DE60121372T2 - Methoden zur modifikation eukaryotischer zellen - Google Patents
Methoden zur modifikation eukaryotischer zellen Download PDFInfo
- Publication number
- DE60121372T2 DE60121372T2 DE60121372T DE60121372T DE60121372T2 DE 60121372 T2 DE60121372 T2 DE 60121372T2 DE 60121372 T DE60121372 T DE 60121372T DE 60121372 T DE60121372 T DE 60121372T DE 60121372 T2 DE60121372 T2 DE 60121372T2
- Authority
- DE
- Germany
- Prior art keywords
- gene
- cells
- chromosomal locus
- ltvec
- 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.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims abstract description 96
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 150
- 210000004027 cell Anatomy 0.000 claims abstract description 99
- 210000003527 eukaryotic cell Anatomy 0.000 claims abstract description 87
- 230000002759 chromosomal effect Effects 0.000 claims abstract description 70
- 239000013598 vector Substances 0.000 claims abstract description 64
- 230000006801 homologous recombination Effects 0.000 claims abstract description 58
- 238000002744 homologous recombination Methods 0.000 claims abstract description 58
- 239000012634 fragment Substances 0.000 claims abstract description 52
- 238000012239 gene modification Methods 0.000 claims abstract description 20
- 230000005017 genetic modification Effects 0.000 claims abstract description 19
- 235000013617 genetically modified food Nutrition 0.000 claims abstract description 19
- 108020004414 DNA Proteins 0.000 claims description 72
- 230000004048 modification Effects 0.000 claims description 71
- 238000012986 modification Methods 0.000 claims description 71
- 108700028369 Alleles Proteins 0.000 claims description 49
- 239000000523 sample Substances 0.000 claims description 36
- 230000001580 bacterial effect Effects 0.000 claims description 24
- 108091026890 Coding region Proteins 0.000 claims description 23
- 238000012217 deletion Methods 0.000 claims description 21
- 230000037430 deletion Effects 0.000 claims description 21
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 21
- 238000003780 insertion Methods 0.000 claims description 16
- 230000037431 insertion Effects 0.000 claims description 16
- 238000012207 quantitative assay Methods 0.000 claims description 16
- 238000003753 real-time PCR Methods 0.000 claims description 16
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 13
- 230000002068 genetic effect Effects 0.000 claims description 13
- 238000009396 hybridization Methods 0.000 claims description 13
- 230000001105 regulatory effect Effects 0.000 claims description 12
- 241000283984 Rodentia Species 0.000 claims description 10
- 210000001161 mammalian embryo Anatomy 0.000 claims description 9
- 102000004169 proteins and genes Human genes 0.000 claims description 9
- 241000894007 species Species 0.000 claims description 9
- 210000000130 stem cell Anatomy 0.000 claims description 9
- 230000004075 alteration Effects 0.000 claims description 6
- 230000004927 fusion Effects 0.000 claims description 5
- 238000006467 substitution reaction Methods 0.000 claims description 5
- 230000004544 DNA amplification Effects 0.000 claims description 3
- 230000001588 bifunctional effect Effects 0.000 claims description 3
- 230000000052 comparative effect Effects 0.000 claims description 3
- 230000008685 targeting Effects 0.000 abstract description 81
- 238000013459 approach Methods 0.000 abstract description 27
- 241000699666 Mus <mouse, genus> Species 0.000 description 30
- 238000005516 engineering process Methods 0.000 description 27
- 238000003556 assay Methods 0.000 description 25
- 238000012216 screening Methods 0.000 description 20
- 238000003752 polymerase chain reaction Methods 0.000 description 19
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 17
- 150000007523 nucleic acids Chemical class 0.000 description 15
- 230000008901 benefit Effects 0.000 description 14
- 108020004707 nucleic acids Proteins 0.000 description 13
- 102000039446 nucleic acids Human genes 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 12
- 239000003550 marker Substances 0.000 description 12
- 239000002773 nucleotide Substances 0.000 description 11
- 125000003729 nucleotide group Chemical group 0.000 description 11
- 241000700159 Rattus Species 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 238000010276 construction Methods 0.000 description 10
- 238000010369 molecular cloning Methods 0.000 description 10
- 238000011144 upstream manufacturing Methods 0.000 description 10
- 210000002459 blastocyst Anatomy 0.000 description 8
- 210000000349 chromosome Anatomy 0.000 description 8
- 108091008146 restriction endonucleases Proteins 0.000 description 8
- 206010003694 Atrophy Diseases 0.000 description 7
- 102000011755 Phosphoglycerate Kinase Human genes 0.000 description 7
- 108700008625 Reporter Genes Proteins 0.000 description 7
- 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 7
- 230000037444 atrophy Effects 0.000 description 7
- 238000004520 electroporation Methods 0.000 description 7
- 210000003205 muscle Anatomy 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 7
- 241000588724 Escherichia coli Species 0.000 description 6
- 108091081024 Start codon Proteins 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 238000011813 knockout mouse model Methods 0.000 description 6
- 108010025815 Kanamycin Kinase Proteins 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 4
- 206010028289 Muscle atrophy Diseases 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 230000020763 muscle atrophy Effects 0.000 description 4
- 201000000585 muscular atrophy Diseases 0.000 description 4
- 230000008488 polyadenylation Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 210000001938 protoplast Anatomy 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 3
