract description 3
- 230000021633 leukocyte mediated immunity Effects 0.000 abstract description 2
- 235000014633 carbohydrates Nutrition 0.000 description 74
- 108010030291 alpha-Galactosidase Proteins 0.000 description 56
- 102000005840 alpha-Galactosidase Human genes 0.000 description 56
- 239000002299 complementary DNA Substances 0.000 description 35
- 210000003743 erythrocyte Anatomy 0.000 description 24
- 239000000047 product Substances 0.000 description 22
- 102000030902 Galactosyltransferase Human genes 0.000 description 21
- 108060003306 Galactosyltransferase Proteins 0.000 description 21
- 108090000992 Transferases Proteins 0.000 description 20
- 102000004357 Transferases Human genes 0.000 description 19
- 108700019146 Transgenes Proteins 0.000 description 17
- 238000010186 staining Methods 0.000 description 15
- 230000009089 cytolysis Effects 0.000 description 14
- 239000000463 material Substances 0.000 description 14
- 230000000295 complement effect Effects 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 210000002966 serum Anatomy 0.000 description 12
- 238000001890 transfection Methods 0.000 description 12
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 11
- 230000001404 mediated effect Effects 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- 230000007423 decrease Effects 0.000 description 10
- 239000002523 lectin Substances 0.000 description 10
- 238000012546 transfer Methods 0.000 description 10
- 108090001090 Lectins Proteins 0.000 description 9
- 102000004856 Lectins Human genes 0.000 description 9
- 238000001727 in vivo Methods 0.000 description 9
- -1 Galα (1,3) Gal carbohydrates Chemical class 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 7
- 101000718525 Homo sapiens Alpha-galactosidase A Proteins 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 102000043404 human GLA Human genes 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 241000588724 Escherichia coli Species 0.000 description 6
- 239000012634 fragment Substances 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 238000010561 standard procedure Methods 0.000 description 6
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 5
- 241000282887 Suidae Species 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 125000002519 galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 description 5
- 230000035931 haemagglutination Effects 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 102000002464 Galactosidases Human genes 0.000 description 4
- 108010093031 Galactosidases Proteins 0.000 description 4
- 101000716130 Homo sapiens CD48 antigen Proteins 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 210000002798 bone marrow cell Anatomy 0.000 description 4
- 210000002889 endothelial cell Anatomy 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 239000006166 lysate Substances 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 238000011830 transgenic mouse model Methods 0.000 description 4
- 238000002054 transplantation Methods 0.000 description 4
- 108091026890 Coding region Proteins 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- 125000003275 alpha amino acid group Chemical group 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 238000012761 co-transfection Methods 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000013598 vector Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- IFBHRQDFSNCLOZ-IIRVCBMXSA-N 4-nitrophenyl-α-d-galactoside Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC1=CC=C([N+]([O-])=O)C=C1 IFBHRQDFSNCLOZ-IIRVCBMXSA-N 0.000 description 2
- 102100036008 CD48 antigen Human genes 0.000 description 2
- 241000283707 Capra Species 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
- 241001669573 Galeorhinus galeus Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229920004890 Triton X-100 Polymers 0.000 description 2
- 239000013504 Triton X-100 Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 239000013592 cell lysate Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000004186 co-expression Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000009402 cross-breeding Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 239000013604 expression vector Substances 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 238000010363 gene targeting Methods 0.000 description 2
- 102000046585 human CD48 Human genes 0.000 description 2
- 230000002998 immunogenetic effect Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 2
- 239000013615 primer Substances 0.000 description 2
- 238000010839 reverse transcription Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 208000010370 Adenoviridae Infections Diseases 0.000 description 1
- 206010060931 Adenovirus infection Diseases 0.000 description 1
