KR101904508B1 - 큰 표적화 벡터를 사용한 뉴클레아제-중재된 표적화 - Google Patents
큰 표적화 벡터를 사용한 뉴클레아제-중재된 표적화 Download PDFInfo
- Publication number
- KR101904508B1 KR101904508B1 KR1020147030262A KR20147030262A KR101904508B1 KR 101904508 B1 KR101904508 B1 KR 101904508B1 KR 1020147030262 A KR1020147030262 A KR 1020147030262A KR 20147030262 A KR20147030262 A KR 20147030262A KR 101904508 B1 KR101904508 B1 KR 101904508B1
- Authority
- KR
- South Korea
- Prior art keywords
- nucleic acid
- acid sequence
- delete delete
- sequence
- human
- 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
- 101710163270 Nuclease Proteins 0.000 title claims abstract description 109
- 230000008685 targeting Effects 0.000 title claims description 78
- 239000013598 vector Substances 0.000 title claims description 43
- 230000001404 mediated effect Effects 0.000 title description 4
- 238000000034 method Methods 0.000 claims abstract description 67
- 230000006801 homologous recombination Effects 0.000 claims abstract description 16
- 238000002744 homologous recombination Methods 0.000 claims abstract description 16
- 230000005782 double-strand break Effects 0.000 claims abstract description 15
- 230000005783 single-strand break Effects 0.000 claims abstract description 14
- 150000007523 nucleic acids Chemical class 0.000 claims description 464
- 108020004707 nucleic acids Proteins 0.000 claims description 246
- 102000039446 nucleic acids Human genes 0.000 claims description 246
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 208
- 238000011144 upstream manufacturing Methods 0.000 claims description 120
- 108700028369 Alleles Proteins 0.000 claims description 116
- 108090000623 proteins and genes Proteins 0.000 claims description 62
- 201000010099 disease Diseases 0.000 claims description 48
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 48
- 108700008625 Reporter Genes Proteins 0.000 claims description 41
- 238000012217 deletion Methods 0.000 claims description 41
- 230000037430 deletion Effects 0.000 claims description 41
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims description 36
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims description 36
- 230000001105 regulatory effect Effects 0.000 claims description 31
- 102000004169 proteins and genes Human genes 0.000 claims description 28
- 230000006798 recombination Effects 0.000 claims description 21
- 238000005215 recombination Methods 0.000 claims description 21
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 16
- 239000011701 zinc Substances 0.000 claims description 16
- 229910052725 zinc Inorganic materials 0.000 claims description 16
- 101000998953 Homo sapiens Immunoglobulin heavy variable 1-2 Proteins 0.000 claims description 14
- 102100036887 Immunoglobulin heavy variable 1-2 Human genes 0.000 claims description 14
- 230000014509 gene expression Effects 0.000 claims description 14
- 241001529936 Murinae Species 0.000 claims description 13
- 238000004458 analytical method Methods 0.000 claims description 13
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 9
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 claims description 7
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 claims description 7
- 230000035772 mutation Effects 0.000 claims description 7
- 230000010354 integration Effects 0.000 claims description 6
- 210000001161 mammalian embryo Anatomy 0.000 claims description 6
- 101001008255 Homo sapiens Immunoglobulin kappa variable 1D-8 Proteins 0.000 claims description 4
- 101001047628 Homo sapiens Immunoglobulin kappa variable 2-29 Proteins 0.000 claims description 4
- 101001008321 Homo sapiens Immunoglobulin kappa variable 2D-26 Proteins 0.000 claims description 4
- 101001047619 Homo sapiens Immunoglobulin kappa variable 3-20 Proteins 0.000 claims description 4
- 101001008263 Homo sapiens Immunoglobulin kappa variable 3D-15 Proteins 0.000 claims description 4
- 239000003623 enhancer Substances 0.000 claims description 4
- 108020004999 messenger RNA Proteins 0.000 claims description 4
- 230000001131 transforming effect Effects 0.000 claims description 4
- 102000006395 Globulins Human genes 0.000 claims description 3
- 108010044091 Globulins Proteins 0.000 claims description 3
- 241000894007 species Species 0.000 claims description 3
- 210000002459 blastocyst Anatomy 0.000 claims description 2
- 208000004860 Blast Crisis Diseases 0.000 claims 1
- 102100022949 Immunoglobulin kappa variable 2-29 Human genes 0.000 claims 1
- 238000012239 gene modification Methods 0.000 abstract description 32
- 210000001236 prokaryotic cell Anatomy 0.000 abstract description 32
- 230000005017 genetic modification Effects 0.000 abstract description 31
- 235000013617 genetically modified food Nutrition 0.000 abstract description 31
- 210000003527 eukaryotic cell Anatomy 0.000 abstract description 19
- 239000000203 mixture Substances 0.000 abstract description 15
- 230000001737 promoting effect Effects 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 120
- 241000699666 Mus <mouse, genus> Species 0.000 description 54
- 239000003795 chemical substances by application Substances 0.000 description 41
- 108010017070 Zinc Finger Nucleases Proteins 0.000 description 26
- 210000004962 mammalian cell Anatomy 0.000 description 25
- 108020004414 DNA Proteins 0.000 description 24
- 239000002773 nucleotide Substances 0.000 description 24
- 125000003729 nucleotide group Chemical group 0.000 description 24
- 102000004190 Enzymes Human genes 0.000 description 21
- 108090000790 Enzymes Proteins 0.000 description 21
- -1 guanine phospholipid Chemical class 0.000 description 21