- 102000002322 Egg Proteins Human genes 0.000 description 3
- 108010000912 Egg Proteins Proteins 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 101100356230 Escherichia coli (strain K12) recT gene Proteins 0.000 description 3
- 241001045988 Neogene Species 0.000 description 3
- 238000002105 Southern blotting Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000002638 denervation Effects 0.000 description 3
- 238000003209 gene knockout Methods 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 101150091879 neo gene Proteins 0.000 description 3
- 210000004681 ovum Anatomy 0.000 description 3
- 230000035935 pregnancy Effects 0.000 description 3
- 210000003497 sciatic nerve Anatomy 0.000 description 3
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 3
- 238000012795 verification Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 101100355997 Bacillus subtilis (strain 168) recA gene Proteins 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 108010051219 Cre recombinase Proteins 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- 101100301301 Escherichia coli (strain K12) recE gene Proteins 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- 108060002716 Exonuclease Proteins 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 108091036066 Three prime untranslated region Proteins 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 102000005936 beta-Galactosidase Human genes 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000008045 co-localization Effects 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- 102000013165 exonuclease Human genes 0.000 description 2
- 238000003198 gene knock in Methods 0.000 description 2
- 238000010363 gene targeting Methods 0.000 description 2
- 238000007901 in situ hybridization Methods 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- 101150066555 lacZ gene Proteins 0.000 description 2
- 210000003141 lower extremity Anatomy 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 230000031864 metaphase Effects 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 101150047627 pgk gene Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- CXNPLSGKWMLZPZ-GIFSMMMISA-N (2r,3r,6s)-3-[[(3s)-3-amino-5-[carbamimidoyl(methyl)amino]pentanoyl]amino]-6-(4-amino-2-oxopyrimidin-1-yl)-3,6-dihydro-2h-pyran-2-carboxylic acid Chemical compound O1[C@@H](C(O)=O)[C@H](NC(=O)C[C@@H](N)CCN(C)C(N)=N)C=C[C@H]1N1C(=O)N=C(N)C=C1 CXNPLSGKWMLZPZ-GIFSMMMISA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- 108020003215 DNA Probes Proteins 0.000 description 1
- 239000003298 DNA probe Substances 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 101001091269 Escherichia coli Hygromycin-B 4-O-kinase Proteins 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- 102100040669 F-box only protein 32 Human genes 0.000 description 1
- 101710191029 F-box only protein 32 Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000817629 Homo sapiens Dymeclin Proteins 0.000 description 1
- GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 108010091086 Recombinases Proteins 0.000 description 1
- 102000018120 Recombinases Human genes 0.000 description 1
- 102100021941 Sorcin Human genes 0.000 description 1
- 101710089292 Sorcin Proteins 0.000 description 1
- 101001091268 Streptomyces hygroscopicus Hygromycin-B 7''-O-kinase Proteins 0.000 description 1
- 208000035199 Tetraploidy Diseases 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 210000002593 Y chromosome Anatomy 0.000 description 1
- 241000209149 Zea Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 210000003578 bacterial chromosome Anatomy 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- CXNPLSGKWMLZPZ-UHFFFAOYSA-N blasticidin-S Natural products O1C(C(O)=O)C(NC(=O)CC(N)CCN(C)C(N)=N)C=CC1N1C(=O)N=C(N)C=C1 CXNPLSGKWMLZPZ-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
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000003869 genetically modified organism Nutrition 0.000 description 1
- 238000012268 genome sequencing Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 210000001624 hip Anatomy 0.000 description 1
- 238000011905 homologation Methods 0.000 description 1
- GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 1
- 229940097277 hygromycin b Drugs 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 238000013493 large scale plasmid preparation Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000003632 microfilament Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 238000003906 pulsed field gel electrophoresis Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 210000003765 sex chromosome Anatomy 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 238000010408 sweeping Methods 0.000 description 1
- 230000009897 systematic effect Effects 0.000 description 1
- 238000010809 targeting technique Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009261 transgenic effect Effects 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
- 238000009966 trimming Methods 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 230000000007 visual effect Effects 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
-
- 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
- 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
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
- C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
-
- 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
- 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
- A01K2227/105—Murine
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Environmental Sciences (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Biochemistry (AREA)
- Mycology (AREA)
- Cell Biology (AREA)
- Biodiversity & Conservation Biology (AREA)