- 108700028369 Alleles Proteins 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 238000009010 Bradford assay Methods 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- 102100022002 CD59 glycoprotein Human genes 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 108020004638 Circular DNA Proteins 0.000 description 1
- 101710172562 Cobra venom factor Proteins 0.000 description 1
- 240000007154 Coffea arabica Species 0.000 description 1
- 102100025680 Complement decay-accelerating factor Human genes 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 108010008286 DNA nucleotidylexotransferase Proteins 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 102100029764 DNA-directed DNA/RNA polymerase mu Human genes 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101000798869 Escherichia phage Mu DDE-recombinase A Proteins 0.000 description 1
- 241000219726 Griffonia simplicifolia Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000897400 Homo sapiens CD59 glycoprotein Proteins 0.000 description 1
- 101000856022 Homo sapiens Complement decay-accelerating factor Proteins 0.000 description 1
- 101000961414 Homo sapiens Membrane cofactor protein Proteins 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
- 241000406668 Loxodonta cyclotis Species 0.000 description 1
- 102100039373 Membrane cofactor protein Human genes 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 102000005348 Neuraminidase Human genes 0.000 description 1
- 108010006232 Neuraminidase Proteins 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 241000282376 Panthera tigris Species 0.000 description 1
- 241000282520 Papio Species 0.000 description 1
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- 208000005074 Retroviridae Infections Diseases 0.000 description 1
- 101000718529 Saccharolobus solfataricus (strain ATCC 35092 / DSM 1617 / JCM 11322 / P2) Alpha-galactosidase Proteins 0.000 description 1
- 241000282695 Saimiri Species 0.000 description 1
- 241000555028 Sternidius alpha Species 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
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 208000011589 adenoviridae infectious disease Diseases 0.000 description 1
- 210000004404 adrenal cortex Anatomy 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- DEGAKNSWVGKMLS-UHFFFAOYSA-N calcein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC(CN(CC(O)=O)CC(O)=O)=C(O)C=C1OC1=C2C=C(CN(CC(O)=O)CC(=O)O)C(O)=C1 DEGAKNSWVGKMLS-UHFFFAOYSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000008029 eradication Effects 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 238000002744 homologous recombination Methods 0.000 description 1
- 230000006801 homologous recombination Effects 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000009399 inbreeding Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000013011 mating Effects 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
- 238000000520 microinjection Methods 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 229960002378 oftasceine Drugs 0.000 description 1
- 238000009401 outcrossing Methods 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000000849 parathyroid Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 238000012340 reverse transcriptase PCR Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012868 site-directed mutagenesis technique Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001541 thymus gland Anatomy 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000005820 transferase reaction Methods 0.000 description 1
- 238000012250 transgenic expression Methods 0.000 description 1
- 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 1
- 230000001960 triggered effect Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
- C12N9/2465—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1) acting on alpha-galactose-glycoside bonds, e.g. alpha-galactosidase (3.2.1.22)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- 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
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Environmental Sciences (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Wood Science & Technology (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Biomedical Technology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US620095P | 1995-11-03 | 1995-11-03 | |
US60/006,200 | 1995-11-03 | ||
PCT/US1996/017695 WO1997016064A1 (fr) | 1995-11-03 | 1996-11-01 | Procedes et compositions de reduction du rejet de xenogreffe |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2000514641A true JP2000514641A (ja) | 2000-11-07 |
Family
ID=21719767
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP09517615A Pending JP2000514641A (ja) | 1995-11-03 | 1996-11-01 | 異種移植拒絶を低減するための方法および組成物 |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0877549A4 (fr) |
JP (1) | JP2000514641A (fr) |
AU (1) | AU7668696A (fr) |
IL (1) | IL124293A0 (fr) |
WO (1) | WO1997016064A1 (fr) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU1581899A (en) * | 1997-10-28 | 1999-05-17 | Biotransplant Incorporated | Nuclear transfer for production of transgenic animal embryo |
US6399578B1 (en) | 1998-12-09 | 2002-06-04 | La Jolla Pharmaceutical Company | Conjugates comprising galactose α1,3 galactosyl epitopes and methods of using same |
AU2003265415A1 (en) | 2002-08-14 | 2004-03-03 | Immerge Biotherapeutics, Inc. | Alpha(1,3)-GALACTOSYLTRANSFERASE NULL CELLS, METHODS OF SELECTING AND Alpha(1,3)-GALACTOSYLTRANSFERASE NULL SWINE PRODUCED THEREFROM |
US8106251B2 (en) | 2002-08-21 | 2012-01-31 | Revivicor, Inc. | Tissue products derived from porcine animals lacking any expression of functional alpha 1,3 galactosyltransferase |
EP1534819B1 (fr) | 2002-08-21 | 2009-12-09 | Revivicor, Inc. | Porcins ne presentant aucune expression de l'alpha 1,3-galactosyltransferase fonctionnelle |
EP1685148A2 (fr) | 2003-11-05 | 2006-08-02 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Proteine isogloboside 3 synthase porcine, adnc, organisation genomique, et region regulatrice |
ES2538819T3 (es) | 2009-07-30 | 2015-06-24 | F. Hoffmann-La Roche Ag | Procesamiento enzimático de anticuerpos |
US9420770B2 (en) | 2009-12-01 | 2016-08-23 | Indiana University Research & Technology Corporation | Methods of modulating thrombocytopenia and modified transgenic pigs |
CA2809632A1 (fr) | 2010-10-05 | 2012-04-12 | Monika Baehner | Anticorps dirige contre le tweak humain et leurs utilisations |
EP2764020B1 (fr) | 2011-10-05 | 2015-08-12 | F. Hoffmann-La Roche AG | Procédé de production d'anticorps de glycoforme g1 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5356804A (en) * | 1990-10-24 | 1994-10-18 | Mount Sinai School Of Medicine Of The City Of New York | Cloning and expression of biologically active human α-galactosidase A |
AU2233295A (en) * | 1994-04-13 | 1995-11-10 | Biotransplant Incorporated | Alpha(1,3) galactosyltransferase negative swine |
CA2192660A1 (fr) * | 1994-06-15 | 1995-12-21 | Mauro S. Sandrin | Procedes permettant de reduire le rejet suraigu d'heterogreffes |
-
1996
- 1996-11-01 AU AU76686/96A patent/AU7668696A/en not_active Abandoned
- 1996-11-01 WO PCT/US1996/017695 patent/WO1997016064A1/fr not_active Application Discontinuation
- 1996-11-01 EP EP96939544A patent/EP0877549A4/fr not_active Withdrawn
- 1996-11-01 JP JP09517615A patent/JP2000514641A/ja active Pending
- 1996-11-01 IL IL12429396A patent/IL124293A0/xx unknown
Also Published As
Publication number | Publication date |
---|---|
WO1997016064A1 (fr) | 1997-05-09 |
EP0877549A1 (fr) | 1998-11-18 |
IL124293A0 (en) | 1998-12-06 |
EP0877549A4 (fr) | 2002-01-02 |
AU7668696A (en) | 1997-05-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU727546B2 (en) | Transgenic animals for xenotransplantation with reduced antibody-mediated rejection | |
US6413769B1 (en) | α(1,3) galactosyltransferase negative porcine cells | |
US7931902B2 (en) | Gene disruptions, compositions and methods relating thereto | |
JP2009504183A5 (fr) | ||
CA2496761A1 (fr) | Porcins ne presentant aucune expression de l'alpha 1,3-galactosyltransferase fonctionnelle | |
KR101149475B1 (ko) | 이종 장기 이식용 미니 복제돼지 생산을 위한 유전자 조작된 세포주 및 그의 생산방법 | |
JPH08509870A (ja) | 特定のcd45イソ型タンパク質の発現を遮断するトランスジェニック哺乳動物 | |
JP2008510488A (ja) | 新規な遺伝子破壊、これに関する組成物と方法 | |
JPH10504707A (ja) | 異種移植片の超急性拒否反応を減少させる方法 | |
US6455037B1 (en) | Cells expressing an αgala nucleic acid and methods of xenotransplantation | |
JP7129426B2 (ja) | Mhcクラスiおよびmhcクラスiiを欠損しているnsgマウス | |
JP2000514641A (ja) | 異種移植拒絶を低減するための方法および組成物 | |
WO1997016064A9 (fr) | Procedes et compositions de reduction du rejet de xenogreffe | |
Charreau et al. | Protection against hyperacute xenograft rejection of transgenic rat hearts expressing human decay accelerating factor (DAF) transplanted into primates | |
WO2002015681A1 (fr) | Mammiferes transgeniques | |
AU637986B2 (en) | Transgenic animals for testing multidrug resistance | |
JPH10507070A (ja) | Ikarosトランスジェニック細胞及び動物 | |
US6642369B1 (en) | Nucleic acids involved in the responder phenotype and applications thereof | |
AU6970700A (en) | Method and compositions for the reduction of xenotransplantation rejection | |
KR20200119826A (ko) | 돼지 이종항원의 식별 | |
Murakami et al. | Porcine MCP gene promoter directs high level expression of human DAF (CD55) in transgenic mice | |
AU766519B2 (en) | alpha(1,3)-galactosyltransferase negative swine | |
WO2002081688A1 (fr) | Molecules d'adn codant pour la synthase d'igb3, et ses utilisations pour l'interruption des genes de glycosyltransferase dans des tissus et organes de xenogreffe | |
EP1535512A1 (fr) | Animal modele de maladie portant un gene etranger ppar$g(a) transfere et utilisation correspondante | |
Chung et al. | Remodeling of the Major Mouse Xenoantigen, Galα1-3Galβ1-4GIcNAc-R, by N-Acetylglucosaminyltransferase-III |