- 230000004568 DNA-binding Effects 0.000 description 17
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 16
- 230000000692 anti-sense effect Effects 0.000 description 16
- 239000012634 fragment Substances 0.000 description 16
- 239000003550 marker Substances 0.000 description 16
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 14
- 102000004127 Cytokines Human genes 0.000 description 12
- 108090000695 Cytokines Proteins 0.000 description 12
- 102000015696 Interleukins Human genes 0.000 description 12
- 108010063738 Interleukins Proteins 0.000 description 12
- 241000283984 Rodentia Species 0.000 description 12
- 102000002467 interleukin receptors Human genes 0.000 description 12
- 108010093036 interleukin receptors Proteins 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 238000003776 cleavage reaction Methods 0.000 description 11
- 230000007017 scission Effects 0.000 description 11
- 206010028980 Neoplasm Diseases 0.000 description 10
- 230000027455 binding Effects 0.000 description 10
- 201000011510 cancer Diseases 0.000 description 10
- 108010082025 cyan fluorescent protein Proteins 0.000 description 10
- 210000002950 fibroblast Anatomy 0.000 description 10
- 108010021843 fluorescent protein 583 Proteins 0.000 description 10
- 108091000080 Phosphotransferase Proteins 0.000 description 9
- 230000001939 inductive effect Effects 0.000 description 9
- 102000020233 phosphotransferase Human genes 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 238000006467 substitution reaction Methods 0.000 description 9
- 101001091269 Escherichia coli Hygromycin-B 4-O-kinase Proteins 0.000 description 8
- UYTPUPDQBNUYGX-UHFFFAOYSA-N Guanine Natural products O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 8
- 108010025815 Kanamycin Kinase Proteins 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- 241000700584 Simplexvirus Species 0.000 description 8
- 101001091268 Streptomyces hygroscopicus Hygromycin-B 7''-O-kinase Proteins 0.000 description 8
- 238000010459 TALEN Methods 0.000 description 8
- 102000003929 Transaminases Human genes 0.000 description 8
- 108090000340 Transaminases Proteins 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 8
- 108010045647 puromycin N-acetyltransferase Proteins 0.000 description 8
- 238000013518 transcription Methods 0.000 description 8
- 230000035897 transcription Effects 0.000 description 8
- 229940075420 xanthine Drugs 0.000 description 8
- 108010073062 Transcription Activator-Like Effectors Proteins 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 238000003780 insertion Methods 0.000 description 7
- 230000037431 insertion Effects 0.000 description 7
- 108091026890 Coding region Proteins 0.000 description 6
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 6
- 108010002350 Interleukin-2 Proteins 0.000 description 6
- 102000000588 Interleukin-2 Human genes 0.000 description 6
- 102000018697 Membrane Proteins Human genes 0.000 description 6
- 108010052285 Membrane Proteins Proteins 0.000 description 6
- 102000007999 Nuclear Proteins Human genes 0.000 description 6
- 108010089610 Nuclear Proteins Proteins 0.000 description 6
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 6
- 210000001185 bone marrow Anatomy 0.000 description 6
- 102000003675 cytokine receptors Human genes 0.000 description 6
- 108010057085 cytokine receptors Proteins 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 6
- 210000005260 human cell Anatomy 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 239000000178 monomer Substances 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 210000000130 stem cell Anatomy 0.000 description 6
- 102000003390 tumor necrosis factor Human genes 0.000 description 6
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 5
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 5
- 108091005943 CyPet Proteins 0.000 description 5
- 108010042407 Endonucleases Proteins 0.000 description 5
- 102000004533 Endonucleases Human genes 0.000 description 5
- 108060001084 Luciferase Proteins 0.000 description 5
- 239000005089 Luciferase Substances 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 108010054624 red fluorescent protein Proteins 0.000 description 5
- 229910052594 sapphire Inorganic materials 0.000 description 5
- 239000010980 sapphire Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 238000013519 translation Methods 0.000 description 5
- 208000019838 Blood disease Diseases 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 4
- 108090000144 Human Proteins Proteins 0.000 description 4
- 102000003839 Human Proteins Human genes 0.000 description 4
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 4
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 4
- 208000029578 Muscle disease Diseases 0.000 description 4
- 208000021642 Muscular disease Diseases 0.000 description 4
- 108010021466 Mutant Proteins Proteins 0.000 description 4
- 102000008300 Mutant Proteins Human genes 0.000 description 4
- 208000012902 Nervous system disease Diseases 0.000 description 4
- 108700026244 Open Reading Frames Proteins 0.000 description 4
- 102000018120 Recombinases Human genes 0.000 description 4
- 108010091086 Recombinases Proteins 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 238000004520 electroporation Methods 0.000 description 4
- 108010026638 endodeoxyribonuclease FokI Proteins 0.000 description 4
- 108020001507 fusion proteins Proteins 0.000 description 4
- 102000037865 fusion proteins Human genes 0.000 description 4
- 210000002149 gonad Anatomy 0.000 description 4
- 208000014951 hematologic disease Diseases 0.000 description 4
- 208000018706 hematopoietic system disease Diseases 0.000 description 4
- 208000026278 immune system disease Diseases 0.000 description 4
- 208000017169 kidney disease Diseases 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 210000002894 multi-fate stem cell Anatomy 0.000 description 4
- YMHOBZXQZVXHBM-UHFFFAOYSA-N 2,5-dimethoxy-4-bromophenethylamine Chemical compound COC1=CC(CCN)=C(OC)C=C1Br YMHOBZXQZVXHBM-UHFFFAOYSA-N 0.000 description 3
- 101150061877 Asic1 gene Proteins 0.000 description 3
- 102000019034 Chemokines Human genes 0.000 description 3
- 108010012236 Chemokines Proteins 0.000 description 3
- 241000579895 Chlorostilbon Species 0.000 description 3
- 241000699800 Cricetinae Species 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- 108050001049 Extracellular proteins Proteins 0.000 description 3
- 101001002470 Homo sapiens Interferon lambda-1 Proteins 0.000 description 3
- 101000853002 Homo sapiens Interleukin-25 Proteins 0.000 description 3
- 101000853000 Homo sapiens Interleukin-26 Proteins 0.000 description 3
- 101000998139 Homo sapiens Interleukin-32 Proteins 0.000 description 3
- 101001043594 Homo sapiens Low-density lipoprotein receptor-related protein 5 Proteins 0.000 description 3
- 101001128431 Homo sapiens Myeloid-derived growth factor Proteins 0.000 description 3
- 101001123448 Homo sapiens Prolactin receptor Proteins 0.000 description 3
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 3
- 101000764872 Homo sapiens Transient receptor potential cation channel subfamily A member 1 Proteins 0.000 description 3
- 102100022964 Immunoglobulin kappa variable 3-20 Human genes 0.000 description 3
- 108010002352 Interleukin-1 Proteins 0.000 description 3
- 102000000589 Interleukin-1 Human genes 0.000 description 3
- 108010065805 Interleukin-12 Proteins 0.000 description 3
- 108090000176 Interleukin-13 Proteins 0.000 description 3
- 108090000172 Interleukin-15 Proteins 0.000 description 3
- 101800003050 Interleukin-16 Proteins 0.000 description 3
- 102000013691 Interleukin-17 Human genes 0.000 description 3
- 108050003558 Interleukin-17 Proteins 0.000 description 3
- 108090000171 Interleukin-18 Proteins 0.000 description 3
- 108050009288 Interleukin-19 Proteins 0.000 description 3
- 102000007351 Interleukin-2 Receptor alpha Subunit Human genes 0.000 description 3
- 108010032774 Interleukin-2 Receptor alpha Subunit Proteins 0.000 description 3
- 102000008193 Interleukin-2 Receptor beta Subunit Human genes 0.000 description 3
- 108010060632 Interleukin-2 Receptor beta Subunit Proteins 0.000 description 3
- 108010066979 Interleukin-27 Proteins 0.000 description 3
- 108010002386 Interleukin-3 Proteins 0.000 description 3
- 108090000978 Interleukin-4 Proteins 0.000 description 3
- 108010002616 Interleukin-5 Proteins 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 108010002586 Interleukin-7 Proteins 0.000 description 3
- 102100021926 Low-density lipoprotein receptor-related protein 5 Human genes 0.000 description 3
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 3
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 3
- 102100029000 Prolactin receptor Human genes 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 3
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 3
- 108010052160 Site-specific recombinase Proteins 0.000 description 3
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 3
- 102100026186 Transient receptor potential cation channel subfamily A member 1 Human genes 0.000 description 3
- 241000545067 Venus Species 0.000 description 3
- 230000003190 augmentative effect Effects 0.000 description 3
- 210000003719 b-lymphocyte Anatomy 0.000 description 3
- 210000000748 cardiovascular system Anatomy 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 210000002249 digestive system Anatomy 0.000 description 3
- 210000002257 embryonic structure Anatomy 0.000 description 3
- 229910052876 emerald Inorganic materials 0.000 description 3
- 239000010976 emerald Substances 0.000 description 3
- 210000000750 endocrine system Anatomy 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 210000003297 immature b lymphocyte Anatomy 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 108090000681 interleukin 20 Proteins 0.000 description 3
- 210000004324 lymphatic system Anatomy 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 210000003519 mature b lymphocyte Anatomy 0.000 description 3
- 230000003387 muscular Effects 0.000 description 3
- 210000000653 nervous system Anatomy 0.000 description 3
- 230000001537 neural effect Effects 0.000 description 3
- 108020004017 nuclear receptors Proteins 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 238000003753 real-time PCR Methods 0.000 description 3
- 210000004994 reproductive system Anatomy 0.000 description 3
- 210000002345 respiratory system Anatomy 0.000 description 3
- 210000001082 somatic cell Anatomy 0.000 description 3
- 210000004989 spleen cell Anatomy 0.000 description 3
- 108091005957 yellow fluorescent proteins Proteins 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 2
- 101150008942 J gene Proteins 0.000 description 2
- 101150117115 V gene Proteins 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 210000001106 artificial yeast chromosome Anatomy 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 102000023732 binding proteins Human genes 0.000 description 2
- 108091008324 binding proteins Proteins 0.000 description 2
- 230000002759 chromosomal effect Effects 0.000 description 2
- 108010050663 endodeoxyribonuclease CreI Proteins 0.000 description 2
- 238000010362 genome editing Methods 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000002229 urogenital system Anatomy 0.000 description 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000282994 Cervidae Species 0.000 description 1
- 230000004544 DNA amplification Effects 0.000 description 1
- 101100239628 Danio rerio myca gene Proteins 0.000 description 1
- 101000854886 Homo sapiens Immunoglobulin iota chain Proteins 0.000 description 1
- 101001139134 Homo sapiens Krueppel-like factor 4 Proteins 0.000 description 1
- 101000984042 Homo sapiens Protein lin-28 homolog A 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
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000009786 Immunoglobulin Constant Regions Human genes 0.000 description 1
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 102100020744 Immunoglobulin iota chain Human genes 0.000 description 1
- 102100020677 Krueppel-like factor 4 Human genes 0.000 description 1
- 101150039798 MYC gene Proteins 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000286209 Phasianidae Species 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102100025460 Protein lin-28 homolog A Human genes 0.000 description 1
- 101100247004 Rattus norvegicus Qsox1 gene Proteins 0.000 description 1
- 101150086694 SLC22A3 gene Proteins 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 101100459258 Xenopus laevis myc-a gene Proteins 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000000447 dimerizing effect Effects 0.000 description 1
- 210000001671 embryonic stem cell Anatomy 0.000 description 1
- 238000010195 expression analysis Methods 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000003205 genotyping method 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
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 241001515942 marmosets Species 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000008672 reprogramming Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000010809 targeting technique Methods 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
Images
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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
- C07K14/7155—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for interleukins [IL]
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Cell Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Toxicology (AREA)
- Mycology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Veterinary Medicine (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Enzymes And Modification Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261638267P | 2012-04-25 | 2012-04-25 | |
| US61/638,267 | 2012-04-25 | ||
| PCT/US2013/038165 WO2013163394A1 (en) | 2012-04-25 | 2013-04-25 | Nuclease-mediated targeting with large targeting vectors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20150004816A KR20150004816A (ko) | 2015-01-13 |
| KR101904508B1 true KR101904508B1 (ko) | 2018-10-04 |
Family
ID=48289700
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020147030262A Active KR101904508B1 (ko) | 2012-04-25 | 2013-04-25 | 큰 표적화 벡터를 사용한 뉴클레아제-중재된 표적화 |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US9834786B2 (enExample) |
| EP (1) | EP2847335B1 (enExample) |
| JP (1) | JP6275120B2 (enExample) |
| KR (1) | KR101904508B1 (enExample) |
| CN (2) | CN109536526B (enExample) |
| AU (1) | AU2013251558B2 (enExample) |
| BR (1) | BR112014026294B1 (enExample) |
| CA (1) | CA2869016C (enExample) |
| CY (1) | CY1120572T1 (enExample) |
| DK (1) | DK2847335T3 (enExample) |
| ES (1) | ES2683071T3 (enExample) |
| IL (1) | IL234905B (enExample) |
| IN (1) | IN2014DN09261A (enExample) |
| MX (1) | MX362523B (enExample) |
| PL (1) | PL2847335T3 (enExample) |
| PT (1) | PT2847335T (enExample) |
| RU (1) | RU2645475C2 (enExample) |
| SG (2) | SG10201702445TA (enExample) |
| WO (1) | WO2013163394A1 (enExample) |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6275120B2 (ja) | 2012-04-25 | 2018-02-07 | 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． | 大きい標的化ベクターによるヌクレアーゼ媒介標的化 |
| FI3597749T3 (fi) | 2012-05-25 | 2023-10-09 | Univ California | Menetelmiä ja koostumuksia rna-ohjattua kohde-dna-modifikaatiota varten ja rna-ohjattua transkription modulaatiota varten |
| PT3363902T (pt) | 2012-12-06 | 2019-12-19 | Sigma Aldrich Co Llc | Modificação e regulação de genoma baseadas em crispr |
| JP6475172B2 (ja) | 2013-02-20 | 2019-02-27 | 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． | ラットの遺伝子組換え |
| EP3456831B1 (en) | 2013-04-16 | 2021-07-14 | Regeneron Pharmaceuticals, Inc. | Targeted modification of rat genome |
| EP3988649B1 (en) | 2013-09-18 | 2024-11-27 | Kymab Limited | Methods, cells and organisms |
| 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 |
| US10787684B2 (en) * | 2013-11-19 | 2020-09-29 | President And Fellows Of Harvard College | Large gene excision and insertion |
| ES2975317T3 (es) | 2013-12-11 | 2024-07-04 | Regeneron Pharma | Métodos y composiciones para la modificación dirigida de un genoma |
| MX388127B (es) * | 2013-12-11 | 2025-03-19 | Regeneron Pharma | Metodos y composiciones para la modificacion dirigida de un genoma. |
| BR112016028564A2 (pt) * | 2014-06-06 | 2018-01-30 | Regeneron Pharma | método para modificar um locus-alvo em uma célula. |
| SG10201911411YA (en) * | 2014-06-26 | 2020-02-27 | Regeneron Pharma | Methods and compositions for targeted genetic modifications and methods of use |
| CA2963315A1 (en) | 2014-10-15 | 2016-04-21 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for generating or maintaining pluripotent cells |
| CA3176380A1 (en) | 2014-11-21 | 2016-05-26 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for targeted genetic modification using paired guide rnas |
| BR112017013104A2 (pt) * | 2014-12-19 | 2018-05-15 | Regeneron Pharma | métodos para modificar um locus genômico alvo em uma célula, para intensificar a recombinação homóloga em um locus genômico alvo em uma célula e para produzir uma geração f0 de um animal não humano. |
| BR112017019620A2 (pt) | 2015-03-16 | 2018-05-15 | Regeneron Pharmaceuticals, Inc. | ?roedor geneticamente modificado, célula ou tecido, métodos para produção de um roedor geneticamente modificado e de uma população de neurônios motores, métodos para seleção de um agente candidato para modular a disfunção neuronal motora e de um agente candidato para redução do estresse oxidativo em um neurônio motor, ácido nucleico, e, célula de roedor? |
| ES2784360T3 (es) | 2015-05-29 | 2020-09-24 | Regeneron Pharma | Animales no humanos que tienen una interrupción en un locus C9ORF72 |
| US10781453B2 (en) | 2016-09-30 | 2020-09-22 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a hexanucleotide repeat expansion in a C9ORF72 locus |
| KR20240135035A (ko) | 2017-06-27 | 2024-09-10 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화 asgr1 유전자좌를 포함하는 비인간 동물 |
| RU2019143568A (ru) | 2017-07-31 | 2021-09-02 | Регенерон Фармасьютикалс, Инк. | Способы и композиции для оценки crispr/cas-индуцированной рекомбинации с экзогенной донорной нуклеиновой кислотой in vivo |
| KR20200033259A (ko) | 2017-07-31 | 2020-03-27 | 리제너론 파마슈티칼스 인코포레이티드 | 생체내에서 CRISPR/Cas-매개된 파괴 또는 삭제 및 외인성 도너 핵산과의 CRISPR/Cas-유도된 재조합을 평가하기 위한 방법 및 조성물 |
| KR102780441B1 (ko) | 2017-07-31 | 2025-03-17 | 리제너론 파마슈티칼스 인코포레이티드 | Cas-형질전환 마우스 배아 줄기 세포 및 마우스 및 이것의 용도 |
| EP3585162B1 (en) | 2017-09-29 | 2023-08-30 | Regeneron Pharmaceuticals, Inc. | Rodents comprising a humanized ttr locus and methods of use |
| CN111565566B (zh) | 2017-11-10 | 2022-10-21 | 瑞泽恩制药公司 | 包含slc30a8突变的非人动物及使用方法 |
| JP7361031B2 (ja) | 2017-11-30 | 2023-10-13 | 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 | ヒト化ｔｒｋｂ遺伝子座を含む非ヒト動物 |
| CN111885915B (zh) | 2018-03-19 | 2023-04-28 | 瑞泽恩制药公司 | 使用crispr/cas系统对动物进行转录调制 |
| ES2974200T3 (es) | 2018-09-13 | 2024-06-26 | Regeneron Pharma | Rata nuligénica para el gen del factor H del complemento como modelo de glomerulopatía C3 |
| KR20210105914A (ko) | 2018-12-20 | 2021-08-27 | 리제너론 파마슈티칼스 인코포레이티드 | 뉴클레아제-매개 반복부 팽창 |
| AU2020253532B2 (en) | 2019-04-04 | 2024-06-20 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized coagulation factor 12 locus |
| 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 |
| SG11202111256XA (en) | 2019-06-07 | 2021-11-29 | Regeneron Pharma | Non-human animals comprising a humanized albumin locus |
| RU2722933C1 (ru) * | 2019-06-11 | 2020-06-05 | Автономная некоммерческая образовательная организация высшего образования Сколковский институт науки и технологий | Средство разрезания днк на основе cas9 белка из бактерии demequina sediminicola |
| WO2021108363A1 (en) | 2019-11-25 | 2021-06-03 | Regeneron Pharmaceuticals, Inc. | Crispr/cas-mediated upregulation of humanized ttr allele |
| JP2023511626A (ja) | 2020-01-28 | 2023-03-20 | 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 | ヒト化ｐｎｐｌａ３遺伝子座を含む非ヒト動物および使用方法 |
| WO2021158883A1 (en) | 2020-02-07 | 2021-08-12 | 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 |
| WO2021263146A2 (en) | 2020-06-26 | 2021-12-30 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized ace2 locus |
| GB2635892A (en) | 2021-03-05 | 2025-06-04 | Univ Leland Stanford Junior | In vivo DNA assembly and analysis |
| WO2023081847A1 (en) | 2021-11-04 | 2023-05-11 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a modified cacng1 locus |
| CA3238939A1 (en) | 2021-12-08 | 2023-06-15 | Gaurang Patel | Mutant myocilin disease model and uses thereof |
| US20250049006A1 (en) | 2021-12-20 | 2025-02-13 | C/O 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 |
| CA3242729A1 (en) | 2022-02-11 | 2023-08-17 | Regeneron Pharma | Compositions and methods for screening 4r tau targeting agents |
| KR20250048010A (ko) | 2022-07-29 | 2025-04-07 | 리제너론 파마슈티칼스 인코포레이티드 | 변형된 트랜스페린 수용체 좌위를 포함하는 비-인간 동물 |
| CA3261296A1 (en) | 2022-08-05 | 2024-02-08 | Regeneron Pharma | TDP-43 VARIANTS RESISTANT TO AGGREGATION |
| WO2024073679A1 (en) | 2022-09-29 | 2024-04-04 | Regeneron Pharmaceuticals, Inc. | Correction of hepatosteatosis in humanized liver animals through restoration of il6/il6r/gp130 signaling in human hepatocytes |
| EP4658066A1 (en) | 2023-02-01 | 2025-12-10 | Regeneron Pharmaceuticals, Inc. | Animals comprising a modified klhdc7b locus |
| WO2024189098A1 (en) | 2023-03-13 | 2024-09-19 | Iomx Therapeutics Ag | Platform technology for the identification of modulators of immune effector cell function |
| WO2025122754A1 (en) | 2023-12-07 | 2025-06-12 | Regeneron Pharmaceuticals, Inc. | Gaa knockout non-human animals |
| 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 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012012667A2 (en) | 2010-07-21 | 2012-01-26 | Sangamo Biosciences, Inc. | Methods and compositions for modification of a hla locus |
| WO2012018726A1 (en) | 2010-08-02 | 2012-02-09 | Cellectis Sa | Method for increasing double-strand break-induced gene targeting |
Family Cites Families (93)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5830729A (en) | 1996-04-18 | 1998-11-03 | Institut Pasteur | I Sce I-induced gene replacement and gene conversion in embryonic stem cells |
| US5830698A (en) * | 1997-03-14 | 1998-11-03 | Idec Pharmaceuticals Corporation | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same |
| CA2283740C (en) | 1997-03-14 | 2006-06-27 | Idec Pharmaceuticals Corporation | Method for integrating genes at specific sites in mammalian cells via homologous recombination and vectors for accomplishing the same |
| EP1141360A4 (en) | 1998-12-31 | 2002-11-06 | David Gladstone Inst | Transgenic rodents and rodent cell lines that express HIV receptors. |
| WO2000046386A2 (en) | 1999-02-03 | 2000-08-10 | The Children's Medical Center Corporation | Gene repair involving the induction of double-stranded dna cleavage at a chromosomal target site |
| AU776576B2 (en) * | 1999-12-06 | 2004-09-16 | Sangamo Biosciences, Inc. | Methods of using randomized libraries of zinc finger proteins for the identification of gene function |
| US6586251B2 (en) | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US7105348B2 (en) | 2000-10-31 | 2006-09-12 | 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 |
| WO2003087341A2 (en) | 2002-01-23 | 2003-10-23 | The University Of Utah Research Foundation | Targeted chromosomal mutagenesis using zinc finger nucleases |
| US20030232410A1 (en) | 2002-03-21 | 2003-12-18 | Monika Liljedahl | Methods and compositions for using zinc finger endonucleases to enhance homologous recombination |
| JP2006502748A (ja) | 2002-09-05 | 2006-01-26 | カリフォルニア インスティテュート オブ テクノロジー | 遺伝子ターゲッティングを誘発するキメラヌクレアーゼの使用方法 |
| US20030175968A1 (en) | 2002-10-30 | 2003-09-18 | Golic Kent G. | Gene targeting method |
| JP2006517101A (ja) * | 2003-01-13 | 2006-07-20 | エス． ラオ、マヘンドラ | 治療用産物を送達するための、増殖性の幹細胞および前駆細胞における候補分子の持続的発現 |
| US7888121B2 (en) | 2003-08-08 | 2011-02-15 | Sangamo Biosciences, Inc. | Methods and compositions for targeted cleavage and recombination |
| US8409861B2 (en) | 2003-08-08 | 2013-04-02 | Sangamo Biosciences, Inc. | Targeted deletion of cellular DNA sequences |
| EP3222715A1 (en) | 2003-08-08 | 2017-09-27 | Sangamo BioSciences, Inc. | Methods and compositions for targeted cleavage and recombination |
| AU2005287278B2 (en) | 2004-09-16 | 2011-08-04 | Sangamo Biosciences, Inc. | Compositions and methods for protein production |
| EP1802193B1 (en) | 2004-10-19 | 2014-04-30 | Regeneron Pharmaceuticals, Inc. | Method for generating a mouse homozygous for a genetic modification |
| FR2879622B1 (fr) | 2004-12-17 | 2008-02-01 | Agronomique Inst Nat Rech | Procede in vitro de production d'ovocytes ou d'oeufs presentant une modification genomique ciblee |
| US10022457B2 (en) | 2005-08-05 | 2018-07-17 | Gholam A. Peyman | Methods to regulate polarization and enhance function of cells |
| GB0615327D0 (en) | 2006-03-30 | 2006-09-13 | Univ Edinburgh | Culture medium containing kinase inhibitors and uses thereof |
| EP2505058A1 (en) | 2006-03-31 | 2012-10-03 | Medarex, Inc. | Transgenic animals expressing chimeric antibodies for use in preparing human antibodies |
| US7771967B2 (en) | 2006-12-22 | 2010-08-10 | The J. David Gladstone Institutes | Nucleic acid encoding apolipoprotein E-I3 |
| US10155038B2 (en) | 2007-02-02 | 2018-12-18 | Yale University | Cells prepared by transient transfection and methods of use thereof |
| US8110379B2 (en) | 2007-04-26 | 2012-02-07 | Sangamo Biosciences, Inc. | Targeted integration into the PPP1R12C locus |
| EP2602323B1 (en) | 2007-06-01 | 2018-02-28 | Open Monoclonal Technology, Inc. | Compositions and methods for inhibiting endogenous immunoglobin genes and producing transgenic human idiotype antibodies |
| KR20160015400A (ko) | 2008-08-22 | 2016-02-12 | 상가모 바이오사이언스 인코포레이티드 | 표적화된 단일가닥 분할 및 표적화된 통합을 위한 방법 및 조성물 |
| US20100076057A1 (en) | 2008-09-23 | 2010-03-25 | Northwestern University | TARGET DNA INTERFERENCE WITH crRNA |
| EP2180058A1 (en) | 2008-10-23 | 2010-04-28 | Cellectis | Meganuclease recombination system |
| CN102625655B (zh) | 2008-12-04 | 2016-07-06 | 桑格摩生物科学股份有限公司 | 使用锌指核酸酶在大鼠中进行基因组编辑 |
| US20110239315A1 (en) | 2009-01-12 | 2011-09-29 | Ulla Bonas | Modular dna-binding domains and methods of use |
| US8722964B2 (en) | 2009-04-23 | 2014-05-13 | Transposagen Biopharmaceuticals, Inc. | Genetically engineered or transgenic rats exhibiting a cancer phenotype due to a disruption of germline tumor suppressor genes |
| US8772008B2 (en) | 2009-05-18 | 2014-07-08 | Sangamo Biosciences, Inc. | Methods and compositions for increasing nuclease activity |
| EP2456876A2 (en) | 2009-07-24 | 2012-05-30 | Transposagen Biopharmaceuticals, Inc. | Genetically modified rat models for cytokine-cytokine signaling pathways |
| EP2493288B1 (en) * | 2009-10-28 | 2015-02-18 | Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Homologous recombination in the oocyte |
| TR201903376T4 (tr) | 2009-10-29 | 2019-04-22 | Regeneron Pharma | Çok fonksiyonlu alleller. |
| WO2011053957A2 (en) | 2009-11-02 | 2011-05-05 | Gen9, Inc. | Compositions and methods for the regulation of multiple genes of interest in a cell |
| CN102762717A (zh) | 2009-12-01 | 2012-10-31 | 日本国立癌症研究中心 | 使用大鼠胚胎干细胞构建嵌合大鼠的方法 |
| CA2783351C (en) | 2009-12-10 | 2021-09-07 | Regents Of The University Of Minnesota | Tal effector-mediated dna modification |
| EP2516652B1 (en) | 2009-12-21 | 2014-11-05 | Keygene N.V. | Improved techniques for transfecting protoplasts |
| JP2013517774A (ja) | 2010-01-22 | 2013-05-20 | ダウ アグロサイエンシィズ エルエルシー | 遺伝子改変生物における導入遺伝子の切除 |
| WO2011100058A1 (en) * | 2010-02-09 | 2011-08-18 | Sangamo Biosciences, Inc. | Targeted genomic modification with partially single-stranded donor molecules |
| CA2798988C (en) | 2010-05-17 | 2020-03-10 | Sangamo Biosciences, Inc. | Tal-effector (tale) dna-binding polypeptides and uses thereof |
| GB201009732D0 (en) * | 2010-06-10 | 2010-07-21 | Gene Bridges Gmbh | Direct cloning |
| WO2011156723A1 (en) | 2010-06-11 | 2011-12-15 | Regeneron Pharmaceuticals, Inc. | Production of fertile xy female animals from xy es cells |
| WO2012129198A1 (en) | 2011-03-23 | 2012-09-27 | Transposagen Biopharmaceuticals, Inc. | Genetically modified rat models for obesity and diabetes |
| EP2718446A2 (en) | 2011-06-07 | 2014-04-16 | Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Improved recombination efficiency by inhibition of nhej dna repair |
| CN104011071B (zh) | 2011-10-28 | 2017-11-07 | 瑞泽恩制药公司 | T细胞受体基因修饰小鼠 |
| US9637739B2 (en) | 2012-03-20 | 2017-05-02 | Vilnius University | RNA-directed DNA cleavage by the Cas9-crRNA complex |
| WO2013141680A1 (en) | 2012-03-20 | 2013-09-26 | Vilnius University | RNA-DIRECTED DNA CLEAVAGE BY THE Cas9-crRNA COMPLEX |
| JP6275120B2 (ja) | 2012-04-25 | 2018-02-07 | 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． | 大きい標的化ベクターによるヌクレアーゼ媒介標的化 |
| BR112014027813A2 (pt) | 2012-05-07 | 2017-08-08 | Dow Agrosciences Llc | métodos e composições para integração de transgenes direcionada mediada por nuclease |
| FI3597749T3 (fi) | 2012-05-25 | 2023-10-09 | Univ California | Menetelmiä ja koostumuksia rna-ohjattua kohde-dna-modifikaatiota varten ja rna-ohjattua transkription modulaatiota varten |
| CN104540382A (zh) | 2012-06-12 | 2015-04-22 | 弗·哈夫曼-拉罗切有限公司 | 用于产生条件性敲除等位基因的方法和组合物 |
| EP2877213B1 (en) | 2012-07-25 | 2020-12-02 | The Broad Institute, Inc. | Inducible dna binding proteins and genome perturbation tools and applications thereof |
| KR101656236B1 (ko) | 2012-10-23 | 2016-09-12 | 주식회사 툴젠 | 표적 DNA에 특이적인 가이드 RNA 및 Cas 단백질을 암호화하는 핵산 또는 Cas 단백질을 포함하는, 표적 DNA를 절단하기 위한 조성물 및 이의 용도 |
| PT3363902T (pt) | 2012-12-06 | 2019-12-19 | Sigma Aldrich Co Llc | Modificação e regulação de genoma baseadas em crispr |
| WO2014093479A1 (en) | 2012-12-11 | 2014-06-19 | Montana State University | Crispr (clustered regularly interspaced short palindromic repeats) rna-guided control of gene regulation |
| EP2931898B1 (en) | 2012-12-12 | 2016-03-09 | The Broad Institute, Inc. | Engineering and optimization of systems, methods and compositions for sequence manipulation with functional domains |
| ES2576126T3 (es) | 2012-12-12 | 2016-07-05 | The Broad Institute, Inc. | Modificación por tecnología genética y optimización de sistemas, métodos y composiciones enzimáticas mejorados para la manipulación de secuencias |
| PT2784162E (pt) | 2012-12-12 | 2015-08-27 | Broad Inst Inc | Engenharia de sistemas, métodos e composições guia otimizadas para a manipulação de sequências |
| EP2931899A1 (en) | 2012-12-12 | 2015-10-21 | The Broad Institute, Inc. | Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof |
| EP3434776A1 (en) | 2012-12-12 | 2019-01-30 | The Broad Institute, Inc. | Methods, models, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof |
| EP4234696A3 (en) | 2012-12-12 | 2023-09-06 | The Broad Institute Inc. | Crispr-cas component systems, methods and compositions for sequence manipulation |
| KR20150105956A (ko) | 2012-12-12 | 2015-09-18 | 더 브로드 인스티튜트, 인코퍼레이티드 | 서열 조작 및 치료적 적용을 위한 시스템, 방법 및 조성물의 전달, 유전자 조작 및 최적화 |
| US20140310830A1 (en) | 2012-12-12 | 2014-10-16 | Feng Zhang | CRISPR-Cas Nickase Systems, Methods And Compositions For Sequence Manipulation in Eukaryotes |
| EP2932421A1 (en) | 2012-12-12 | 2015-10-21 | The Broad Institute, Inc. | Methods, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof |
| US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
| EP4282970A3 (en) | 2012-12-17 | 2024-01-17 | President and Fellows of Harvard College | Rna-guided human genome engineering |
| JP6583918B2 (ja) | 2012-12-27 | 2019-10-02 | キージーン ナムローゼ フェンノートシャップ | 植物における遺伝連鎖を解消するための方法 |
| WO2014127287A1 (en) | 2013-02-14 | 2014-08-21 | Massachusetts Institute Of Technology | Method for in vivo tergated mutagenesis |
| JP6475172B2 (ja) | 2013-02-20 | 2019-02-27 | 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． | ラットの遺伝子組換え |
| CA2901676C (en) | 2013-02-25 | 2023-08-22 | Sangamo Biosciences, Inc. | Methods and compositions for enhancing nuclease-mediated gene disruption |
| JP2016507244A (ja) | 2013-02-27 | 2016-03-10 | ヘルムホルツ・ツェントルム・ミュンヒェン・ドイチェス・フォルシュンクスツェントルム・フューア・ゲズントハイト・ウント・ウムベルト（ゲーエムベーハー）Ｈｅｌｍｈｏｌｔｚ Ｚｅｎｔｒｕｍ ＭｕｅｎｃｈｅｎＤｅｕｔｓｃｈｅｓ Ｆｏｒｓｃｈｕｎｇｓｚｅｎｔｒｕｍ ｆｕｅｒ Ｇｅｓｕｎｄｈｅｉｔ ｕｎｄ Ｕｍｗｅｌｔ （ＧｍｂＨ） | Ｃａｓ９ヌクレアーゼによる卵母細胞における遺伝子編集 |
| US10612043B2 (en) | 2013-03-09 | 2020-04-07 | Agilent Technologies, Inc. | Methods of in vivo engineering of large sequences using multiple CRISPR/cas selections of recombineering events |
| AU2014235794A1 (en) | 2013-03-14 | 2015-10-22 | Caribou Biosciences, Inc. | Compositions and methods of nucleic acid-targeting nucleic acids |
| US9234213B2 (en) | 2013-03-15 | 2016-01-12 | System Biosciences, Llc | Compositions and methods directed to CRISPR/Cas genomic engineering systems |
| US20140273230A1 (en) | 2013-03-15 | 2014-09-18 | Sigma-Aldrich Co., Llc | Crispr-based genome modification and regulation |
| US20140349400A1 (en) | 2013-03-15 | 2014-11-27 | Massachusetts Institute Of Technology | Programmable Modification of DNA |
| EP2975942B1 (en) | 2013-03-21 | 2018-08-08 | Sangamo Therapeutics, Inc. | Targeted disruption of t cell receptor genes using engineered zinc finger protein nucleases |
| EP2981617B1 (en) | 2013-04-04 | 2023-07-05 | President and Fellows of Harvard College | Therapeutic uses of genome editing with crispr/cas systems |
| WO2014172458A1 (en) | 2013-04-16 | 2014-10-23 | University Of Washington Through Its Center For Commercialization | Activating an alternative pathway for homology-directed repair to stimulate targeted gene correction and genome engineering |
| EP3456831B1 (en) | 2013-04-16 | 2021-07-14 | Regeneron Pharmaceuticals, Inc. | Targeted modification of rat genome |
| WO2014172470A2 (en) | 2013-04-16 | 2014-10-23 | Whitehead Institute For Biomedical Research | Methods of mutating, modifying or modulating nucleic acid in a cell or nonhuman mammal |
| EP2796558A1 (en) | 2013-04-23 | 2014-10-29 | Rheinische Friedrich-Wilhelms-Universität Bonn | Improved gene targeting and nucleic acid carrier molecule, in particular for use in plants |
| US11306328B2 (en) | 2013-07-26 | 2022-04-19 | President And Fellows Of Harvard College | Genome engineering |
| MX388127B (es) | 2013-12-11 | 2025-03-19 | Regeneron Pharma | Metodos y composiciones para la modificacion dirigida de un genoma. |
| BR112016028564A2 (pt) | 2014-06-06 | 2018-01-30 | Regeneron Pharma | método para modificar um locus-alvo em uma célula. |
| SG10201911411YA (en) | 2014-06-26 | 2020-02-27 | Regeneron Pharma | Methods and compositions for targeted genetic modifications and methods of use |
| MX2017000646A (es) | 2014-07-15 | 2017-04-27 | Juno Therapeutics Inc | Celulas geneticamente modificadas para terapia celular adoptiva. |
| BR112017013104A2 (pt) | 2014-12-19 | 2018-05-15 | Regeneron Pharma | métodos para modificar um locus genômico alvo em uma célula, para intensificar a recombinação homóloga em um locus genômico alvo em uma célula e para produzir uma geração f0 de um animal não humano. |
-
2013
- 2013-04-25 JP JP2015509128A patent/JP6275120B2/ja active Active
- 2013-04-25 CN CN201811024942.8A patent/CN109536526B/zh active Active
- 2013-04-25 ES ES13720718.9T patent/ES2683071T3/es active Active
- 2013-04-25 US US13/870,280 patent/US9834786B2/en active Active
- 2013-04-25 CA CA2869016A patent/CA2869016C/en active Active
- 2013-04-25 EP EP13720718.9A patent/EP2847335B1/en active Active
- 2013-04-25 IN IN9261DEN2014 patent/IN2014DN09261A/en unknown
- 2013-04-25 AU AU2013251558A patent/AU2013251558B2/en active Active
- 2013-04-25 DK DK13720718.9T patent/DK2847335T3/en active
- 2013-04-25 KR KR1020147030262A patent/KR101904508B1/ko active Active
- 2013-04-25 CN CN201380030738.6A patent/CN104364380B/zh active Active
- 2013-04-25 SG SG10201702445TA patent/SG10201702445TA/en unknown
- 2013-04-25 PT PT137207189T patent/PT2847335T/pt unknown
- 2013-04-25 MX MX2014012994A patent/MX362523B/es active IP Right Grant
- 2013-04-25 PL PL13720718T patent/PL2847335T3/pl unknown
- 2013-04-25 WO PCT/US2013/038165 patent/WO2013163394A1/en not_active Ceased
- 2013-04-25 RU RU2014145942A patent/RU2645475C2/ru active
- 2013-04-25 SG SG11201406547YA patent/SG11201406547YA/en unknown
- 2013-04-25 BR BR112014026294-2A patent/BR112014026294B1/pt active IP Right Grant
-
2014
- 2014-09-30 IL IL234905A patent/IL234905B/en active IP Right Grant
-
2017
- 2017-10-24 US US15/792,112 patent/US10301646B2/en active Active
-
2018
- 2018-08-06 CY CY20181100810T patent/CY1120572T1/el unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012012667A2 (en) | 2010-07-21 | 2012-01-26 | Sangamo Biosciences, Inc. | Methods and compositions for modification of a hla locus |
| WO2012018726A1 (en) | 2010-08-02 | 2012-02-09 | Cellectis Sa | Method for increasing double-strand break-induced gene targeting |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101904508B1 (ko) | 큰 표적화 벡터를 사용한 뉴클레아제-중재된 표적화 | |
| JP7154248B2 (ja) | 標的遺伝子座を修飾するための方法及び組成物 | |
| HK1207396B (en) | Nuclease-mediated targeting with large targeting vectors | |
| HK40035693A (en) | Methods and compositions for modifying a targeted locus | |
| HK1235817A1 (en) | Methods and compositions for modifying a targeted locus | |
| HK1235817B (en) | Methods and compositions for modifying a targeted locus |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20141028 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| A201 | Request for examination | ||
| A302 | Request for accelerated examination | ||
| PA0201 | Request for examination |
Patent event code: PA02012R01D Patent event date: 20180411 Comment text: Request for Examination of Application |
|
| PA0302 | Request for accelerated examination |
Patent event date: 20180411 Patent event code: PA03022R01D Comment text: Request for Accelerated Examination |
|
| E902 | Notification of reason for refusal | ||
| PE0902 | Notice of grounds for rejection |
Comment text: Notification of reason for refusal Patent event date: 20180418 Patent event code: PE09021S01D |
|
| E701 | Decision to grant or registration of patent right | ||
| PE0701 | Decision of registration |
Patent event code: PE07011S01D Comment text: Decision to Grant Registration Patent event date: 20180810 |
|
| GRNT | Written decision to grant | ||
| PR0701 | Registration of establishment |
Comment text: Registration of Establishment Patent event date: 20180927 Patent event code: PR07011E01D |
|
| PR1002 | Payment of registration fee |
Payment date: 20180928 End annual number: 3 Start annual number: 1 |
|
| PG1601 | Publication of registration | ||
| PR1001 | Payment of annual fee |
Payment date: 20210820 Start annual number: 4 End annual number: 4 |
|
| PR1001 | Payment of annual fee |
Payment date: 20220822 Start annual number: 5 End annual number: 5 |
|
| PR1001 | Payment of annual fee |
Payment date: 20230828 Start annual number: 6 End annual number: 6 |
|
| PR1001 | Payment of annual fee |
Payment date: 20240826 Start annual number: 7 End annual number: 7 |