CA2507486A1 - .alpha.(1,3)-galactosyltransferase null cells, methods of selecting and .alpha.(1,3)-galactosyltransferase null swine produced therefrom - Google Patents
.alpha.(1,3)-galactosyltransferase null cells, methods of selecting and .alpha.(1,3)-galactosyltransferase null swine produced therefrom Download PDFInfo
- Publication number
- CA2507486A1 CA2507486A1 CA002507486A CA2507486A CA2507486A1 CA 2507486 A1 CA2507486 A1 CA 2507486A1 CA 002507486 A CA002507486 A CA 002507486A CA 2507486 A CA2507486 A CA 2507486A CA 2507486 A1 CA2507486 A1 CA 2507486A1
- Authority
- CA
- Canada
- Prior art keywords
- cells
- ggta1
- porcine
- galactose
- null
- 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.)
- Abandoned
Links
- 241000282898 Sus scrofa Species 0.000 title claims abstract description 91
- 238000000034 method Methods 0.000 title claims abstract description 59
- 210000004287 null lymphocyte Anatomy 0.000 title claims abstract description 42
- 210000004027 cell Anatomy 0.000 claims abstract description 191
- 101000856513 Homo sapiens Inactive N-acetyllactosaminide alpha-1,3-galactosyltransferase Proteins 0.000 claims abstract description 74
- 102100025509 Inactive N-acetyllactosaminide alpha-1,3-galactosyltransferase Human genes 0.000 claims abstract description 74
- 210000000056 organ Anatomy 0.000 claims abstract description 30
- 101150042360 GGTA1 gene Proteins 0.000 claims description 96
- 108700028369 Alleles Proteins 0.000 claims description 48
- 230000000295 complement effect Effects 0.000 claims description 31
- 238000011282 treatment Methods 0.000 claims description 31
- 210000000287 oocyte Anatomy 0.000 claims description 30
- 210000002950 fibroblast Anatomy 0.000 claims description 29
- 210000001161 mammalian embryo Anatomy 0.000 claims description 26
- 230000001605 fetal effect Effects 0.000 claims description 21
- 210000003754 fetus Anatomy 0.000 claims description 21
- 239000003446 ligand Substances 0.000 claims description 15
- 241000288906 Primates Species 0.000 claims description 14
- 230000000779 depleting effect Effects 0.000 claims description 13
- 239000011325 microbead Substances 0.000 claims description 12
- 230000012173 estrus Effects 0.000 claims description 11
- 230000016087 ovulation Effects 0.000 claims description 11
- 108090001090 Lectins Proteins 0.000 claims description 9
- 102000004856 Lectins Human genes 0.000 claims description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- FHIVAFMUCKRCQO-UHFFFAOYSA-N diazinon Chemical compound CCOP(=S)(OCC)OC1=CC(C)=NC(C(C)C)=N1 FHIVAFMUCKRCQO-UHFFFAOYSA-N 0.000 claims description 9
- 239000002523 lectin Substances 0.000 claims description 9
- 210000000130 stem cell Anatomy 0.000 claims description 5
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 claims description 4
- 230000001745 anti-biotin effect Effects 0.000 claims description 3
- 229960002685 biotin Drugs 0.000 claims description 3
- 239000011616 biotin Substances 0.000 claims description 3
- 239000012634 fragment Substances 0.000 claims description 3
- 235000020958 biotin Nutrition 0.000 claims description 2
- 210000002216 heart Anatomy 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 210000004185 liver Anatomy 0.000 claims description 2
- 210000000496 pancreas Anatomy 0.000 claims description 2
- 210000003491 skin Anatomy 0.000 claims description 2
- 210000001685 thyroid gland Anatomy 0.000 claims description 2
- YGEHCIVVZVBCLE-FSYGUOKUSA-N 3alpha-galactobiose Chemical compound OC[C@@H](O)[C@H](O)[C@@H]([C@@H](O)C=O)O[C@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O YGEHCIVVZVBCLE-FSYGUOKUSA-N 0.000 claims 1
- 108010008279 porcine alpha-1,3-galactosyltransferase 1 Proteins 0.000 claims 1
- 210000001519 tissue Anatomy 0.000 abstract description 17
- 238000002689 xenotransplantation Methods 0.000 abstract description 17
- 241000282414 Homo sapiens Species 0.000 abstract description 9
- 238000010353 genetic engineering Methods 0.000 abstract description 7
- 108090000623 proteins and genes Proteins 0.000 description 17
- 238000004458 analytical method Methods 0.000 description 16
- 238000010186 staining Methods 0.000 description 15
- 238000012546 transfer Methods 0.000 description 14
- 239000011324 bead Substances 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 10
- 238000002955 isolation Methods 0.000 description 10
- 238000000684 flow cytometry Methods 0.000 description 9
- 239000000872 buffer Substances 0.000 description 8
- 101150017040 I gene Proteins 0.000 description 7
- 210000002257 embryonic structure Anatomy 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 238000002054 transplantation Methods 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 238000002105 Southern blotting Methods 0.000 description 6
- 241000282887 Suidae Species 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 230000035935 pregnancy Effects 0.000 description 5
- 230000009261 transgenic effect Effects 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 102000012422 Collagen Type I Human genes 0.000 description 4