- Animal Husbandry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24466500P | 2000-10-31 | 2000-10-31 | |
| US244665P | 2000-10-31 | ||
| US732234 | 2000-12-07 | ||
| US09/732,234 US6586251B2 (en) | 2000-10-31 | 2000-12-07 | Methods of modifying eukaryotic cells |
| PCT/US2001/045375 WO2002036789A2 (en) | 2000-10-31 | 2001-10-31 | Methods of modifying eukaryotic cells |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60121372D1 DE60121372D1 (de) | 2006-08-17 |
| DE60121372T2 true DE60121372T2 (de) | 2007-07-26 |
Family
ID=26936709
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60121372T Expired - Lifetime DE60121372T2 (de) | 2000-10-31 | 2001-10-31 | Methoden zur modifikation eukaryotischer zellen |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US6586251B2 (cg-RX-API-DMAC7.html) |
| EP (1) | EP1399575B1 (cg-RX-API-DMAC7.html) |
| JP (7) | JP5339566B2 (cg-RX-API-DMAC7.html) |
| KR (1) | KR100833136B1 (cg-RX-API-DMAC7.html) |
| CN (1) | CN100497642C (cg-RX-API-DMAC7.html) |
| AT (1) | ATE332388T1 (cg-RX-API-DMAC7.html) |
| AU (2) | AU2004802A (cg-RX-API-DMAC7.html) |
| BR (1) | BRPI0115096B1 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2426398C (cg-RX-API-DMAC7.html) |
| CZ (1) | CZ304856B6 (cg-RX-API-DMAC7.html) |
| DE (1) | DE60121372T2 (cg-RX-API-DMAC7.html) |
| HU (1) | HU227639B1 (cg-RX-API-DMAC7.html) |
| MX (1) | MXPA03003797A (cg-RX-API-DMAC7.html) |
| NO (1) | NO332300B1 (cg-RX-API-DMAC7.html) |
| NZ (1) | NZ525511A (cg-RX-API-DMAC7.html) |
| PL (1) | PL204759B1 (cg-RX-API-DMAC7.html) |
| RU (1) | RU2290441C2 (cg-RX-API-DMAC7.html) |
| WO (1) | WO2002036789A2 (cg-RX-API-DMAC7.html) |
Families Citing this family (215)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6908744B1 (en) * | 2000-03-14 | 2005-06-21 | Regeneron Pharmaceuticals, Inc. | Methods of stimulating cartilage formation |
| DK1311661T3 (da) * | 2000-08-14 | 2012-11-26 | Us Gov Health & Human Serv | Forøget homolog rekombination medieret ved lambda-rekombinationsproteiner |
| US6586251B2 (en) * | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US20050144655A1 (en) | 2000-10-31 | 2005-06-30 | Economides Aris N. | Methods of modifying eukaryotic cells |
| GB0110029D0 (en) | 2001-04-24 | 2001-06-13 | Grosveld Frank | Transgenic animal |
| CA2684022C (en) | 2002-05-17 | 2014-09-23 | Mount Sinai School Of Medicine Of New York University | Mesoderm and definitive endoderm cell populations |
| CN105884893A (zh) | 2002-07-18 | 2016-08-24 | 莫鲁斯有限公司 | 抗体混合物的重组生产 |
| USRE47770E1 (en) | 2002-07-18 | 2019-12-17 | Merus N.V. | Recombinant production of mixtures of antibodies |
| EP1539946A4 (en) * | 2002-09-09 | 2006-03-15 | California Inst Of Techn | METHOD AND COMPOSITIONS FOR PRODUCING HUMANIZED MICE |
| WO2004067725A2 (en) * | 2003-01-30 | 2004-08-12 | Regeneron Pharmaceuticals, Inc. | Methods of identifying modulators of nmur2-mediated activity |
| EP2395017A3 (en) | 2003-05-30 | 2012-12-19 | Merus B.V. | Design and use of paired variable regions of specific binding molecules |
| US20100069614A1 (en) | 2008-06-27 | 2010-03-18 | Merus B.V. | Antibody producing non-human mammals |
| PL1802193T3 (pl) | 2004-10-19 | 2014-09-30 | Regeneron Pharma | Sposób wytwarzania myszy homozygotycznej pod względem modyfikacji genetycznej |
| US20060117396A1 (en) * | 2004-11-30 | 2006-06-01 | Murphy Andrew J | Assay methods for identifying modulators of OPSDL3 and transgenic knockouts |
| JP5721951B2 (ja) | 2007-03-22 | 2015-05-20 | バイオジェン アイデック マサチューセッツ インコーポレイテッド | 抗体、抗体誘導体、および抗体断片を含む、cd154に特異的に結合する結合タンパク質ならびにその使用 |
| SI2602323T1 (en) | 2007-06-01 | 2018-05-31 | Open Monoclonal Technology, Inc. | Compositions and procedures for inhibiting endogenous immunoglobin gene and the formation of transgenic human idiopathic antibodies |
| US20110119779A1 (en) * | 2007-12-10 | 2011-05-19 | Aliva Biopharmaceuticals, Inc. | Methods for sequential replacement of targeted region by homologous recombination |
| JP2011518555A (ja) * | 2008-04-14 | 2011-06-30 | サンガモ バイオサイエンシーズ, インコーポレイテッド | 標的組込みのための線形ドナーコンストラクト |
| US20090328240A1 (en) * | 2008-06-24 | 2009-12-31 | Sing George L | Genetically modified mice as predictors of immune response |
| DE102008002715A1 (de) * | 2008-06-27 | 2009-12-31 | Evonik Röhm Gmbh | 2-Hydroxyisobuttersäure produzierende rekombinante Zelle |
| DK2346994T3 (da) | 2008-09-30 | 2022-02-28 | Ablexis Llc | Knock-in-mus til fremstilling af kimære antistoffer |
| US9445581B2 (en) | 2012-03-28 | 2016-09-20 | Kymab Limited | Animal models and therapeutic molecules |
| EP2517556B2 (en) | 2009-07-08 | 2023-03-22 | Kymab Limited | Site-Specific Recombination Method, Rodents & Rodent Cells capable of Expressing Chimaeric Antibodies or Chains |
| DK3417701T3 (da) | 2009-10-06 | 2022-03-14 | Regeneron Pharma | Genmodificerede mus og indpodning |
| JP5908405B2 (ja) | 2009-10-29 | 2016-04-26 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | 多機能性対立遺伝子 |
| DK2509409T3 (en) | 2009-12-10 | 2016-11-14 | Regeneron Pharma | MICE, WHICH PRODUCES HEAVY CHAIN ANTIBODIES |
| EP3336102A3 (en) | 2009-12-21 | 2018-08-01 | Regeneron Pharmaceuticals, Inc. | Humanized fc gamma r mice |
| WO2011097603A1 (en) | 2010-02-08 | 2011-08-11 | Regeneron Pharmaceuticals, Inc. | Common light chain mouse |
| US20130045492A1 (en) | 2010-02-08 | 2013-02-21 | Regeneron Pharmaceuticals, Inc. | Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain |
| US9796788B2 (en) | 2010-02-08 | 2017-10-24 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
| US20120021409A1 (en) | 2010-02-08 | 2012-01-26 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
| KR102004106B1 (ko) | 2010-03-31 | 2019-07-25 | 아블렉시스, 엘엘씨 | 키메라 항체의 제조를 위한 비-인간 동물의 유전적 조작 |
| US9242014B2 (en) | 2010-06-15 | 2016-01-26 | The Regents Of The University Of California | Receptor tyrosine kinase-like orphan receptor 1 (ROR1) single chain Fv antibody fragment conjugates and methods of use thereof |
| SMT201900241T1 (it) | 2010-06-22 | 2019-05-10 | Regeneron Pharma | Topi esprimenti una catena leggera ibrida di immunoglobulina con una regione variabile umana |
| US10662256B2 (en) | 2010-07-26 | 2020-05-26 | Trianni, Inc. | Transgenic mammals and methods of use thereof |
| DK2597945T3 (da) | 2010-07-26 | 2020-09-21 | Trianni Inc | Transgene dyr og fremgangsmåder til anvendelse deraf |
| US10793829B2 (en) | 2010-07-26 | 2020-10-06 | Trianni, Inc. | Transgenic mammals and methods of use thereof |
| RS55495B1 (sr) | 2010-08-02 | 2017-04-28 | Regeneron Pharma | Miševi koji stvaraju vezujuće proteine koji sadrže vl domene |
| EP2638155A1 (en) | 2010-11-08 | 2013-09-18 | Kymab Limited | Cells & vertebrates for enhanced somatic hypermutation and class switch recombination |
| DK2663579T3 (en) | 2011-01-14 | 2017-07-31 | Univ California | THERAPEUTIC ANTIBODIES AGAINST ROR-1 PROTEIN AND PROCEDURES FOR USE THEREOF |
| MX338971B (es) | 2011-02-15 | 2016-05-06 | Inst Res Biomedicine Irb | Ratones de m-csf humanizada. |
| US10920242B2 (en) | 2011-02-25 | 2021-02-16 | Recombinetics, Inc. | Non-meiotic allele introgression |
| HRP20230526T1 (hr) | 2011-02-25 | 2023-09-01 | Regeneron Pharmaceuticals, Inc. | Adam6 miševi |
| EP2631654B1 (en) | 2011-05-12 | 2015-04-15 | Regeneron Pharmaceuticals, Inc. | Neuropeptide release assay for sodium channels |
| SI3865581T1 (sl) | 2011-08-05 | 2024-12-31 | Regeneron Pharmaceuticals, Inc. | Miši s humanizirano univerzalno lahko verigo |
| JP2014531452A (ja) | 2011-09-19 | 2014-11-27 | カイマブ・リミテッド | 動物、レパートリーおよび方法 |
| CA2846319A1 (en) | 2011-09-19 | 2013-03-28 | Kymab Limited | Antibodies, variable domains & chains tailored for human use |
| EP2761008A1 (en) | 2011-09-26 | 2014-08-06 | Kymab Limited | Chimaeric surrogate light chains (slc) comprising human vpreb |
| SG10202010120XA (en) | 2011-10-17 | 2020-11-27 | Regeneron Pharma | Restricted immunoglobulin heavy chain mice |
| US9591835B2 (en) | 2011-10-28 | 2017-03-14 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
| US9043996B2 (en) | 2011-10-28 | 2015-06-02 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
| LT3262932T (lt) | 2011-10-28 | 2019-08-26 | Regeneron Pharmaceuticals, Inc. | Pelės su genetiškai modifikuotu pagrindiniu histosuderinamumo kompleksu |
| LT3590332T (lt) | 2011-10-28 | 2022-08-10 | Regeneron Pharmaceuticals, Inc. | Genetiškai modifikuotos pelės, ekspresuojančios chimerines pagrindinio audinių dermės komplekso (mhc) ii molekules |
| IN2014CN03890A (cg-RX-API-DMAC7.html) | 2011-10-28 | 2015-10-16 | Regeneron Pharma | |
| GB2496375A (en) | 2011-10-28 | 2013-05-15 | Kymab Ltd | A non-human assay vertebrate comprising human antibody loci and human epitope knock-in, and uses thereof |
| AU2012332894A1 (en) | 2011-10-31 | 2014-05-08 | Merck Sharp & Dohme Corp. | Nano-suspension process |
| GB201122047D0 (en) | 2011-12-21 | 2012-02-01 | Kymab Ltd | Transgenic animals |
| US9253965B2 (en) | 2012-03-28 | 2016-02-09 | Kymab Limited | Animal models and therapeutic molecules |
| PL2793567T3 (pl) | 2011-12-20 | 2019-09-30 | Regeneron Pharmaceuticals, Inc. | Myszy z humanizowanym łańcuchem lekkim |
| PL3597038T3 (pl) | 2012-02-01 | 2021-11-08 | Regeneron Pharmaceuticals, Inc. | Humanizowane gryzonie wykazujące ekspresję łańcuchów ciężkich zawierających domeny vl |
| AU2013204140B2 (en) | 2012-03-06 | 2016-01-28 | Regeneron Pharmaceuticals, Inc. | Common light chain mouse |
| RU2644684C2 (ru) | 2012-03-16 | 2018-02-13 | Регенерон Фармасьютикалз, Инк. | Антитела со встроенным в легкие цепи гистидином и генетически модифицированные отличные от человека животные для их получения |
| US20140013456A1 (en) | 2012-03-16 | 2014-01-09 | Regeneron Pharmaceuticals, Inc. | Histidine Engineered Light Chain Antibodies and Genetically Modified Non-Human Animals for Generating the Same |
| HUE045537T2 (hu) | 2012-03-16 | 2019-12-30 | Regeneron Pharma | PH-érzékeny immunglobulin-szekvenciákat expresszáló rágcsálók |
| AU2013204581B2 (en) | 2012-03-16 | 2015-06-25 | Regeneron Pharmaceuticals, Inc. | Non-human animals expressing pH-sensitive immunoglobulin sequences |
| GB2502127A (en) | 2012-05-17 | 2013-11-20 | Kymab Ltd | Multivalent antibodies and in vivo methods for their production |
| US10251377B2 (en) | 2012-03-28 | 2019-04-09 | Kymab Limited | Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies |
| JP2015512635A (ja) | 2012-03-28 | 2015-04-30 | カイマブ・リミテッド | クラススイッチした完全ヒト抗体の発現のためのトランスジェニック非−ヒト脊椎動物 |
| PT2847335T (pt) | 2012-04-25 | 2018-09-28 | Regeneron Pharma | Alvejamento mediado por nuclease com vetores de alvejamento grandes |
| CN104540383B (zh) | 2012-06-12 | 2017-08-29 | 瑞泽恩制药公司 | 具有受限制的免疫球蛋白重链基因座的人源化非人动物 |
| AR091482A1 (es) * | 2012-06-21 | 2015-02-04 | Recombinetics Inc | Celulas modificadas geneticamente y metodos par su obtencion |
| KR102274722B1 (ko) | 2012-08-23 | 2021-07-09 | 어젠시스 인코포레이티드 | 158p1d7 단백질에 결합하는 항체 |
| ES2992753T3 (en) | 2012-08-24 | 2024-12-17 | Univ California | Antibodies and vaccines for use in treating ror1 cancers and inhibiting metastasis |
| CN120718856A (zh) | 2012-09-07 | 2025-09-30 | 再生元制药公司 | 经遗传修饰的非人动物及其使用方法 |
| UA118090C2 (uk) * | 2012-09-07 | 2018-11-26 | ДАУ АГРОСАЙЄНСІЗ ЕлЕлСі | Спосіб інтегрування послідовності нуклеїнової кислоти, що представляє інтерес, у ген fad2 у клітині сої та специфічний для локусу fad2 білок, що зв'язується, здатний індукувати спрямований розрив |
| ES2748662T3 (es) | 2012-11-05 | 2020-03-17 | Institute For Res In Biomedicine Irb | Roedores inmunodeficientes modificados genéticamente y métodos de uso de los mismos |
| EP3561050B1 (en) | 2013-02-20 | 2021-12-08 | Regeneron Pharmaceuticals, Inc. | Genetic modification of rats |
| SMT201900429T1 (it) | 2013-02-20 | 2019-09-09 | Regeneron Pharma | Topi esprimenti co-recettori umanizzati linfociti t |
| WO2014130690A1 (en) * | 2013-02-20 | 2014-08-28 | Regeneron Pharmaceuticals, Inc. | Non-human animals with modified immunoglobulin heavy chain sequences |
| US20150342163A1 (en) | 2013-02-22 | 2015-12-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex mice |
| EP2958937B1 (en) | 2013-02-22 | 2018-08-15 | Regeneron Pharmaceuticals, Inc. | Mice expressing humanized major histocompatibility complex |
| JP6456350B2 (ja) | 2013-03-11 | 2019-01-23 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | キメラ主要組織適合複合体(mhc)クラスii分子を発現する遺伝子導入マウス |
| WO2014164640A1 (en) | 2013-03-11 | 2014-10-09 | Regeneron Pharmaceuticals, Inc. | Transgenic mice expressing chimeric major histocompatibility complex (mhc) class i molecules |
| CA2903696A1 (en) | 2013-03-13 | 2014-10-02 | Regeneron Pharmaceuticals, Inc. | Common light chain mouse |
| EP4545567A3 (en) | 2013-03-13 | 2025-08-13 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
| US9788534B2 (en) | 2013-03-18 | 2017-10-17 | Kymab Limited | Animal models and therapeutic molecules |
| HUE040575T2 (hu) * | 2013-04-16 | 2019-03-28 | Regeneron Pharma | A patkány genom célzott módosítása |
| US9783618B2 (en) | 2013-05-01 | 2017-10-10 | Kymab Limited | Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics |
| US11707056B2 (en) | 2013-05-02 | 2023-07-25 | Kymab Limited | Animals, repertoires and methods |
| US9783593B2 (en) | 2013-05-02 | 2017-10-10 | Kymab Limited | Antibodies, variable domains and chains tailored for human use |
| TWI646108B (zh) | 2013-08-01 | 2019-01-01 | 艾澤西公司 | 結合至cd37蛋白質之抗體藥物結合物(adc) |
| KR102138723B1 (ko) | 2013-08-07 | 2020-07-29 | 리제너론 파마슈티칼스 인코포레이티드 | Lincrna-결핍 비인간 동물 |
| LT3046412T (lt) | 2013-09-18 | 2019-07-25 | Regeneron Pharmaceuticals, Inc. | Histidino pakeitimus lengvoje grandinėje turintys antikūnai ir genetiškai modifikuoti gyvūnai, išskyrus žmogų, išvesti jų gamybai |
| DK4269430T3 (da) | 2013-09-23 | 2025-08-18 | Regeneron Pharma | Ikke-menneskelige dyr, der har et humaniseret signalregulerende proteingen |
| ES2993142T3 (en) | 2013-10-01 | 2024-12-23 | Kymab Ltd | Animal models and therapeutic molecules |
| KR102173297B1 (ko) | 2013-11-19 | 2020-11-03 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화된 증식-유도 리간드 유전자를 가지고 있는 비-인간 동물 |
| MY183188A (en) | 2013-11-19 | 2021-02-18 | Regeneron Pharma | Non-human animals having a humanized b-cell activating factor gene |
| US9546384B2 (en) * | 2013-12-11 | 2017-01-17 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for the targeted modification of a mouse genome |
| SMT201800653T1 (it) | 2013-12-11 | 2019-01-11 | Regeneron Pharma | Metodi e composizioni per la modificazione indirizzata a bersaglio di un genoma |
| WO2015108102A1 (ja) | 2014-01-15 | 2015-07-23 | 国立大学法人 群馬大学 | Atp可視化動物およびその用途 |
| TWI681969B (zh) * | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對pd-1的人類抗體 |
| ES2872475T3 (es) | 2014-03-21 | 2021-11-02 | Regeneron Pharma | Animales no humanos que producen proteínas de unión de dominio único |
| WO2015143406A2 (en) | 2014-03-21 | 2015-09-24 | Regeneron Pharmaceuticals, Inc. | Vl antigen binding proteins exhibiting distinct binding characteristics |
| EP4306648A3 (en) | 2014-05-19 | 2024-04-17 | Regeneron Pharmaceuticals, Inc. | Genetically modified mice expressing human epo |
| US9497945B2 (en) | 2014-05-30 | 2016-11-22 | Regeneron Pharmaceuticals, Inc. | Humanized dipeptidyl peptidase IV (DPP4) animals |
| LT3152312T (lt) | 2014-06-06 | 2020-04-27 | Regeneron Pharmaceuticals, Inc. | Tikslinio lokuso modifikavimo būdai ir kompozicijos |
| WO2015196051A1 (en) | 2014-06-19 | 2015-12-23 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized programmed cell death 1 gene |
| JP6336140B2 (ja) | 2014-06-23 | 2018-06-06 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | ヌクレアーゼ媒介dnaアセンブリ |
| EP3461885B1 (en) | 2014-06-26 | 2021-10-20 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for targeted genetic modifications and methods of use |
| JP2017529841A (ja) | 2014-09-19 | 2017-10-12 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | キメラ抗原受容体 |
| JP2017536811A (ja) | 2014-10-15 | 2017-12-14 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | 多能性細胞の樹立又は維持のための方法及び組成物 |
| HUE044907T2 (hu) * | 2014-11-21 | 2019-11-28 | Regeneron Pharma | Módszerek és készítmények célzott genetikai módosításhoz, párosított mutató RNS-ek használatával |
| RS63410B1 (sr) | 2014-11-24 | 2022-08-31 | Regeneron Pharma | Ne-humane životinje koje eksprimiraju humanizovani cd3 kompleks |
| BR112017010490A2 (pt) | 2014-12-05 | 2018-04-03 | Regeneron Pharma | roedor, polipeptídeo cd47, célula ou tecido de roedor isolado, célula-tronco emprionária de roedor, embrião de roedor, e, métodos de produzir um roedor, de fornecimento de um roedor, de enxerto de células humanas em um roedor, de avaliação de eficácia terapêutica de uma droga direcionada a células humanas e de avaliar as propriedades farmacocinéticas, de avaliar a toxicidade específica e inespecífica de uma droga direcionada ao cd47 humano. |
| LT3230320T (lt) | 2014-12-09 | 2021-01-11 | Regeneron Pharmaceuticals, Inc. | Gyvūnai, išskyrus žmogų, turintys humanizuotą diferenciacijos klasterio 274 geną |
| NZ732895A (en) * | 2014-12-19 | 2022-05-27 | Regeneron Pharma | Methods and compositions for targeted genetic modification through single-step multiple targeting |
| UA122331C2 (uk) | 2015-03-09 | 2020-10-26 | Едженсіс, Інк. | Антитіло проти flt3 та кон'югат антитіло-лікарський засіб (adc), який зв'язується з білком flt3 |
| US10285387B2 (en) | 2015-03-16 | 2019-05-14 | Regeneron Pharmaceuticals, Inc. | Non-human animal exhibiting diminished upper and lower motor neuron function and sensory perception |
| JP2018508224A (ja) | 2015-03-19 | 2018-03-29 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | 抗原を結合する軽鎖可変領域を選択する非ヒト動物 |
| DK3280257T3 (da) | 2015-04-06 | 2023-09-04 | Regeneron Pharma | Humaniseret T-celle-formidlet immunrespons i ikke-humane dyr |
| PT3282835T (pt) | 2015-04-13 | 2023-07-25 | Univ Yale | Ratinhos knockin de sirpa-il15 humanizadas e métodos de utilização dos mesmos |
| JP6913030B2 (ja) | 2015-05-18 | 2021-08-04 | アジェンシス,インコーポレイテッド | Axlタンパク質に結合する抗体 |
| US10395759B2 (en) | 2015-05-18 | 2019-08-27 | Regeneron Pharmaceuticals, Inc. | Methods and systems for copy number variant detection |
| US10787516B2 (en) | 2015-05-18 | 2020-09-29 | Agensys, Inc. | Antibodies that bind to AXL proteins |
| ES3009538T3 (en) | 2015-05-29 | 2025-03-27 | Regeneron Pharma | Rodent cells having a disruption in a c9orf72 locus |
| HK1255346A1 (zh) | 2015-09-02 | 2019-08-16 | Regeneron Pharmaceuticals, Inc. | 前列腺癌的啮齿动物模型 |
| TWI752920B (zh) | 2015-10-12 | 2022-01-21 | 美商再生元醫藥公司 | 活化瘦素受體的抗原結合蛋白 |
| LT3376857T (lt) * | 2015-11-20 | 2021-06-25 | Regeneron Pharmaceuticals, Inc. | Gyvūnai, ne žmonės, turintys humanizuotą limfocitų aktyvavimo geną |
| ES2959326T3 (es) * | 2015-11-24 | 2024-02-23 | Glaxosmithkline Ip Dev Ltd | Líneas celulares estables para producción retroviral |
| DE102016122317A1 (de) * | 2015-11-24 | 2017-05-24 | Glaxosmithkline Intellectual Property Development Limited | Transientes transfektionsverfahren für retrovirale produktion |
| US10813346B2 (en) | 2015-12-03 | 2020-10-27 | Trianni, Inc. | Enhanced immunoglobulin diversity |
| KR102482103B1 (ko) | 2016-01-13 | 2022-12-28 | 리제너론 파마슈티칼스 인코포레이티드 | 조작된 중쇄 다양성 영역을 갖는 설치류 |
| US20170218398A1 (en) * | 2016-01-30 | 2017-08-03 | Markus Alexander Brown | Method to selectively target cancerous cells for genetic manipulation |
| US11053288B2 (en) | 2016-02-04 | 2021-07-06 | Trianni, Inc. | Enhanced production of immunoglobulins |
| CA3012693C (en) | 2016-02-04 | 2022-08-23 | Regeneron Pharmaceuticals, Inc. | Non-human animals having an engineered angptl8 gene |
| JP6765433B2 (ja) | 2016-02-12 | 2020-10-07 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | 異常な核型の検出のための方法 |
| AU2017221425A1 (en) | 2016-02-16 | 2018-08-23 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a mutant kynureninase gene |
| CN109068621B (zh) | 2016-02-29 | 2021-07-20 | 再生元制药公司 | 具有人源化的tmprss基因的啮齿类动物 |
| EP3437001A1 (en) | 2016-03-29 | 2019-02-06 | Regeneron Pharmaceuticals, Inc. | Genetic variant-phenotype analysis system and methods of use |
| AU2017268458B2 (en) | 2016-05-20 | 2022-07-21 | Regeneron Pharmaceuticals, Inc. | Methods for breaking immunological tolerance using multiple guide RNAS |
| EP3462853B1 (en) | 2016-06-03 | 2023-03-01 | Regeneron Pharmaceuticals, Inc. | Rodents expressing exogenous terminal deoxynucleotidyltransferase |
| KR20240113990A (ko) | 2016-06-27 | 2024-07-23 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 암 치료 조합 |
| WO2018001241A1 (zh) | 2016-06-28 | 2018-01-04 | 北京百奥赛图基因生物技术有限公司 | 一种pd-1基因修饰人源化动物模型的构建方法及其应用 |
| CN109803530A (zh) | 2016-07-29 | 2019-05-24 | 瑞泽恩制药公司 | 包含引起c-截短的原纤维蛋白-1表达的突变的小鼠 |
| KR102294755B1 (ko) | 2016-09-30 | 2021-08-31 | 리제너론 파마슈티칼스 인코포레이티드 | C9orf72 유전자좌에서 헥사뉴클레오티드 반복 확장을 갖는 비인간 동물 |
| PL3766343T3 (pl) | 2016-11-04 | 2022-09-26 | Regeneron Pharmaceuticals, Inc. | Zwierzęta inne niż człowiek posiadające zmodyfikowany sposobami inżynierii locus łańcucha lekkiego lambda immunoglobuliny |
| CN110662421B (zh) | 2017-01-19 | 2023-03-24 | 欧莫诺艾比公司 | 来自具有多个重链免疫球蛋白基因座的转基因啮齿类动物的人抗体 |
| AU2018224227A1 (en) | 2017-02-27 | 2019-08-29 | Regeneron Pharmaceuticals, Inc. | Non-human animal models of Retinoschisis |
| ES3033963T3 (en) | 2017-07-31 | 2025-08-11 | Regeneron Pharma | Method of testing the ability of a crispr/cas9 nuclease to modify a target genomic locus in vivo, by making use of a cas-transgenic mouse or rat which comprises a cas9 expression cassette in its genome |
| US11021719B2 (en) | 2017-07-31 | 2021-06-01 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for assessing CRISPER/Cas-mediated disruption or excision and CRISPR/Cas-induced recombination with an exogenous donor nucleic acid in vivo |
| KR102696334B1 (ko) | 2017-09-29 | 2024-08-21 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화 C1q 복합체를 발현하는 비인간 동물 |
| WO2019067875A1 (en) | 2017-09-29 | 2019-04-04 | Regeneron Pharmaceuticals, Inc. | NON-HUMAN ANIMALS COMPRISING A HUMANIZED TTR LOCUS AND METHODS OF USE |
| WO2019072241A1 (en) | 2017-10-13 | 2019-04-18 | Beijing Biocytogen Co., Ltd | NON-HUMAN ANIMAL GENETICALLY MODIFIED WITH PD-1 HUMAN OR CHIMERIC |
| CN109666701B (zh) * | 2017-10-13 | 2021-08-24 | 百奥赛图(北京)医药科技股份有限公司 | 一种pd-1基因修饰人源化动物模型的构建方法及其应用 |
| AU2018375796B2 (en) | 2017-11-30 | 2024-11-21 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized TRKB locus |
| PT3720279T (pt) | 2017-12-05 | 2022-10-06 | Regeneron Pharma | Ratinhos tendo uma cadeia leve lambda de imunoglobulina manipulada e seus usos |
| WO2019183123A1 (en) | 2018-03-19 | 2019-09-26 | Regeneron Pharmaceuticals, Inc. | Transcription modulation in animals using crispr/cas systems |
| AU2019242586B2 (en) | 2018-03-26 | 2025-09-11 | Regeneron Pharmaceuticals, Inc. | Humanized rodents for testing therapeutic agents |
| HRP20250986T1 (hr) | 2018-04-06 | 2025-10-24 | Regeneron Pharmaceuticals, Inc. | Antitijelo agonista leptinskog receptora za upotrebu u povećanju koštane mase kod osobe koja pati od metaboličke disfunkcije ili hipoleptinemije |
| JP2021525927A (ja) | 2018-06-01 | 2021-09-27 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドRegeneron Pharmaceuticals, Inc. | スパースベクトルベースのマトリクス変換のための方法およびシステム |
| IL318469A (en) | 2018-06-14 | 2025-03-01 | Regeneron Pharma | Non-human animals capable of reorganizing transgenic DH-DH, and their uses |
| PL3823443T3 (pl) | 2018-07-16 | 2024-09-23 | Regeneron Pharmaceuticals, Inc. | Modele gryzoni z chorobą ditra i ich zastosowania |
| CN109504708A (zh) * | 2018-12-03 | 2019-03-22 | 江苏集萃药康生物科技有限公司 | 一种筛选标记自我删除的基因打靶载体及方法 |
| CN113423831B (zh) | 2018-12-20 | 2023-03-10 | 瑞泽恩制药公司 | 核酸酶介导的重复扩增 |
| WO2020152607A1 (en) | 2019-01-22 | 2020-07-30 | St. Jude Children's Research Hospital | Modulation of lc3-associated endocytosis pathway and genetically modified non-human animals as a model of neuroinflammation and neurodegeneration |
| EP3927832A4 (en) * | 2019-02-18 | 2022-11-30 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | GENETICALLY MODIFIED NON-HUMAN ANIMALS WITH HUMANIZED IMMUNOGLOBULIN LOCUS |
| AU2020226865A1 (en) | 2019-02-22 | 2021-07-29 | Regeneron Pharmaceuticals, Inc. | Rodents having genetically modified sodium channels and methods of use thereof |
| IL286905B2 (en) | 2019-04-04 | 2024-06-01 | Regeneron Pharma | Non-human animals containing the human coagulation factor 12 locus |
| CN113795588B (zh) | 2019-04-04 | 2025-02-25 | 瑞泽恩制药公司 | 用于在靶向性载体中无瘢痕引入靶向修饰的方法 |
| US11136353B2 (en) | 2019-04-15 | 2021-10-05 | Qwixel Therapeutics Llc | Fusion protein composition(s) comprising masked type I interferons (IFNA and IFNB) for use in the treatment of cancer and methods thereof |
| WO2020247452A1 (en) | 2019-06-04 | 2020-12-10 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized ttr locus with a beta-slip mutation and methods of use |
| CA3136478A1 (en) | 2019-06-05 | 2020-12-10 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a limited lambda light chain repertoire expressed from the kappa locus and uses thereof |
| SG11202111256XA (en) | 2019-06-07 | 2021-11-29 | Regeneron Pharma | Non-human animals comprising a humanized albumin locus |
| WO2020264339A1 (en) | 2019-06-27 | 2020-12-30 | Regeneron Pharmaceuticals, Inc. | Modeling tdp-43 proteinopathy |
| CN114423785B (zh) | 2019-07-01 | 2025-04-22 | 通尼克斯制药有限公司 | 抗-cd154抗体及其用途 |
| US20240058466A1 (en) | 2019-10-04 | 2024-02-22 | TAE Life Sciences | Antibody Compositions Comprising Fc Mutations and Site-Specific Conjugation Properties For Use In Treating Cancer, Immunological Disorders, and Methods Thereof |
| WO2021108363A1 (en) | 2019-11-25 | 2021-06-03 | Regeneron Pharmaceuticals, Inc. | Crispr/cas-mediated upregulation of humanized ttr allele |
| US12250931B2 (en) | 2020-01-28 | 2025-03-18 | Regeneron Pharmaceuticals, Inc. | Genetically modified mouse with a humanized PNPLA3 gene and methods of use |
| US20230081547A1 (en) | 2020-02-07 | 2023-03-16 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized klkb1 locus and methods of use |
| EP4125348A1 (en) | 2020-03-23 | 2023-02-08 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized ttr locus comprising a v30m mutation and methods of use |
| EP4138550A1 (en) | 2020-04-21 | 2023-03-01 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized cxcl13 gene |
| CN115667532A (zh) | 2020-06-02 | 2023-01-31 | 百奥赛图(北京)医药科技股份有限公司 | 具有共有轻链免疫球蛋白基因座的经遗传修饰的非人动物 |
| RU2751237C1 (ru) * | 2020-06-10 | 2021-07-12 | Регенерон Фармасьютикалс, Инк. | Способы и композиции для направленной модификации генома |
| JP2023541216A (ja) | 2020-06-25 | 2023-09-29 | ヒューマブ カンパニー リミテッド | ヘテロ接合型トランスジェニック動物 |
| IL301137A (en) | 2020-09-11 | 2023-05-01 | Regeneron Pharma | Identification and production of antigen-specific antibodies |
| US12082566B2 (en) | 2020-10-01 | 2024-09-10 | Regeneron Pharmaceuticals, Inc. | Rodent animals expressing human CR1 |
| US12012441B2 (en) | 2020-10-26 | 2024-06-18 | Neptune Biosciences Llc | Engineered human IL-21 cytokines and methods for using the same |
| CN116848254A (zh) | 2020-12-16 | 2023-10-03 | 瑞泽恩制药公司 | 表达人源化Fcα受体的小鼠 |
| WO2022140221A1 (en) | 2020-12-21 | 2022-06-30 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized tslp gene, a humanized tslp receptor gene, and/or a humanized il7ra gene |
| EP4559939A3 (en) | 2020-12-23 | 2025-09-24 | Regeneron Pharmaceuticals, Inc. | Nucleic acids encoding anchor modified antibodies and uses therof |
| AU2022205313A1 (en) | 2021-01-06 | 2023-07-20 | Tonix Pharma Limited | Methods of inducing immune tolerance with modified anti-cd154 antibodies |
| AU2022249328A1 (en) | 2021-03-31 | 2023-09-21 | Regeneron Pharmaceuticals, Inc. | Genetically modified mice comprising humanized cellular immune system components with improved diversity of tcrβ repertoire |
| US20240199725A1 (en) | 2021-04-16 | 2024-06-20 | Korea University Research And Business Foundation | Human antibody targeting covid-19 virus |
| CA3221878A1 (en) | 2021-06-18 | 2022-12-22 | David Stover | Fusion protein composition(s) comprising masked type i interferons (ifna and ifnb) for use in the treatment of cancer and methods thereof |
| EP4423271A2 (en) | 2021-10-28 | 2024-09-04 | Regeneron Pharmaceuticals, Inc. | Crispr/cas-related methods and compositions for knocking out c5 |
| IL312971A (en) | 2021-12-08 | 2024-07-01 | Regeneron Pharma | Mutant myocilin disease model and uses thereof |
| WO2023122506A1 (en) | 2021-12-20 | 2023-06-29 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising humanized ace2 and tmprss loci |
| EP4475671A1 (en) | 2022-02-07 | 2024-12-18 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for defining optimal treatment timeframes in lysosomal disease |
| KR20240144138A (ko) | 2022-02-11 | 2024-10-02 | 리제너론 파마슈티칼스 인코포레이티드 | 4r 타우 표적화제를 스크리닝하기 위한 조성물 및 방법 |
| WO2023212560A1 (en) | 2022-04-26 | 2023-11-02 | Regeneron Pharmaceuticals, Inc. | A rodent model of fibrodysplasia ossificans progressiva |
| EP4531554A1 (en) | 2022-05-31 | 2025-04-09 | Regeneron Pharmaceuticals, Inc. | Animal model of tdp-43 proteinopathy |
| WO2023235725A2 (en) | 2022-05-31 | 2023-12-07 | Regeneron Pharmaceuticals, Inc. | Crispr-based therapeutics for c9orf72 repeat expansion disease |
| US20230417899A1 (en) | 2022-06-27 | 2023-12-28 | Oshkosh Corporation | Position tracking for a lift device |
| CA3260622A1 (en) | 2022-07-19 | 2024-01-25 | Regeneron Pharmaceuticals, Inc. | GENETICALLY MODIFIED ANIMAL MODEL AND ITS USE TO MODEL THE HUMAN IMMUNE SYSTEM |
| KR20250077529A (ko) | 2022-09-22 | 2025-05-30 | 리제너론 파아마슈티컬스, 인크. | 인간 세포 면역계의 성분을 발현하는, 유전자적으로 변형된 마우스 |
| US20240224964A9 (en) | 2022-09-29 | 2024-07-11 | Regeneron Pharmaceuticals, Inc. | Correction of hepatosteatosis in humanized liver animals through restoration of il6/il6r/gp130 signaling in human hepatocytes |
| CN120603491A (zh) | 2023-02-01 | 2025-09-05 | 瑞泽恩制药公司 | 包含修饰的klhdc7b基因座的动物 |
| WO2024258743A1 (en) | 2023-06-13 | 2024-12-19 | Adcentrx Therapeutics, Inc. | Methods and compositions related to antibodies and antibody drug conjugates (adcs) that bind nectin-4 proteins |
| US20240415103A1 (en) | 2023-06-16 | 2024-12-19 | Regeneron Pharmaceuticals, Inc. | Vectors, genetically modified cells, and genetically modified non-human animals comprising the same |
| WO2025122669A1 (en) | 2023-12-05 | 2025-06-12 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized complement factor b gene |
| US20250255282A1 (en) | 2024-02-08 | 2025-08-14 | Regeneron Pharmaceuticals, Inc. | Vectors, genetically modified cells, and genetically modified non-human animals comprising the same |
| WO2025212991A1 (en) | 2024-04-05 | 2025-10-09 | Regeneron Pharmaceuticals, Inc. | Rodent models of disease |
| WO2025235388A1 (en) | 2024-05-06 | 2025-11-13 | Regeneron Pharmaceuticals, Inc. | Transgene genomic identification by nuclease-mediated long read sequencing |
| WO2025250495A1 (en) | 2024-05-28 | 2025-12-04 | Regeneron Pharmaceuticals, Inc. | Acceleration of human hepatocyte engraftment in humanized liver animals by supplementing paracrine ligands or agonists that activate human liver regeneration signals |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5770429A (en) * | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| AU2515992A (en) | 1991-08-20 | 1993-03-16 | Genpharm International, Inc. | Gene targeting in animal cells using isogenic dna constructs |
| ATE381614T1 (de) * | 1992-07-24 | 2008-01-15 | Amgen Fremont Inc | Bildung von xenogenen antikörpern |
| DE4228162C1 (de) * | 1992-08-25 | 1994-01-13 | Rajewsky Klaus Dr | Verfahren zum Ersetzen homologer Genabschnitte aus Säugern in der Keimbahn von nicht-menschlichen Säugern |
| US5436149A (en) | 1993-02-19 | 1995-07-25 | Barnes; Wayne M. | Thermostable DNA polymerase with enhanced thermostability and enhanced length and efficiency of primer extension |
| CA2161351C (en) * | 1993-04-26 | 2010-12-21 | Nils Lonberg | Transgenic non-human animals capable of producing heterologous antibodies |
| CA2362098C (en) * | 1999-02-05 | 2011-10-11 | Jens-Ulrich Bulow | Human polyclonal antibodies from genetically engineered animals |
| US6586251B2 (en) * | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
-
2000
- 2000-12-07 US US09/732,234 patent/US6586251B2/en not_active Expired - Lifetime
-
2001
- 2001-10-31 AT AT01992495T patent/ATE332388T1/de not_active IP Right Cessation
- 2001-10-31 JP JP2002539535A patent/JP5339566B2/ja not_active Expired - Lifetime
- 2001-10-31 PL PL361927A patent/PL204759B1/pl unknown
- 2001-10-31 CZ CZ2003-1197A patent/CZ304856B6/cs not_active IP Right Cessation
- 2001-10-31 HU HU0301575A patent/HU227639B1/hu unknown
- 2001-10-31 AU AU2004802A patent/AU2004802A/xx active Pending
- 2001-10-31 NZ NZ525511A patent/NZ525511A/en not_active IP Right Cessation
- 2001-10-31 RU RU2003116125/13A patent/RU2290441C2/ru active
- 2001-10-31 AU AU2002220048A patent/AU2002220048B2/en not_active Expired
- 2001-10-31 BR BRPI0115096A patent/BRPI0115096B1/pt active IP Right Grant
- 2001-10-31 KR KR1020037005885A patent/KR100833136B1/ko not_active Expired - Lifetime
- 2001-10-31 MX MXPA03003797A patent/MXPA03003797A/es active IP Right Grant
- 2001-10-31 EP EP01992495A patent/EP1399575B1/en not_active Expired - Lifetime
- 2001-10-31 DE DE60121372T patent/DE60121372T2/de not_active Expired - Lifetime
- 2001-10-31 WO PCT/US2001/045375 patent/WO2002036789A2/en not_active Ceased
- 2001-10-31 CA CA2426398A patent/CA2426398C/en not_active Expired - Lifetime
- 2001-10-31 CN CNB018216609A patent/CN100497642C/zh not_active Expired - Lifetime
-
2003
- 2003-04-28 NO NO20031897A patent/NO332300B1/no not_active IP Right Cessation
-
2010
- 2010-06-15 JP JP2010136321A patent/JP2010220628A/ja active Pending
-
2013
- 2013-05-23 JP JP2013108631A patent/JP5892975B2/ja not_active Expired - Lifetime
- 2013-11-29 JP JP2013247817A patent/JP5945263B2/ja not_active Expired - Lifetime
-
2014
- 2014-12-26 JP JP2014265082A patent/JP2015062432A/ja not_active Withdrawn
-
2017
- 2017-02-14 JP JP2017024803A patent/JP6486979B2/ja not_active Expired - Lifetime
- 2017-02-14 JP JP2017024802A patent/JP2017123855A/ja not_active Withdrawn
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60121372T2 (de) | Methoden zur modifikation eukaryotischer zellen | |
| US10344299B2 (en) | Compositions and methods for modifying cells | |
| AU2002220048A1 (en) | Methods of modifying eukaryotic cells | |
| JP5692863B2 (ja) | 真核生物細胞を改変する方法 | |
| EP1214440B1 (de) | Sequenz-spezifische dna-rekombination in eukaryotischen zellen | |
| HK1059802B (en) | Methods of modifying eukaryotic cells | |
| IL155580A (en) | Ex vivo method for modifying endogenous gene or chromosomal locus in eukaryotic cells | |
| HK40015541A (en) | Transgenic mouse which produces hybrid antibodies containing human variable regions and mouse constant regions |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |