AU2012222144B2 - Genetically modified animals and methods for making the same - Google Patents
Genetically modified animals and methods for making the same Download PDFInfo
- Publication number
- AU2012222144B2 AU2012222144B2 AU2012222144A AU2012222144A AU2012222144B2 AU 2012222144 B2 AU2012222144 B2 AU 2012222144B2 AU 2012222144 A AU2012222144 A AU 2012222144A AU 2012222144 A AU2012222144 A AU 2012222144A AU 2012222144 B2 AU2012222144 B2 AU 2012222144B2
- Authority
- AU
- Australia
- Prior art keywords
- cell
- talen
- embryo
- bovine
- allele
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 122
- 241001465754 Metazoa Species 0.000 title claims abstract description 97
- 210000004027 cell Anatomy 0.000 claims abstract description 214
- 238000010459 TALEN Methods 0.000 claims abstract description 169
- 108010043645 Transcription Activator-Like Effector Nucleases Proteins 0.000 claims abstract description 168
- 244000144972 livestock Species 0.000 claims abstract description 60
- 210000000130 stem cell Anatomy 0.000 claims abstract description 15
- 150000007523 nucleic acids Chemical class 0.000 claims description 123
- 102000039446 nucleic acids Human genes 0.000 claims description 99
- 108020004707 nucleic acids Proteins 0.000 claims description 99
- 108700028369 Alleles Proteins 0.000 claims description 90
- 108090000623 proteins and genes Proteins 0.000 claims description 87
- 210000001161 mammalian embryo Anatomy 0.000 claims description 80
- 239000013598 vector Substances 0.000 claims description 66
- 241000283690 Bos taurus Species 0.000 claims description 65
- 238000012217 deletion Methods 0.000 claims description 61
- 230000037430 deletion Effects 0.000 claims description 61
- 238000012239 gene modification Methods 0.000 claims description 61
- 230000005017 genetic modification Effects 0.000 claims description 56
- 235000013617 genetically modified food Nutrition 0.000 claims description 56
- 102000018120 Recombinases Human genes 0.000 claims description 51
- 108010091086 Recombinases Proteins 0.000 claims description 51
- 230000004048 modification Effects 0.000 claims description 49
- 238000012986 modification Methods 0.000 claims description 49
- 241000282898 Sus scrofa Species 0.000 claims description 46
- 101710163270 Nuclease Proteins 0.000 claims description 32
- 239000003550 marker Substances 0.000 claims description 31
- 108020004999 messenger RNA Proteins 0.000 claims description 31
- 238000003780 insertion Methods 0.000 claims description 26
- 230000037431 insertion Effects 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 23
- 239000013612 plasmid Substances 0.000 claims description 20
- 108700008625 Reporter Genes Proteins 0.000 claims description 16
- 238000010367 cloning Methods 0.000 claims description 15
- 210000002459 blastocyst Anatomy 0.000 claims description 14
- 238000000338 in vitro Methods 0.000 claims description 14
- 238000012546 transfer Methods 0.000 claims description 13
- 230000002068 genetic effect Effects 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 238000010374 somatic cell nuclear transfer Methods 0.000 claims description 8
- 108010056852 Myostatin Proteins 0.000 claims description 7
- 238000009395 breeding Methods 0.000 claims description 6
- 230000001488 breeding effect Effects 0.000 claims description 6
- 210000004602 germ cell Anatomy 0.000 claims description 6
- 210000004748 cultured cell Anatomy 0.000 claims description 5
- 108010077544 Chromatin Proteins 0.000 claims description 4
- 210000003483 chromatin Anatomy 0.000 claims description 4
- 210000001082 somatic cell Anatomy 0.000 claims description 4
- 239000013611 chromosomal DNA Substances 0.000 claims description 2
- 102000004472 Myostatin Human genes 0.000 claims 2
- 210000002257 embryonic structure Anatomy 0.000 abstract description 43
- 239000000203 mixture Substances 0.000 abstract description 14
- 108020004414 DNA Proteins 0.000 description 85
- 230000014509 gene expression Effects 0.000 description 39
- 230000000694 effects Effects 0.000 description 38
- 102000001218 Rec A Recombinases Human genes 0.000 description 36
- 108010055016 Rec A Recombinases Proteins 0.000 description 36
- 102000004169 proteins and genes Human genes 0.000 description 35
- 235000018102 proteins Nutrition 0.000 description 34
- 241001493546 Suina Species 0.000 description 27
- 230000035772 mutation Effects 0.000 description 27
- 238000003752 polymerase chain reaction Methods 0.000 description 26
- 108091028043 Nucleic acid sequence Proteins 0.000 description 24
- 210000002950 fibroblast Anatomy 0.000 description 21
- 230000027455 binding Effects 0.000 description 20
- 230000009261 transgenic effect Effects 0.000 description 19
- 238000003556 assay Methods 0.000 description 18
- 230000006798 recombination Effects 0.000 description 18
- 230000001404 mediated effect Effects 0.000 description 17
- 210000000287 oocyte Anatomy 0.000 description 17
- 238000005215 recombination Methods 0.000 description 17
- 210000000349 chromosome Anatomy 0.000 description 16
- 108010042407 Endonucleases Proteins 0.000 description 15
- 239000013615 primer Substances 0.000 description 15
- 230000008569 process Effects 0.000 description 15
- 229920001184 polypeptide Polymers 0.000 description 14
- 102000004196 processed proteins & peptides Human genes 0.000 description 14
- 108090000765 processed proteins & peptides Proteins 0.000 description 14
- 108010020764 Transposases Proteins 0.000 description 13
- 102000008579 Transposases Human genes 0.000 description 13
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 13
- 239000002773 nucleotide Substances 0.000 description 13
- 125000003729 nucleotide group Chemical group 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 13
- 238000002347 injection Methods 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- 230000008439 repair process Effects 0.000 description 12
- 125000006850 spacer group Chemical group 0.000 description 12
- 102000053602 DNA Human genes 0.000 description 11
- 230000006801 homologous recombination Effects 0.000 description 11
- 238000002744 homologous recombination Methods 0.000 description 11
- 230000001105 regulatory effect Effects 0.000 description 11
- 238000013518 transcription Methods 0.000 description 11
- 230000035897 transcription Effects 0.000 description 11
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 description 10
- 238000003776 cleavage reaction Methods 0.000 description 10
- 230000005782 double-strand break Effects 0.000 description 10
- 230000006780 non-homologous end joining Effects 0.000 description 10
- 238000012163 sequencing technique Methods 0.000 description 10
- 238000001890 transfection Methods 0.000 description 10
- 102000004533 Endonucleases Human genes 0.000 description 9
- 102100039939 Growth/differentiation factor 8 Human genes 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 239000000178 monomer Substances 0.000 description 9
- 230000007017 scission Effects 0.000 description 9
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 8
- 101100300807 Drosophila melanogaster spn-A gene Proteins 0.000 description 8
- 241000196324 Embryophyta Species 0.000 description 8
- 108700019146 Transgenes Proteins 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 235000013601 eggs Nutrition 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 230000004927 fusion Effects 0.000 description 8
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 108010051219 Cre recombinase Proteins 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 241000282414 Homo sapiens Species 0.000 description 7
- 102000011931 Nucleoproteins Human genes 0.000 description 7
- 108010061100 Nucleoproteins Proteins 0.000 description 7
- -1 RAD51 Proteins 0.000 description 7
- 241000282887 Suidae Species 0.000 description 7
- 229940088598 enzyme Drugs 0.000 description 7
- 102100024108 Dystrophin Human genes 0.000 description 6
- 102100031780 Endonuclease Human genes 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 238000012761 co-transfection Methods 0.000 description 6
- 238000005520 cutting process Methods 0.000 description 6
- 238000010363 gene targeting Methods 0.000 description 6
- 238000000520 microinjection Methods 0.000 description 6
- 239000004055 small Interfering RNA Substances 0.000 description 6
- 241000283707 Capra Species 0.000 description 5
- 206010061764 Chromosomal deletion Diseases 0.000 description 5
- 230000033616 DNA repair Effects 0.000 description 5
- 241000588724 Escherichia coli Species 0.000 description 5
- 108091034117 Oligonucleotide Proteins 0.000 description 5
- 240000007019 Oxalis corniculata Species 0.000 description 5
- 102000002490 Rad51 Recombinase Human genes 0.000 description 5
- 102000006601 Thymidine Kinase Human genes 0.000 description 5
- 108020004440 Thymidine kinase Proteins 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 210000001671 embryonic stem cell Anatomy 0.000 description 5
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 5
- BRZYSWJRSDMWLG-CAXSIQPQSA-N geneticin Natural products O1C[C@@](O)(C)[C@H](NC)[C@@H](O)[C@H]1O[C@@H]1[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](C(C)O)O2)N)[C@@H](N)C[C@H]1N BRZYSWJRSDMWLG-CAXSIQPQSA-N 0.000 description 5
- 238000010362 genome editing Methods 0.000 description 5
- 210000005260 human cell Anatomy 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 239000012212 insulator Substances 0.000 description 5
- 102000054765 polymorphisms of proteins Human genes 0.000 description 5
- 102000040430 polynucleotide Human genes 0.000 description 5
- 108091033319 polynucleotide Proteins 0.000 description 5
- 239000002157 polynucleotide Substances 0.000 description 5
- 230000035935 pregnancy Effects 0.000 description 5
- 230000000392 somatic effect Effects 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 4
- 241000251468 Actinopterygii Species 0.000 description 4
- 102000055025 Adenosine deaminases Human genes 0.000 description 4
- 108091093088 Amplicon Proteins 0.000 description 4
- 230000004568 DNA-binding Effects 0.000 description 4
- 241000252212 Danio rerio Species 0.000 description 4
- UPEZCKBFRMILAV-JNEQICEOSA-N Ecdysone Natural products O=C1[C@H]2[C@@](C)([C@@H]3C([C@@]4(O)[C@@](C)([C@H]([C@H]([C@@H](O)CCC(O)(C)C)C)CC4)CC3)=C1)C[C@H](O)[C@H](O)C2 UPEZCKBFRMILAV-JNEQICEOSA-N 0.000 description 4
- 108700024394 Exon Proteins 0.000 description 4
- 101000886562 Homo sapiens Growth/differentiation factor 8 Proteins 0.000 description 4
- 108010025815 Kanamycin Kinase Proteins 0.000 description 4
- 108010077850 Nuclear Localization Signals Proteins 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 241001494479 Pecora Species 0.000 description 4
- 108010068097 Rad51 Recombinase Proteins 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- 101100264226 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) XRN1 gene Proteins 0.000 description 4
- 108091027967 Small hairpin RNA Proteins 0.000 description 4
- 108010022394 Threonine synthase Proteins 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- UPEZCKBFRMILAV-UHFFFAOYSA-N alpha-Ecdysone Natural products C1C(O)C(O)CC2(C)C(CCC3(C(C(C(O)CCC(C)(C)O)C)CCC33O)C)C3=CC(=O)C21 UPEZCKBFRMILAV-UHFFFAOYSA-N 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 230000001413 cellular effect Effects 0.000 description 4
- 230000000295 complement effect Effects 0.000 description 4
- 230000001276 controlling effect Effects 0.000 description 4
- 102000004419 dihydrofolate reductase Human genes 0.000 description 4
- UPEZCKBFRMILAV-JMZLNJERSA-N ecdysone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@@H]([C@H](O)CCC(C)(C)O)C)CC[C@]33O)C)C3=CC(=O)[C@@H]21 UPEZCKBFRMILAV-JMZLNJERSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 210000003101 oviduct Anatomy 0.000 description 4
- 229950010131 puromycin Drugs 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 102000011022 Chorionic Gonadotropin Human genes 0.000 description 3
- 108010062540 Chorionic Gonadotropin Proteins 0.000 description 3
- 208000016718 Chromosome Inversion Diseases 0.000 description 3
- 241000701022 Cytomegalovirus Species 0.000 description 3
- 230000007018 DNA scission Effects 0.000 description 3
- 108091029865 Exogenous DNA Proteins 0.000 description 3
- 108010014594 Heterogeneous Nuclear Ribonucleoprotein A1 Proteins 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 108020004682 Single-Stranded DNA Proteins 0.000 description 3
- 108020004459 Small interfering RNA Proteins 0.000 description 3
- 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 3
- 230000004913 activation Effects 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000000692 anti-sense effect Effects 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 230000002759 chromosomal effect Effects 0.000 description 3
- 210000000805 cytoplasm Anatomy 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000006471 dimerization reaction Methods 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 230000001605 fetal effect Effects 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 238000010353 genetic engineering Methods 0.000 description 3
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 3
- 238000002513 implantation Methods 0.000 description 3
- 238000010348 incorporation Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 230000021121 meiosis Effects 0.000 description 3
- 230000002018 overexpression Effects 0.000 description 3
- 108020001580 protein domains Proteins 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 101150079601 recA gene Proteins 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 230000009870 specific binding Effects 0.000 description 3
- 230000002103 transcriptional effect Effects 0.000 description 3
- 230000017105 transposition Effects 0.000 description 3
- 241001430294 unidentified retrovirus Species 0.000 description 3
- 239000013603 viral vector Substances 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- ZXXTYLFVENEGIP-UHFFFAOYSA-N 2-amino-3,7-dihydropurin-6-one;3,7-dihydropurine-2,6-dione Chemical compound O=C1NC(N)=NC2=C1NC=N2.O=C1NC(=O)NC2=C1NC=N2 ZXXTYLFVENEGIP-UHFFFAOYSA-N 0.000 description 2
- 102100036962 5'-3' exoribonuclease 1 Human genes 0.000 description 2
- 208000007407 African swine fever Diseases 0.000 description 2
- 101100228731 Bos taurus MSTN gene Proteins 0.000 description 2
- 108091060290 Chromatid Proteins 0.000 description 2
- 108010063593 DNA modification methylase SssI Proteins 0.000 description 2
- 102100022928 DNA repair protein RAD51 homolog 1 Human genes 0.000 description 2
- 108010014303 DNA-directed DNA polymerase Proteins 0.000 description 2
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 2
- 101100332287 Dictyostelium discoideum dst2 gene Proteins 0.000 description 2
- 102100032049 E3 ubiquitin-protein ligase LRSAM1 Human genes 0.000 description 2
- 108060002716 Exonuclease Proteins 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 101000834253 Gallus gallus Actin, cytoplasmic 1 Proteins 0.000 description 2
- 102000005720 Glutathione transferase Human genes 0.000 description 2
- 108010070675 Glutathione transferase Proteins 0.000 description 2
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 2
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 2
- 108091027305 Heteroduplex Proteins 0.000 description 2
- 108010056307 Hin recombinase Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000804879 Homo sapiens 5'-3' exoribonuclease 1 Proteins 0.000 description 2
- 101000620735 Homo sapiens DNA repair protein RAD51 homolog 1 Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- 102100034343 Integrase Human genes 0.000 description 2
- 108010061833 Integrases Proteins 0.000 description 2
- 101150013552 LDLR gene Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001024304 Mino Species 0.000 description 2
- 206010068052 Mosaicism Diseases 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 244000061176 Nicotiana tabacum Species 0.000 description 2
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 2
- 238000012408 PCR amplification Methods 0.000 description 2
- 238000002944 PCR assay Methods 0.000 description 2
- 108010076504 Protein Sorting Signals Proteins 0.000 description 2
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 2
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 2
- 101001059240 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Site-specific recombinase Flp Proteins 0.000 description 2
- 241000607142 Salmonella Species 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 241000700584 Simplexvirus Species 0.000 description 2
- 238000002105 Southern blotting Methods 0.000 description 2
- 241001661355 Synapsis Species 0.000 description 2
- 208000012827 T-B+ severe combined immunodeficiency due to gamma chain deficiency Diseases 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 101710183280 Topoisomerase Proteins 0.000 description 2
- 208000023940 X-Linked Combined Immunodeficiency disease Diseases 0.000 description 2
- 201000007146 X-linked severe combined immunodeficiency Diseases 0.000 description 2
- 210000004504 adult stem cell Anatomy 0.000 description 2
- 238000007844 allele-specific PCR Methods 0.000 description 2
- 102000006646 aminoglycoside phosphotransferase Human genes 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 210000004102 animal cell Anatomy 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 108091092356 cellular DNA Proteins 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 235000013330 chicken meat Nutrition 0.000 description 2
- 210000004756 chromatid Anatomy 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 210000001771 cumulus cell Anatomy 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000000326 densiometry Methods 0.000 description 2
- 230000001066 destructive effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- 238000002224 dissection Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000004520 electroporation Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 102000013165 exonuclease Human genes 0.000 description 2
- 230000004720 fertilization Effects 0.000 description 2
- 210000001733 follicular fluid Anatomy 0.000 description 2
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 2
- 229960002963 ganciclovir Drugs 0.000 description 2
- 230000009368 gene silencing by RNA Effects 0.000 description 2
- 238000013412 genome amplification Methods 0.000 description 2
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 239000005090 green fluorescent protein Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000009027 insemination Effects 0.000 description 2
- 230000009545 invasion Effects 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 238000002703 mutagenesis Methods 0.000 description 2
- 231100000350 mutagenesis Toxicity 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 238000011536 re-plating Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000012340 reverse transcriptase PCR Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 238000005204 segregation Methods 0.000 description 2
- 231100000188 sister chromatid exchange Toxicity 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 108700020534 tetracycline resistance-encoding transposon repressor Proteins 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- 108091006106 transcriptional activators Proteins 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 230000024540 transposon integration Effects 0.000 description 2
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 1
- MXHRCPNRJAMMIM-SHYZEUOFSA-N 2'-deoxyuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-SHYZEUOFSA-N 0.000 description 1
- CKTSBUTUHBMZGZ-SHYZEUOFSA-N 2'‐deoxycytidine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 CKTSBUTUHBMZGZ-SHYZEUOFSA-N 0.000 description 1
- 101150090724 3 gene Proteins 0.000 description 1
- LQGNCUXDDPRDJH-UHFFFAOYSA-N 3'-GMP Natural products C1C(O)C(O)CC2(C)C(C(O)CC3(C(C(C)(O)C(O)CCC(C)C)CCC33O)C)C3=CC(=O)C21 LQGNCUXDDPRDJH-UHFFFAOYSA-N 0.000 description 1
- OSJPPGNTCRNQQC-UWTATZPHSA-N 3-phospho-D-glyceric acid Chemical compound OC(=O)[C@H](O)COP(O)(O)=O OSJPPGNTCRNQQC-UWTATZPHSA-N 0.000 description 1
- LUCHPKXVUGJYGU-XLPZGREQSA-N 5-methyl-2'-deoxycytidine Chemical compound O=C1N=C(N)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 LUCHPKXVUGJYGU-XLPZGREQSA-N 0.000 description 1
- 101150039504 6 gene Proteins 0.000 description 1
- 108091006112 ATPases Proteins 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 241000589158 Agrobacterium Species 0.000 description 1
- 102100027211 Albumin Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 101000886576 Bos taurus Growth/differentiation factor 8 Proteins 0.000 description 1
- 241000282832 Camelidae Species 0.000 description 1
- 241000282994 Cervidae Species 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 239000003155 DNA primer Substances 0.000 description 1
- 102100033934 DNA repair protein RAD51 homolog 2 Human genes 0.000 description 1
- 102100027830 DNA repair protein XRCC2 Human genes 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 101710150441 DNA-invertase Proteins 0.000 description 1
- CKTSBUTUHBMZGZ-UHFFFAOYSA-N Deoxycytidine Natural products O=C1N=C(N)C=CN1C1OC(CO)C(O)C1 CKTSBUTUHBMZGZ-UHFFFAOYSA-N 0.000 description 1
- 241000702421 Dependoparvovirus Species 0.000 description 1
- 208000035240 Disease Resistance Diseases 0.000 description 1
- 241000255581 Drosophila <fruit fly, genus> Species 0.000 description 1
- 101100449429 Drosophila melanogaster Gr5a gene Proteins 0.000 description 1
- 102000001039 Dystrophin Human genes 0.000 description 1
- 108010069091 Dystrophin Proteins 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000701533 Escherichia virus T4 Species 0.000 description 1
- 108010046276 FLP recombinase Proteins 0.000 description 1
- 108010058643 Fungal Proteins Proteins 0.000 description 1
- 240000005702 Galium aparine Species 0.000 description 1
- 235000014820 Galium aparine Nutrition 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101100412102 Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd) rec2 gene Proteins 0.000 description 1
- 241000282824 Hippopotamidae Species 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 108091064358 Holliday junction Proteins 0.000 description 1
- 102000039011 Holliday junction Human genes 0.000 description 1
- 101000649306 Homo sapiens DNA repair protein XRCC2 Proteins 0.000 description 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 1
- 108010003272 Hyaluronate lyase Proteins 0.000 description 1
- 102000001974 Hyaluronidases Human genes 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 101710196632 LexA repressor Proteins 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 102000011965 Lipoprotein Receptors Human genes 0.000 description 1
- 108010061306 Lipoprotein Receptors Proteins 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 241000713869 Moloney murine leukemia virus Species 0.000 description 1
- LRJUYAVTHIEHAI-UHFFFAOYSA-N Muristeron A Natural products C1C(O)C(O)CC2(C)C(C(O)CC3(C(C(C)(O)C(O)CCC(C)C)CCC33O)C)C3=CC(=O)C21O LRJUYAVTHIEHAI-UHFFFAOYSA-N 0.000 description 1
- LRJUYAVTHIEHAI-LHBNDURVSA-N Muristerone Chemical compound C1[C@@H](O)[C@@H](O)C[C@]2(C)[C@@H]([C@H](O)C[C@@]3([C@@H]([C@@](C)(O)[C@H](O)CCC(C)C)CC[C@]33O)C)C3=CC(=O)[C@@]21O LRJUYAVTHIEHAI-LHBNDURVSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 238000000636 Northern blotting Methods 0.000 description 1
- 238000010222 PCR analysis Methods 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 241000269907 Pleuronectes platessa Species 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108700040121 Protein Methyltransferases Proteins 0.000 description 1
- 102000055027 Protein Methyltransferases Human genes 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 102000053062 Rad52 DNA Repair and Recombination Human genes 0.000 description 1
- 108700031762 Rad52 DNA Repair and Recombination Proteins 0.000 description 1
- 102000018780 Replication Protein A Human genes 0.000 description 1
- 108010027643 Replication Protein A Proteins 0.000 description 1
- 102000009661 Repressor Proteins Human genes 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- MEFKEPWMEQBLKI-AIRLBKTGSA-N S-adenosyl-L-methioninate Chemical compound O[C@@H]1[C@H](O)[C@@H](C[S+](CC[C@H](N)C([O-])=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 MEFKEPWMEQBLKI-AIRLBKTGSA-N 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 101001010097 Shigella phage SfV Bactoprenol-linked glucose translocase Proteins 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 241000255588 Tephritidae Species 0.000 description 1
- 241000589500 Thermus aquaticus Species 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108010064978 Type II Site-Specific Deoxyribonucleases Proteins 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 102000011856 Utrophin Human genes 0.000 description 1
- 108010075653 Utrophin Proteins 0.000 description 1
- 108010051583 Ventricular Myosins Proteins 0.000 description 1
- 210000001766 X chromosome Anatomy 0.000 description 1
- 210000002593 Y chromosome Anatomy 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 229960001570 ademetionine Drugs 0.000 description 1
- NLTUCYMLOPLUHL-KQYNXXCUSA-N adenosine 5'-[gamma-thio]triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=S)[C@@H](O)[C@H]1O NLTUCYMLOPLUHL-KQYNXXCUSA-N 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 238000003339 best practice Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 210000001109 blastomere Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000012411 cloning technique Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 101150036876 cre gene Proteins 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- SUYVUBYJARFZHO-RRKCRQDMSA-N dATP Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@H]1C[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-RRKCRQDMSA-N 0.000 description 1
- SUYVUBYJARFZHO-UHFFFAOYSA-N dATP Natural products C1=NC=2C(N)=NC=NC=2N1C1CC(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 SUYVUBYJARFZHO-UHFFFAOYSA-N 0.000 description 1
- MXHRCPNRJAMMIM-UHFFFAOYSA-N desoxyuridine Natural products C1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 MXHRCPNRJAMMIM-UHFFFAOYSA-N 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical group OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 1
- 230000012361 double-strand break repair Effects 0.000 description 1
- 230000034431 double-strand break repair via homologous recombination Effects 0.000 description 1
- 229960003722 doxycycline Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 108010057988 ecdysone receptor Proteins 0.000 description 1
- 230000005014 ectopic expression Effects 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- 239000013613 expression plasmid Substances 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 210000000604 fetal stem cell Anatomy 0.000 description 1
- 230000003325 follicular Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 230000037433 frameshift Effects 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 238000001476 gene delivery Methods 0.000 description 1
- 235000003869 genetically modified organism Nutrition 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 210000002503 granulosa cell Anatomy 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- 239000000710 homodimer Substances 0.000 description 1
- 229960002773 hyaluronidase Drugs 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006607 hypermethylation Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 210000004263 induced pluripotent stem cell Anatomy 0.000 description 1
- 239000002428 insect molting hormone Substances 0.000 description 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 238000009533 lab test Methods 0.000 description 1
- 238000007834 ligase chain reaction Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 210000004216 mammary stem cell Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 238000010449 nuclear transplantation Methods 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 108010083127 phage repressor proteins Proteins 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- SXADIBFZNXBEGI-UHFFFAOYSA-N phosphoramidous acid Chemical compound NP(O)O SXADIBFZNXBEGI-UHFFFAOYSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 210000004508 polar body Anatomy 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 235000020004 porter Nutrition 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000000270 postfertilization Effects 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 235000013594 poultry meat Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000011045 prefiltration Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 101150085542 relA gene Proteins 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 108091008146 restriction endonucleases Proteins 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000007480 sanger sequencing Methods 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 238000009612 semen analysis Methods 0.000 description 1
- 230000009758 senescence Effects 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000014639 sexual reproduction Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000035892 strand transfer Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 210000003371 toe Anatomy 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001052 transient 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
- 238000002604 ultrasonography Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 108700023967 zebrafish Rad52 Proteins 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- XOFLBQFBSOEHOG-UUOKFMHZSA-N γS-GTP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=S)[C@@H](O)[C@H]1O XOFLBQFBSOEHOG-UUOKFMHZSA-N 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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
- A61D19/00—Instruments or methods for reproduction or fertilisation
- A61D19/04—Instruments or methods for reproduction or fertilisation for embryo 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
- 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
-
- 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
- C12N15/90—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
-
- 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
- C12N5/10—Cells modified by introduction of foreign genetic material
-
- 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
- A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
-
- 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
- A01K2227/101—Bovine
-
- 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
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Environmental Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Animal Behavior & Ethology (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Biodiversity & Conservation Biology (AREA)
- Animal Husbandry (AREA)
- Cell Biology (AREA)
- Transplantation (AREA)
- Reproductive Health (AREA)
- Public Health (AREA)
- Mycology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU2017202379A AU2017202379B2 (en) | 2011-02-25 | 2017-04-11 | Gene edited livestock animals and methods of making the same |
| AU2019264610A AU2019264610A1 (en) | 2011-02-25 | 2019-11-14 | Genetically modified animals and methods for making the same |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161446651P | 2011-02-25 | 2011-02-25 | |
| US61/446,651 | 2011-02-25 | ||
| PCT/US2012/026500 WO2012116274A2 (en) | 2011-02-25 | 2012-02-24 | Genetically modified animals and methods for making the same |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2017202379A Division AU2017202379B2 (en) | 2011-02-25 | 2017-04-11 | Gene edited livestock animals and methods of making the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2012222144A1 AU2012222144A1 (en) | 2013-10-10 |
| AU2012222144B2 true AU2012222144B2 (en) | 2017-04-27 |
Family
ID=46719944
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2012222144A Active AU2012222144B2 (en) | 2011-02-25 | 2012-02-24 | Genetically modified animals and methods for making the same |
| AU2017202379A Active AU2017202379B2 (en) | 2011-02-25 | 2017-04-11 | Gene edited livestock animals and methods of making the same |
| AU2019264610A Abandoned AU2019264610A1 (en) | 2011-02-25 | 2019-11-14 | Genetically modified animals and methods for making the same |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2017202379A Active AU2017202379B2 (en) | 2011-02-25 | 2017-04-11 | Gene edited livestock animals and methods of making the same |
| AU2019264610A Abandoned AU2019264610A1 (en) | 2011-02-25 | 2019-11-14 | Genetically modified animals and methods for making the same |
Country Status (13)
| Country | Link |
|---|---|
| US (3) | US20120222143A1 (enExample) |
| EP (3) | EP3450563A1 (enExample) |
| JP (4) | JP2014509195A (enExample) |
| KR (1) | KR20140046408A (enExample) |
| CN (4) | CN107090470B (enExample) |
| AR (1) | AR085507A1 (enExample) |
| AU (3) | AU2012222144B2 (enExample) |
| BR (1) | BR112013021785A8 (enExample) |
| CA (1) | CA2828239C (enExample) |
| CL (1) | CL2013002438A1 (enExample) |
| EA (1) | EA201391234A1 (enExample) |
| MX (2) | MX363013B (enExample) |
| WO (1) | WO2012116274A2 (enExample) |
Families Citing this family (75)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011053982A2 (en) | 2009-11-02 | 2011-05-05 | University Of Washington | Therapeutic nuclease compositions and methods |
| BR112012020257A8 (pt) * | 2010-02-11 | 2018-02-14 | Recombinetics Inc | métodos e aparelhos para produzir artiodátilos transgênicos |
| US10920242B2 (en) | 2011-02-25 | 2021-02-16 | Recombinetics, Inc. | Non-meiotic allele introgression |
| US9528124B2 (en) * | 2013-08-27 | 2016-12-27 | Recombinetics, Inc. | Efficient non-meiotic allele introgression |
| JP6063450B2 (ja) | 2011-04-29 | 2017-01-18 | ユニヴァーシティ オブ ワシントン | 治療用ヌクレアーゼ組成物および方法 |
| US8497124B2 (en) * | 2011-12-05 | 2013-07-30 | Factor Bioscience Inc. | Methods and products for reprogramming cells to a less differentiated state |
| US9179935B2 (en) * | 2012-01-13 | 2015-11-10 | The Board Of Trustees Of The Leland Stanford Junior University | Mechanical biomarkers for oocyte and embryo viability |
| AU2013204327B2 (en) * | 2012-04-20 | 2016-09-01 | Aviagen | Cell transfection method |
| CA3133545C (en) * | 2012-05-25 | 2023-08-08 | Cellectis | Use of pre t alpha or functional variant thereof for expanding tcr alpha deficient t cells |
| AR091482A1 (es) * | 2012-06-21 | 2015-02-04 | Recombinetics Inc | Celulas modificadas geneticamente y metodos par su obtencion |
| WO2013191769A1 (en) * | 2012-06-22 | 2013-12-27 | Mayo Foundation For Medical Education And Research | Genome editing |
| US10058078B2 (en) | 2012-07-31 | 2018-08-28 | Recombinetics, Inc. | Production of FMDV-resistant livestock by allele substitution |
| GB201216564D0 (en) * | 2012-09-17 | 2012-10-31 | Univ Edinburgh | Genetically edited animal |
| CA2889502A1 (en) * | 2012-10-30 | 2014-05-08 | Recombinetics, Inc. | Control of sexual maturation in animals |
| BR122019025681B1 (pt) * | 2012-11-01 | 2023-04-18 | Factor Bioscience Inc | Método para inserir uma sequência de ácido nucleico em uma localização segura de um genoma de uma célula |
| CN102964431B (zh) * | 2012-12-03 | 2014-05-07 | 中国农业科学院北京畜牧兽医研究所 | 一对特异识别肌肉生长抑制素基因的多肽及其编码基因和应用 |
| US9708589B2 (en) | 2012-12-18 | 2017-07-18 | Monsanto Technology Llc | Compositions and methods for custom site-specific DNA recombinases |
| WO2014110552A1 (en) * | 2013-01-14 | 2014-07-17 | Recombinetics, Inc. | Hornless livestock |
| US10793867B2 (en) | 2013-03-15 | 2020-10-06 | Monsanto Technology, Llc | Methods for targeted transgene-integration using custom site-specific DNA recombinases |
| US11039586B2 (en) | 2013-03-15 | 2021-06-22 | Monsanto Technology Llc | Creation and transmission of megaloci |
| EP2994531B1 (en) * | 2013-05-10 | 2018-03-28 | Sangamo Therapeutics, Inc. | Delivery methods and compositions for nuclease-mediated genome engineering |
| US11077144B2 (en) | 2013-05-13 | 2021-08-03 | Cellectis | CD19 specific chimeric antigen receptor and uses thereof |
| US20140359795A1 (en) * | 2013-05-31 | 2014-12-04 | Recombinetics, Inc. | Genetic techniques for making animals with sortable sperm |
| US20140359796A1 (en) * | 2013-05-31 | 2014-12-04 | Recombinetics, Inc. | Genetically sterile animals |
| US9982277B2 (en) | 2013-06-11 | 2018-05-29 | The Regents Of The University Of California | Methods and compositions for target DNA modification |
| PL3033184T3 (pl) | 2013-08-16 | 2021-09-20 | Massachusetts Institute Of Technology | Selektywne dostarczanie materiału do komórek |
| WO2015035034A1 (en) * | 2013-09-04 | 2015-03-12 | Mice With Horns, Llc | Materials and methods for correcting recessive mutations in animals |
| DE102013111099B4 (de) | 2013-10-08 | 2023-11-30 | Eberhard Karls Universität Tübingen Medizinische Fakultät | Permanente Genkorrektur mittels nukleotidmodifizierter messenger RNA |
| EP3060682B1 (en) | 2013-10-25 | 2023-08-30 | Livestock Improvement Corporation Limited | Genetic markers and uses therefor |
| HRP20192080T1 (hr) | 2013-10-31 | 2020-02-07 | Resolve Therapeutics, Llc | Terapeutske fuzije nukleaza-albumine i postupci |
| KR101554166B1 (ko) | 2013-11-13 | 2015-09-22 | 건국대학교 산학협력단 | 재조합 활성 유전자 2 유전자 적중벡터, 그 벡터가 도입된 면역세포 결핍 형질전환 미니 복제돼지 생산과 그 제조방법 및 활용 |
| KR101566498B1 (ko) | 2013-11-13 | 2015-11-06 | 건국대학교 산학협력단 | 인터루킨 2 수용체 감마 유전자 적중벡터, 그 벡터가 도입된 면역세포 결핍 형질전환 미니 복제돼지 생산과 그 제조방법 및 활용 |
| DK3492593T3 (da) * | 2013-11-13 | 2021-11-08 | Childrens Medical Center | Nukleasemedieret regulering af genekspression |
| CN103952424B (zh) * | 2014-04-23 | 2017-01-11 | 尹熙俊 | 生产mstn双侧基因敲除的双肌性状体细胞克隆猪的方法 |
| MX2016014066A (es) * | 2014-04-28 | 2017-05-03 | Recombinetics Inc | Edicion de genes multiples en cerdos. |
| CN103952405B (zh) * | 2014-05-13 | 2016-02-10 | 扬州大学 | 一种山羊mstn基因定点修饰系统及其应用 |
| MX2017003770A (es) | 2014-09-23 | 2017-06-30 | Aggenetics Inc | Materiales y metodos para la produccion de animales con pelo corto. |
| JP7523203B2 (ja) | 2014-10-31 | 2024-07-26 | マサチューセッツ インスティテュート オブ テクノロジー | 生体分子の免疫細胞への送達 |
| HK1242917A1 (zh) * | 2014-11-12 | 2018-07-06 | 重组股份有限公司 | 肿瘤抑制基因的杂合修饰和1型神经纤维瘤病的猪模型 |
| CN104450673B (zh) * | 2014-11-14 | 2017-07-21 | 中国农业大学 | 一种y染色体修饰方法及其应用 |
| CN104388560B (zh) * | 2014-11-14 | 2017-04-12 | 中国农业大学 | 一种y染色体标记方法及其应用 |
| US20180105834A1 (en) * | 2014-11-27 | 2018-04-19 | Institute Of Animal Sciences, Chinese Academy Of Agrigultural Sciences | A method of site-directed insertion to h11 locus in pigs by using site-directed cutting system |
| KR101724805B1 (ko) * | 2014-12-16 | 2017-04-11 | 서울대학교산학협력단 | 유전자 적중 물질을 이용한 조류 유전자 편집방법 및 유전자 편집 조류 |
| EP3245294A4 (en) | 2015-01-12 | 2018-05-30 | Massachusetts Institute of Technology | Gene editing through microfluidic delivery |
| EP3316898A4 (en) * | 2015-06-30 | 2019-02-27 | Regents of the University of Minnesota | HUMANIZED SKELETON MUSCLE |
| JP6925984B2 (ja) | 2015-07-09 | 2021-08-25 | マサチューセッツ インスティテュート オブ テクノロジー | 無核細胞への物質の送達 |
| US11339408B2 (en) | 2015-08-20 | 2022-05-24 | Applied Stemcell, Inc. | Nuclease with enhanced efficiency of genome editing |
| WO2017041051A1 (en) | 2015-09-04 | 2017-03-09 | Sqz Biotechnologies Company | Intracellular delivery of biomolecules to cells comprising a cell wall |
| EP3673732A3 (en) | 2015-10-27 | 2020-07-29 | Recombinetics, Inc. | Engineering of humanized car t-cells and platelets by genetic complementation |
| ES3040945T3 (en) * | 2015-10-28 | 2025-11-06 | Vertex Pharma | Materials and methods for treatment of duchenne muscular dystrophy |
| CN105543257A (zh) * | 2016-01-18 | 2016-05-04 | 安徽农业大学 | 一种pAPN基因定点修饰猪 |
| KR20230110373A (ko) * | 2016-06-14 | 2023-07-21 | 리전츠 오브 더 유니버스티 오브 미네소타 | 질환을 치료하기 위한 유전적으로 변형된 세포, 조직,및 장기 |
| CA3028074A1 (en) * | 2016-06-16 | 2018-12-20 | Oslo Universitetssykehus Hf | Improved gene editing |
| DK3478830T3 (da) | 2016-07-01 | 2024-05-21 | Resolve Therapeutics Llc | Optimerede binucleasefusioner og metoder |
| US20180084767A1 (en) | 2016-09-21 | 2018-03-29 | Recombinetics, Inc. | Animal models for cardiomyopathy |
| GB201617559D0 (en) | 2016-10-17 | 2016-11-30 | University Court Of The University Of Edinburgh The | Swine comprising modified cd163 and associated methods |
| WO2018144087A2 (en) * | 2016-11-03 | 2018-08-09 | Temple University-Of The Commonwealth System Of Higher Education | Dna plasmids for the fast generation of homologous recombination vectors for cell line development |
| CA3057159A1 (en) | 2017-04-12 | 2018-10-18 | Magenta Therapeutics Inc. | Aryl hydrocarbon receptor antagonists and uses thereof |
| CN108728477B (zh) * | 2017-04-24 | 2022-02-22 | 华东理工大学 | 一种高效的转座突变系统及构建方法 |
| EP3665279B1 (en) * | 2017-08-09 | 2023-07-19 | Benson Hill, Inc. | Compositions and methods for modifying genomes |
| US20190045761A1 (en) | 2017-08-11 | 2019-02-14 | Recombinetics, Inc. | Inducible disease models methods of making them and use in tissue complementation |
| JP7374091B2 (ja) | 2017-08-22 | 2023-11-06 | サナバイオ， エルエルシー | 可溶性インターフェロン受容体およびその使用 |
| CN111542597A (zh) | 2017-10-31 | 2020-08-14 | 美真达治疗公司 | 用于扩增造血干细胞和祖细胞的组合物和方法 |
| WO2019113375A2 (en) | 2017-12-06 | 2019-06-13 | Magenta Therapeutics, Inc. | Dosing regimens for the mobilization of hematopoietic stem and progenitor cells |
| CN108949830B (zh) * | 2018-08-03 | 2021-11-26 | 福州大学 | 一种在鱼类中实现基因组编辑、精确定点基因敲入的方法 |
| CN111793654B (zh) * | 2019-04-08 | 2022-05-24 | 中国农业大学 | 一种提高CRISPR/Cas9介导的双等位基因突变效率的方法及其应用 |
| WO2020210237A1 (en) * | 2019-04-08 | 2020-10-15 | Dna Twopointo Inc. | Transposition of nucleic acid constructs into eukaryotic genomes with a transposase from amyelois |
| WO2021087406A1 (en) | 2019-11-01 | 2021-05-06 | Magenta Therapeutics, Inc. | Dosing regimens for the mobilization of hematopoietic stem and progentor cells |
| AU2021263754A1 (en) | 2020-04-27 | 2022-12-01 | Ensoma, Inc. | Methods and compositions for transducing hematopoietic stem and progenitor cells in vivo |
| EP4308694A1 (en) | 2021-03-16 | 2024-01-24 | Magenta Therapeutics, Inc. | Dosing regimens for hematopoietic stem cell mobilization for stem cell transplants in multiple myeloma patients |
| GB202118058D0 (en) | 2021-12-14 | 2022-01-26 | Univ Warwick | Methods to increase yields in crops |
| US20250129385A1 (en) * | 2022-02-01 | 2025-04-24 | Abs Global, Inc. | Gene-editing methods for embryonic stem cells |
| GB2621813A (en) | 2022-06-30 | 2024-02-28 | Univ Newcastle | Preventing disease recurrence in Mitochondrial replacement therapy |
| WO2024036106A1 (en) * | 2022-08-08 | 2024-02-15 | The Board Of Trustees Of The Leland Stanford Junior University | Embryo microglia complementation for in vivo microglia manipulation and production of a non-human animal model for validation of gene function and therapeutic screening |
| GB202314578D0 (en) | 2023-09-22 | 2023-11-08 | Univ Manchester | Methods of producing homoplasmic modified plants or parts thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010143917A2 (en) * | 2009-06-11 | 2010-12-16 | Toolgen Incorporation | Targeted genomic rearrangements using site-specific nucleases |
| WO2011019385A1 (en) * | 2009-08-11 | 2011-02-17 | Sangamo Biosciences, Inc. | Organisms homozygous for targeted modification |
| WO2011072246A2 (en) * | 2009-12-10 | 2011-06-16 | Regents Of The University Of Minnesota | Tal effector-mediated dna modification |
Family Cites Families (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4873191A (en) | 1981-06-12 | 1989-10-10 | Ohio University | Genetic transformation of zygotes |
| US4888274A (en) | 1985-09-18 | 1989-12-19 | Yale University | RecA nucleoprotein filament and methods |
| US5731178A (en) | 1990-03-21 | 1998-03-24 | Behringwerke Aktiengesellschaft | Attachment-elements for stimulation of eukaryotic expression systems |
| US5510473A (en) | 1990-11-09 | 1996-04-23 | The United States Of American As Represented By The Secretary Of Health And Human Services | Cloning of the recA gene from thermus aquaticus YT-1 |
| US5763240A (en) | 1992-04-24 | 1998-06-09 | Sri International | In vivo homologous sequence targeting in eukaryotic cells |
| US5674992A (en) | 1992-08-28 | 1997-10-07 | Cornell Research Foundation, Inc. | CDNA encoding a recA homolog in eukaryotes |
| US5610053A (en) | 1993-04-07 | 1997-03-11 | The United States Of America As Represented By The Department Of Health And Human Services | DNA sequence which acts as a chromatin insulator element to protect expressed genes from cis-acting regulatory sequences in mammalian cells |
| US5731411A (en) | 1993-07-12 | 1998-03-24 | The United States Of America As Represented By The Department Of Health And Human Services | Promotion of homologous DNA pairing by RecA-derived peptides |
| EP0821070A1 (en) | 1996-07-22 | 1998-01-28 | Carelli, Claude Marcel Henri | Pit-1 gene polymorphism and trait selection in animals |
| US6037525A (en) | 1996-08-01 | 2000-03-14 | North Carolina State University | Method for reducing expression variability of transgenes in plant cells |
| US5948653A (en) | 1997-03-21 | 1999-09-07 | Pati; Sushma | Sequence alterations using homologous recombination |
| DE69841139D1 (de) * | 1997-07-14 | 2009-10-22 | Univ Liege | Mutationen im myostatingen steigern muskelmasse in säugetieren |
| US6541684B1 (en) | 1998-02-13 | 2003-04-01 | Trustees Of Columbia University In The City Of New York | Nucleotide sequences encoding maize RAD51 |
| US6388169B1 (en) | 1998-06-08 | 2002-05-14 | Pioneer Hi-Bred International, Inc. | Maize orthologues of bacterial RecA proteins |
| US6774213B1 (en) | 1998-07-24 | 2004-08-10 | Alberto I. Roca | Mutants of MAW motifs of RecA protein homologs, methods of making them, and their uses |
| US6632672B2 (en) | 1998-08-19 | 2003-10-14 | The Board Of Trustees Of The Leland Stanford Junior University | Methods and compositions for genomic modification |
| GB2365445A (en) | 1998-10-12 | 2002-02-20 | Geron Bio Med Ltd | Porcine occcytes with improved developmental competence |
| WO2000023606A1 (en) | 1998-10-22 | 2000-04-27 | Medical College Of Georgia Institute, Inc. | Long terminal repeat, enhancer, and insulator sequences for use in recombinant vectors |
| US6720478B1 (en) | 1999-05-05 | 2004-04-13 | Pioneer Hi-Bred International, Inc. | RAD51-like polynucleotide and uses thereof |
| IL146296A0 (en) * | 1999-05-06 | 2002-07-25 | Stem Cell Sciences Pty Ltd | Cell reprogramming |
| AU1100201A (en) | 1999-10-28 | 2001-05-08 | Board Of Trustees Of The Leland Stanford Junior University | Methods of in vivo gene transfer using a sleeping beauty transposon system |
| US6686515B1 (en) | 1999-11-23 | 2004-02-03 | Maxygen, Inc. | Homologous recombination in plants |
| ATE490338T1 (de) | 2000-02-18 | 2010-12-15 | Univ Leland Stanford Junior | Veränderte rekombinasen zur modifizierung des genoms |
| DK1311661T3 (da) | 2000-08-14 | 2012-11-26 | Us Gov Health & Human Serv | Forøget homolog rekombination medieret ved lambda-rekombinationsproteiner |
| AU2002324941A1 (en) | 2001-09-07 | 2003-03-24 | The Regents Of The University Of California | Method of generating a transgenic livestock animal |
| US20030232410A1 (en) * | 2002-03-21 | 2003-12-18 | Monika Liljedahl | Methods and compositions for using zinc finger endonucleases to enhance homologous recombination |
| US7176007B2 (en) | 2002-12-12 | 2007-02-13 | Wisconsin Alumni Research Foundation | RecA mutants |
| CA2512110A1 (en) | 2002-12-31 | 2004-07-22 | Mmi Genomics, Inc. | Compositions, methods, and systems for inferring bovine breed |
| US20040203158A1 (en) | 2003-01-15 | 2004-10-14 | Hackett Perry B. | Transposon-insulator element delivery systems |
| US7985739B2 (en) | 2003-06-04 | 2011-07-26 | The Board Of Trustees Of The Leland Stanford Junior University | Enhanced sleeping beauty transposon system and methods for using the same |
| CA2543786A1 (en) | 2003-10-24 | 2005-05-06 | Mmi Genomics, Inc. | Methods and systems for inferring traits to manage non-beef livestock |
| CA2563064A1 (en) * | 2004-04-22 | 2005-11-10 | Kirin Beer Kabushiki Kaisha | Transgenic animals and uses thereof |
| ES2679282T3 (es) * | 2004-10-22 | 2018-08-23 | Revivicor Inc. | Porcinos transgénicos que carecen de cadena ligera de inmunoglobulina endógena |
| CA2667414C (en) * | 2006-11-13 | 2015-12-29 | Sangamo Biosciences, Inc. | Methods and compositions for modification of the human glucocorticoid receptor locus |
| WO2010008562A2 (en) | 2008-07-16 | 2010-01-21 | Recombinetics | Methods and materials for producing transgenic animals |
| US20100105140A1 (en) | 2008-07-16 | 2010-04-29 | Fahrenkrug Scott C | Plaice dna transposon system |
| KR20160015400A (ko) * | 2008-08-22 | 2016-02-12 | 상가모 바이오사이언스 인코포레이티드 | 표적화된 단일가닥 분할 및 표적화된 통합을 위한 방법 및 조성물 |
| US20110023158A1 (en) * | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Bovine genome editing with zinc finger nucleases |
| US20110023140A1 (en) | 2008-12-04 | 2011-01-27 | Sigma-Aldrich Co. | Rabbit genome editing with zinc finger nucleases |
| EP2206723A1 (en) * | 2009-01-12 | 2010-07-14 | Bonas, Ulla | Modular DNA-binding domains |
| JP2013500018A (ja) * | 2009-07-24 | 2013-01-07 | 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 | ゲノム編集のための方法 |
| NZ598457A (en) | 2009-08-03 | 2014-06-27 | Recombinetics Inc | Methods and compositions for targeted gene modification |
| BR112012020257A8 (pt) | 2010-02-11 | 2018-02-14 | Recombinetics Inc | métodos e aparelhos para produzir artiodátilos transgênicos |
| CA2798988C (en) * | 2010-05-17 | 2020-03-10 | Sangamo Biosciences, Inc. | Tal-effector (tale) dna-binding polypeptides and uses thereof |
-
2012
- 2012-02-24 EP EP18199895.6A patent/EP3450563A1/en not_active Withdrawn
- 2012-02-24 EP EP12749281.7A patent/EP2678434B1/en active Active
- 2012-02-24 CN CN201611151706.3A patent/CN107090470B/zh active Active
- 2012-02-24 CN CN201280020439.XA patent/CN103930550B/zh active Active
- 2012-02-24 CA CA2828239A patent/CA2828239C/en active Active
- 2012-02-24 EP EP18204730.8A patent/EP3461898A1/en not_active Withdrawn
- 2012-02-24 CN CN201611152146.3A patent/CN107058383A/zh active Pending
- 2012-02-24 AU AU2012222144A patent/AU2012222144B2/en active Active
- 2012-02-24 BR BR112013021785A patent/BR112013021785A8/pt not_active Application Discontinuation
- 2012-02-24 EA EA201391234A patent/EA201391234A1/ru unknown
- 2012-02-24 WO PCT/US2012/026500 patent/WO2012116274A2/en not_active Ceased
- 2012-02-24 JP JP2013555596A patent/JP2014509195A/ja active Pending
- 2012-02-24 US US13/404,662 patent/US20120222143A1/en not_active Abandoned
- 2012-02-24 MX MX2013009725A patent/MX363013B/es unknown
- 2012-02-24 KR KR1020137025161A patent/KR20140046408A/ko not_active Ceased
- 2012-02-24 CN CN201610545840.5A patent/CN106417184A/zh active Pending
- 2012-02-28 AR ARP120100647A patent/AR085507A1/es not_active Application Discontinuation
- 2012-08-24 US US13/594,694 patent/US20130117870A1/en not_active Abandoned
-
2013
- 2013-08-23 CL CL2013002438A patent/CL2013002438A1/es unknown
- 2013-08-23 MX MX2019002482A patent/MX2019002482A/es unknown
-
2014
- 2014-08-15 US US14/460,841 patent/US20140351965A1/en not_active Abandoned
-
2017
- 2017-04-11 AU AU2017202379A patent/AU2017202379B2/en active Active
- 2017-05-09 JP JP2017093111A patent/JP2017184744A/ja active Pending
- 2017-05-09 JP JP2017093110A patent/JP2017184743A/ja active Pending
-
2019
- 2019-08-23 JP JP2019152894A patent/JP2020010692A/ja active Pending
- 2019-11-14 AU AU2019264610A patent/AU2019264610A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010143917A2 (en) * | 2009-06-11 | 2010-12-16 | Toolgen Incorporation | Targeted genomic rearrangements using site-specific nucleases |
| WO2011019385A1 (en) * | 2009-08-11 | 2011-02-17 | Sangamo Biosciences, Inc. | Organisms homozygous for targeted modification |
| WO2011072246A2 (en) * | 2009-12-10 | 2011-06-16 | Regents Of The University Of Minnesota | Tal effector-mediated dna modification |
Non-Patent Citations (1)
| Title |
|---|
| CHRISTIAN M et al, Genetics, 2010, 186: 757-761 * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2017202379B2 (en) | Gene edited livestock animals and methods of making the same | |
| AU2013277214B2 (en) | Genetically edited animals and methods for making the same | |
| US20190335725A1 (en) | Genetically sterile animals | |
| NZ712483B2 (en) | Genetically modified animals and methods for making the same | |
| NZ717891B2 (en) | Genetically modified animals and methods for making the same | |
| NZ615712B2 (en) | Genetically modified animals and methods for making the same | |
| HK1243127A1 (en) | Genetically modified animals and methods for making the same | |
| HK1233854A1 (en) | Genetically modified animals and methods for making the same | |
| HK1233854A (en) | Genetically modified animals and methods for making the same | |
| NZ715540B2 (en) | Genetically sterile animals |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) |