- 108010022452 Collagen Type I Proteins 0.000 description 4
- 241001504519 Papio ursinus Species 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000009089 cytolysis Effects 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 239000012091 fetal bovine serum Substances 0.000 description 4
- 238000002744 homologous recombination Methods 0.000 description 4
- 230000006801 homologous recombination Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 3
- 229930182566 Gentamicin Natural products 0.000 description 3
- 238000009395 breeding Methods 0.000 description 3
- 230000001488 breeding effect Effects 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 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 3
- 238000011331 genomic analysis Methods 0.000 description 3
- 238000003780 insertion Methods 0.000 description 3
- 230000037431 insertion Effects 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 210000004291 uterus Anatomy 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 238000010222 PCR analysis Methods 0.000 description 2
- 238000010240 RT-PCR analysis Methods 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 102000004142 Trypsin Human genes 0.000 description 2
- 108090000631 Trypsin Proteins 0.000 description 2
- 230000008827 biological function Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 210000000805 cytoplasm Anatomy 0.000 description 2
- 230000029087 digestion Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000005206 flow analysis Methods 0.000 description 2
- 125000002519 galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000012239 gene modification Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 230000005017 genetic modification Effects 0.000 description 2
- 235000013617 genetically modified food Nutrition 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 229940124589 immunosuppressive drug Drugs 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000001776 parthenogenetic effect Effects 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 238000007747 plating Methods 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 210000001082 somatic cell Anatomy 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 239000012588 trypsin Substances 0.000 description 2
- 238000009010 Bradford assay Methods 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 108010054576 Deoxyribonuclease EcoRI Proteins 0.000 description 1
- 102000007260 Deoxyribonuclease I Human genes 0.000 description 1
- 108010008532 Deoxyribonuclease I Proteins 0.000 description 1
- 108060003306 Galactosyltransferase Proteins 0.000 description 1
- 102000030902 Galactosyltransferase Human genes 0.000 description 1
- 241000282575 Gorilla Species 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 241001272567 Hominoidea Species 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 241000288903 Lemuridae Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 102100023315 N-acetyllactosaminide beta-1,6-N-acetylglucosaminyl-transferase Human genes 0.000 description 1
- 108010056664 N-acetyllactosaminide beta-1,6-N-acetylglucosaminyltransferase Proteins 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 108020005187 Oligonucleotide Probes Proteins 0.000 description 1
- 206010053159 Organ failure Diseases 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 108010006785 Taq Polymerase Proteins 0.000 description 1
- 241000288942 Tarsiidae 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
- 238000002835 absorbance Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000006727 cell loss Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 238000005138 cryopreservation Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 238000010363 gene targeting Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011813 knockout mouse model Methods 0.000 description 1
- 210000001821 langerhans cell Anatomy 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000002826 magnetic-activated cell sorting Methods 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000007479 molecular analysis Methods 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000002751 oligonucleotide probe Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 238000005406 washing 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
- A01K67/0276—Knock-out vertebrates
-
- 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
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, 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
- 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
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/873—Techniques for producing new embryos, e.g. nuclear transfer, manipulation of totipotent cells or production of chimeric embryos
- C12N15/877—Techniques for producing new mammalian cloned embryos
- C12N15/8778—Swine embryos
-
- 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
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0608—Germ cells
- C12N5/0611—Primordial germ cells, e.g. embryonic germ cells [EG]
-
- 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
- C12N9/10—Transferases (2.)
- C12N9/1048—Glycosyltransferases (2.4)
- C12N9/1051—Hexosyltransferases (2.4.1)
-
- 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
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
-
- 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
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/108—Swine
-
- 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
- A01K2267/00—Animals characterised by purpose
- A01K2267/02—Animal zootechnically ameliorated
- A01K2267/025—Animal producing cells or organs for transplantation
-
- 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
- C12N2517/00—Cells related to new breeds of animals
- C12N2517/02—Cells from transgenic animals
-
- 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
- C12N2517/00—Cells related to new breeds of animals
- C12N2517/04—Cells produced using nuclear transfer
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Developmental Biology & Embryology (AREA)
- Molecular Biology (AREA)
- Environmental Sciences (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Cell Biology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US40340502P | 2002-08-14 | 2002-08-14 | |
| US60/403,405 | 2002-08-14 | ||
| PCT/US2003/025199 WO2004016742A2 (en) | 2002-08-14 | 2003-08-13 | α(1,3)-GALACTOSYLTRANSFERASE NULL CELLS, METHODS OF SELECTING AND α(1,3)-GALACTOSYLTRANSFERASE NULL SWINE PRODUCED THEREFROM |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2507486A1 true CA2507486A1 (en) | 2004-02-26 |
Family
ID=31888232
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002507486A Abandoned CA2507486A1 (en) | 2002-08-14 | 2003-08-13 | .alpha.(1,3)-galactosyltransferase null cells, methods of selecting and .alpha.(1,3)-galactosyltransferase null swine produced therefrom |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US7547522B2 (https=) |
| EP (1) | EP1534066A4 (https=) |
| JP (1) | JP2005535343A (https=) |
| AU (1) | AU2003265415A1 (https=) |
| CA (1) | CA2507486A1 (https=) |
| WO (1) | WO2004016742A2 (https=) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020012660A1 (en) * | 1999-03-04 | 2002-01-31 | Alan Colman | Method of preparing a somatic cells for nuclear transfer |
| DK1534819T3 (da) * | 2002-08-21 | 2010-04-19 | Revivicor Inc | Griselignende dyr, som mangler enhver ekspression af funktionel alfa-1,3-galactosyltransferase |
| US7468273B2 (en) * | 2003-05-01 | 2008-12-23 | Meial Limited | Canine GHRH gene, polypeptides and methods of use |
| CA2528500A1 (en) | 2003-06-06 | 2004-12-16 | University Of Pittsburgh | Porcine cmp-n-acetylneuraminic acid hydroxylase gene |
| WO2005009134A1 (en) | 2003-07-21 | 2005-02-03 | Lifecell Corporation | ACELLULAR TISSUE MATRICES MADE FROM GALACTOSE α-1,3-GALACTOSE-DEFICIENT TISSUE |
| EP1685148A2 (en) | 2003-11-05 | 2006-08-02 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | PORCINE ISOGLOBOSIDE 3 SYNTHASE PROTEIN, cDNA, GENOMIC ORGANIZATION, AND REGULATORY REGION |
| US20070269412A1 (en) | 2003-12-02 | 2007-11-22 | Celavie Biosciences, Llc | Pluripotent cells |
| CN104721883A (zh) | 2004-03-17 | 2015-06-24 | 雷维维科公司 | 来源于缺乏任何功能性α1,3半乳糖基转移酶表达的动物的组织产品 |
| JP2006129736A (ja) * | 2004-11-02 | 2006-05-25 | Nippon Dobutsu Kogaku Kenkyusho:Kk | 異種移植用豚細胞、その選抜方法及び異種移植用豚 |
| CA2909775A1 (en) | 2005-08-09 | 2007-03-29 | Revivicor, Inc. | Transgenic ungulates expressing ctla4-ig and uses thereof |
| KR100943984B1 (ko) | 2007-11-23 | 2010-02-26 | 한국생명공학연구원 | 돼지 ＧＧＴＡ１ 유전자의 발현 억제를 위한 ｓｉＲＮＡ 및이를 포함하는 발현벡터 |
| WO2010019526A1 (en) * | 2008-08-14 | 2010-02-18 | Brent Lee | Dynamic filtration device using centrifugal force |
| US20100209399A1 (en) * | 2009-02-13 | 2010-08-19 | Celavie Biosciences, Llc | Brain-derived stem cells for repair of musculoskeletal system in vertebrate subjects |
| CA3104704A1 (en) | 2009-08-14 | 2011-02-17 | Revivicor, Inc. | Multi-transgenic pigs for diabetes treatment |
| US9420770B2 (en) | 2009-12-01 | 2016-08-23 | Indiana University Research & Technology Corporation | Methods of modulating thrombocytopenia and modified transgenic pigs |
| CN103492576A (zh) | 2011-02-14 | 2014-01-01 | 雷维维科公司 | 用于血管化异种移植物及其衍生物的异种移植的遗传修饰的猪 |
| JP2014520533A (ja) * | 2011-06-30 | 2014-08-25 | シグマ−アルドリッチ・カンパニー・リミテッド・ライアビリティ・カンパニー | Ｃｍｐ−ｎ−アセチルノイラミン酸ヒドロキシラーゼおよび／または糖タンパク質アルファ−１，３−ガラクトシルトランスフェラーゼを欠損する細胞 |
| US20140115728A1 (en) | 2012-10-24 | 2014-04-24 | A. Joseph Tector | Double knockout (gt/cmah-ko) pigs, organs and tissues |
| EP3065790B1 (en) | 2013-11-04 | 2020-10-28 | LifeCell Corporation | Methods of removing alpha-galactose |
| WO2018195402A1 (en) | 2017-04-20 | 2018-10-25 | Egenesis, Inc. | Methods for generating genetically modified animals |
| US10883084B2 (en) | 2018-10-05 | 2021-01-05 | Xenotherapeutics, Inc. | Personalized cells, tissues, and organs for transplantation from a humanized, bespoke, designated-pathogen free, (non-human) donor and methods and products relating to same |
| KR20210089659A (ko) | 2018-10-05 | 2021-07-16 | 제노세라퓨틱스, 인코포레이티드 | 이종이식 생성물 및 방법 |
| EP3945799A1 (en) | 2019-03-25 | 2022-02-09 | Xenotherapeutics, Inc. | Personalized cells, tissues, and organs for transplantation from a humanized, bespoke, designated-pathogen free, (non- human) donor and methods and products relating to same |
| JP2023551404A (ja) | 2020-11-20 | 2023-12-08 | レビビコア， インコーポレイテッド | 異種間移植のための成長ホルモン受容体ノックアウトを有する多重トランスジェニックブタ |
| KR20240099180A (ko) | 2021-09-20 | 2024-06-28 | 레비비코르 인코포레이션 | 이종이식을 위한 10개의 유전자 변형을 포함하는 다중전이유전자 돼지 |
| US20240294869A1 (en) | 2023-03-03 | 2024-09-05 | Nugift Medical Llc | Pig xenotransplants into humans without chronic immunosuppression |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4038236B2 (ja) | 1993-03-16 | 2008-01-23 | オースチン・リサーチ・インスティテュート | 異種移植治療におけるブタＧａ１α（１，３）ガラクトシルトランスフェラーゼの使用 |
| US6331658B1 (en) | 1993-04-20 | 2001-12-18 | Integris Baptist Medical Center, Inc. | Genetically engineered mammals for use as organ donors |
| US5849991A (en) | 1994-01-27 | 1998-12-15 | Bresatch Limited | Mice homozygous for an inactivated α 1,3-galactosyl transferase gene |
| JPH09508277A (ja) | 1994-01-27 | 1997-08-26 | ブレサゲン リミテッド | ヒト異種移植における超急性拒絶の管理のための物質及び方法 |
| DE69535752D1 (de) * | 1994-04-13 | 2008-06-26 | Biotransplant Inc | Alpha(1,3)galactosyltransferase-negatives schwein |
| US6166288A (en) | 1995-09-27 | 2000-12-26 | Nextran Inc. | Method of producing transgenic animals for xenotransplantation expressing both an enzyme masking or reducing the level of the gal epitope and a complement inhibitor |
| WO1997016064A1 (en) | 1995-11-03 | 1997-05-09 | The Mount Sinai Medical Center | Methods and compositions for the reduction of xenotransplantation rejection |
| WO2001088096A2 (en) | 2000-05-15 | 2001-11-22 | Geron Corporation | Ovine tissue for xenotransplantation |
-
2003
- 2003-08-13 AU AU2003265415A patent/AU2003265415A1/en not_active Abandoned
- 2003-08-13 JP JP2004529314A patent/JP2005535343A/ja active Pending
- 2003-08-13 EP EP03788393A patent/EP1534066A4/en not_active Withdrawn
- 2003-08-13 CA CA002507486A patent/CA2507486A1/en not_active Abandoned
- 2003-08-13 WO PCT/US2003/025199 patent/WO2004016742A2/en not_active Ceased
- 2003-08-13 US US10/524,381 patent/US7547522B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JP2005535343A (ja) | 2005-11-24 |
| WO2004016742A2 (en) | 2004-02-26 |
| EP1534066A2 (en) | 2005-06-01 |
| US7547522B2 (en) | 2009-06-16 |
| US20060242722A1 (en) | 2006-10-26 |
| WO2004016742A3 (en) | 2004-06-17 |
| AU2003265415A1 (en) | 2004-03-03 |
| EP1534066A4 (en) | 2008-01-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7547522B2 (en) | Method to enrich for α(1,3)-galactosyltransferase null pig cells | |
| EP0755402B1 (en) | Alpha(1,3) galactosyltransferase negative swine | |
| AU2003295322B2 (en) | Porcine animals lacking any expression of functional alpha 1,3 galactosyltransferase | |
| TW448032B (en) | Method for preparing hybridoma for generating human antibody | |
| JP2007533328A (ja) | トランスジェニック動物及びその用途 | |
| JP2025090688A (ja) | 向上した異種移植生存及び／又は耐性のための１つ以上の改変遺伝子を有する細胞、組織、器官、及び／又は動物 | |
| CN115003817A (zh) | 猪内源性逆转录病毒包膜C为阴性、GGTA1、CMAH、iGb3s及β4GalNT2基因被敲除并且表达人类CD46及TBM基因的异种器官移植用转基因克隆猪及其制备方法 | |
| WO2005003359A1 (ja) | トランスジェニック生物を作製する方法およびシステム | |
| US20060057719A1 (en) | Carbohydrate determinant selection system for homologous recombination | |
| JP2021511801A (ja) | ブタ異種抗原の同定 | |
| US20060015955A1 (en) | Alpha(1,3)Galactosyltransferase enzyme that assembles the Galalpha(1,3)Gal xenoantigen | |
| CA2279542A1 (en) | Tolerance to natural antibody antigens | |
| US10717991B2 (en) | Transgenic pig which simultaneously expresses HO-1 gene and TNFR1-Fc gene, and comprises knocked-out GGTA1 gene, and use thereof | |
| US20240189365A1 (en) | Glycan Targets of Serum IgG and IgM Antibodies | |
| KR101843427B1 (ko) | 돼지의 이소글로보트리헥소실세라마이드 신타제 넉아웃 세포주 및 그의 제조 방법 | |
| WO2006048954A1 (ja) | 異種移植用豚細胞、その選抜方法及び異種移植用豚 | |
| AU766519B2 (en) | alpha(1,3)-galactosyltransferase negative swine | |
| KR20260050358A (ko) | 유전자 변형된 돼지 세포, 유전자 변형된 돼지 및 이의 생산 방법 | |
| Butler | Nuclease-based editing in the porcine genome: a strategy to facilitate porcine-to human xenotransplantation | |
| KR20070018075A (ko) | 트랜스제닉 동물 및 그의 용도 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |