CA2426398C - Methods of modifying eukaryotic cells - Google Patents
Methods of modifying eukaryotic cells Download PDFInfo
- Publication number
- CA2426398C CA2426398C CA2426398A CA2426398A CA2426398C CA 2426398 C CA2426398 C CA 2426398C CA 2426398 A CA2426398 A CA 2426398A CA 2426398 A CA2426398 A CA 2426398A CA 2426398 C CA2426398 C CA 2426398C
- Authority
- CA
- Canada
- Prior art keywords
- gene
- cells
- chromosomal locus
- ltvec
- dna
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims abstract description 107
- 210000003527 eukaryotic cell Anatomy 0.000 title claims abstract description 91
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 169
- 210000004027 cell Anatomy 0.000 claims abstract description 100
- 230000008685 targeting Effects 0.000 claims abstract description 88
- 230000002759 chromosomal effect Effects 0.000 claims abstract description 80
- 239000013598 vector Substances 0.000 claims abstract description 65
- 239000012634 fragment Substances 0.000 claims abstract description 54
- 230000006801 homologous recombination Effects 0.000 claims abstract description 53
- 238000002744 homologous recombination Methods 0.000 claims abstract description 53
- 238000012239 gene modification Methods 0.000 claims abstract description 19
- 230000005017 genetic modification Effects 0.000 claims abstract description 18
- 235000013617 genetically modified food Nutrition 0.000 claims abstract description 18
- 108020004414 DNA Proteins 0.000 claims description 79
- 230000004048 modification Effects 0.000 claims description 60
- 238000012986 modification Methods 0.000 claims description 60
- 108700028369 Alleles Proteins 0.000 claims description 51
- 239000000523 sample Substances 0.000 claims description 41
- 210000001671 embryonic stem cell Anatomy 0.000 claims description 36
- 238000005516 engineering process Methods 0.000 claims description 27
- 108091026890 Coding region Proteins 0.000 claims description 25
- 230000001580 bacterial effect Effects 0.000 claims description 25
- 238000012217 deletion Methods 0.000 claims description 21
- 230000037430 deletion Effects 0.000 claims description 21
- 238000003556 assay Methods 0.000 claims description 19
- 238000012207 quantitative assay Methods 0.000 claims description 18
- 238000003753 real-time PCR Methods 0.000 claims description 16
- 238000003780 insertion Methods 0.000 claims description 15
- 230000037431 insertion Effects 0.000 claims description 15
- 230000001105 regulatory effect Effects 0.000 claims description 15
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 14
- 102000004169 proteins and genes Human genes 0.000 claims description 12
- 241000283984 Rodentia Species 0.000 claims description 10
- 238000009396 hybridization Methods 0.000 claims description 10
- 241000894007 species Species 0.000 claims description 9
- 230000004075 alteration Effects 0.000 claims description 5
- 230000004927 fusion Effects 0.000 claims description 5
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 230000004544 DNA amplification Effects 0.000 claims description 3
- 230000001588 bifunctional effect Effects 0.000 claims description 3
- 230000000052 comparative effect Effects 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims 2
- 238000013459 approach Methods 0.000 abstract description 25
- 241000699666 Mus <mouse, genus> Species 0.000 description 47
- 238000003752 polymerase chain reaction Methods 0.000 description 20
- 210000004436 artificial bacterial chromosome Anatomy 0.000 description 17
- 241000699670 Mus sp. Species 0.000 description 14
- 238000012216 screening Methods 0.000 description 14
- 230000008901 benefit Effects 0.000 description 13
- 239000003550 marker Substances 0.000 description 13
- 150000007523 nucleic acids Chemical class 0.000 description 13
- 108020004707 nucleic acids Proteins 0.000 description 11
- 102000039446 nucleic acids Human genes 0.000 description 11
- 239000002773 nucleotide Substances 0.000 description 11
- 125000003729 nucleotide group Chemical group 0.000 description 11
- 238000011144 upstream manufacturing Methods 0.000 description 11
- 241000700159 Rattus Species 0.000 description 10
- 238000010369 molecular cloning Methods 0.000 description 10
- 210000002459 blastocyst Anatomy 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 108091008146 restriction endonucleases Proteins 0.000 description 8
- 206010003694 Atrophy Diseases 0.000 description 7
- 241000588724 Escherichia coli Species 0.000 description 7
- 102000011755 Phosphoglycerate Kinase Human genes 0.000 description 7
- 101001099217 Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8) Triosephosphate isomerase Proteins 0.000 description 7
- 230000037444 atrophy Effects 0.000 description 7
- 238000004520 electroporation Methods 0.000 description 7
- 210000003205 muscle Anatomy 0.000 description 7
- 239000013612 plasmid Substances 0.000 description 7
- 108700008625 Reporter Genes Proteins 0.000 description 6
- 108020004705 Codon Proteins 0.000 description 5
- 108010025815 Kanamycin Kinase Proteins 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000004364 calculation method Methods 0.000 description 5
- 210000000349 chromosome Anatomy 0.000 description 5
- 238000010276 construction Methods 0.000 description 5
- 230000002068 genetic effect Effects 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 230000000977 initiatory effect Effects 0.000 description 5
- 210000000287 oocyte Anatomy 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 4
- 206010028289 Muscle atrophy Diseases 0.000 description 4
- 238000010367 cloning Methods 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000011813 knockout mouse model Methods 0.000 description 4
- 101150066555 lacZ gene Proteins 0.000 description 4
- 230000020763 muscle atrophy Effects 0.000 description 4
- 201000000585 muscular atrophy Diseases 0.000 description 4
- 230000008488 polyadenylation Effects 0.000 description 4
- 230000035935 pregnancy Effects 0.000 description 4
- 210000001938 protoplast Anatomy 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 102000053602 DNA Human genes 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 101100356230 Escherichia coli (strain K12) recT gene Proteins 0.000 description 3
- 238000002105 Southern blotting Methods 0.000 description 3
- 108091081024 Start codon Proteins 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 210000003141 lower extremity Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 210000003497 sciatic nerve Anatomy 0.000 description 3
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 3
- 238000009966 trimming Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 101100355997 Bacillus subtilis (strain 168) recA gene Proteins 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 108010051219 Cre recombinase Proteins 0.000 description 2
- 238000001712 DNA sequencing Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 101100301301 Escherichia coli (strain K12) recE gene Proteins 0.000 description 2
- 108060002716 Exonuclease Proteins 0.000 description 2
- ABPRMMYHROQBLY-NKWVEPMBSA-N Gly-Ser-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CO)NC(=O)CN)C(=O)O ABPRMMYHROQBLY-NKWVEPMBSA-N 0.000 description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241001045988 Neogene Species 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- YCCUXNNKXDGMAM-KKUMJFAQSA-N Phe-Leu-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(O)=O YCCUXNNKXDGMAM-KKUMJFAQSA-N 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 108091036066 Three prime untranslated region Proteins 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000008045 co-localization Effects 0.000 description 2
- 230000002638 denervation Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 102000013165 exonuclease Human genes 0.000 description 2
- 210000003414 extremity Anatomy 0.000 description 2
- 238000003209 gene knockout Methods 0.000 description 2
- 238000010363 gene targeting Methods 0.000 description 2
- VPZXBVLAVMBEQI-UHFFFAOYSA-N glycyl-DL-alpha-alanine Natural products OC(=O)C(C)NC(=O)CN VPZXBVLAVMBEQI-UHFFFAOYSA-N 0.000 description 2
- 108010025306 histidylleucine Proteins 0.000 description 2
- 238000007901 in situ hybridization Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 230000031864 metaphase Effects 0.000 description 2
- 229930182817 methionine Natural products 0.000 description 2
- 101150091879 neo gene Proteins 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 210000004940 nucleus Anatomy 0.000 description 2
- 101150047627 pgk gene Proteins 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 108010029020 prolylglycine Proteins 0.000 description 2
- 238000012163 sequencing technique Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- CXNPLSGKWMLZPZ-GIFSMMMISA-N (2r,3r,6s)-3-[[(3s)-3-amino-5-[carbamimidoyl(methyl)amino]pentanoyl]amino]-6-(4-amino-2-oxopyrimidin-1-yl)-3,6-dihydro-2h-pyran-2-carboxylic acid Chemical compound O1[C@@H](C(O)=O)[C@H](NC(=O)C[C@@H](N)CCN(C)C(N)=N)C=C[C@H]1N1C(=O)N=C(N)C=C1 CXNPLSGKWMLZPZ-GIFSMMMISA-N 0.000 description 1
- XVZCXCTYGHPNEM-IHRRRGAJSA-N (2s)-1-[(2s)-2-[[(2s)-2-amino-4-methylpentanoyl]amino]-4-methylpentanoyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(O)=O XVZCXCTYGHPNEM-IHRRRGAJSA-N 0.000 description 1
- CXRCVCURMBFFOL-FXQIFTODSA-N Ala-Ala-Pro Chemical compound C[C@H](N)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O CXRCVCURMBFFOL-FXQIFTODSA-N 0.000 description 1
- YSMPVONNIWLJML-FXQIFTODSA-N Ala-Asp-Pro Chemical compound C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N1CCC[C@H]1C(O)=O YSMPVONNIWLJML-FXQIFTODSA-N 0.000 description 1
- MVBWLRJESQOQTM-ACZMJKKPSA-N Ala-Gln-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O MVBWLRJESQOQTM-ACZMJKKPSA-N 0.000 description 1
- WMYJZJRILUVVRG-WDSKDSINSA-N Ala-Gly-Gln Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CCC(N)=O WMYJZJRILUVVRG-WDSKDSINSA-N 0.000 description 1
- NBTGEURICRTMGL-WHFBIAKZSA-N Ala-Gly-Ser Chemical compound C[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O NBTGEURICRTMGL-WHFBIAKZSA-N 0.000 description 1
- SIGTYDNEPYEXGK-ZANVPECISA-N Ala-Gly-Trp Chemical compound C1=CC=C2C(C[C@H](NC(=O)CNC(=O)[C@@H](N)C)C(O)=O)=CNC2=C1 SIGTYDNEPYEXGK-ZANVPECISA-N 0.000 description 1
- DPNZTBKGAUAZQU-DLOVCJGASA-N Ala-Leu-His Chemical compound C[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)N DPNZTBKGAUAZQU-DLOVCJGASA-N 0.000 description 1
- RAAWHFXHAACDFT-FXQIFTODSA-N Ala-Met-Asn Chemical compound CSCC[C@H](NC(=O)[C@H](C)N)C(=O)N[C@@H](CC(N)=O)C(O)=O RAAWHFXHAACDFT-FXQIFTODSA-N 0.000 description 1
- OLVCTPPSXNRGKV-GUBZILKMSA-N Ala-Pro-Pro Chemical compound C[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(O)=O)CCC1 OLVCTPPSXNRGKV-GUBZILKMSA-N 0.000 description 1
- TVUFMYKTYXTRPY-HERUPUMHSA-N Ala-Trp-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(O)=O TVUFMYKTYXTRPY-HERUPUMHSA-N 0.000 description 1
- QRIYOHQJRDHFKF-UWJYBYFXSA-N Ala-Tyr-Ser Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)C)CC1=CC=C(O)C=C1 QRIYOHQJRDHFKF-UWJYBYFXSA-N 0.000 description 1
- REWSWYIDQIELBE-FXQIFTODSA-N Ala-Val-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O REWSWYIDQIELBE-FXQIFTODSA-N 0.000 description 1
- MFAMTAVAFBPXDC-LPEHRKFASA-N Arg-Asp-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)C(=O)O MFAMTAVAFBPXDC-LPEHRKFASA-N 0.000 description 1
- QAXCZGMLVICQKS-SRVKXCTJSA-N Arg-Glu-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCN=C(N)N)N QAXCZGMLVICQKS-SRVKXCTJSA-N 0.000 description 1
- PHHRSPBBQUFULD-UWVGGRQHSA-N Arg-Gly-Lys Chemical compound C(CCN)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)N PHHRSPBBQUFULD-UWVGGRQHSA-N 0.000 description 1
- KRQSPVKUISQQFS-FJXKBIBVSA-N Arg-Gly-Thr Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCN=C(N)N KRQSPVKUISQQFS-FJXKBIBVSA-N 0.000 description 1
- YBZMTKUDWXZLIX-UWVGGRQHSA-N Arg-Leu-Gly Chemical compound [H]N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)NCC(O)=O YBZMTKUDWXZLIX-UWVGGRQHSA-N 0.000 description 1
- OGSQONVYSTZIJB-WDSOQIARSA-N Arg-Leu-Trp Chemical compound CC(C)C[C@H](NC(=O)[C@@H](N)CCCN=C(N)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(O)=O OGSQONVYSTZIJB-WDSOQIARSA-N 0.000 description 1
- VUGWHBXPMAHEGZ-SRVKXCTJSA-N Arg-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCCN=C(N)N VUGWHBXPMAHEGZ-SRVKXCTJSA-N 0.000 description 1
- ZJBUILVYSXQNSW-YTWAJWBKSA-N Arg-Thr-Pro Chemical compound C[C@H]([C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CCCN=C(N)N)N)O ZJBUILVYSXQNSW-YTWAJWBKSA-N 0.000 description 1
- AOJYORNRFWWEIV-IHRRRGAJSA-N Arg-Tyr-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CC(O)=O)C(O)=O)CC1=CC=C(O)C=C1 AOJYORNRFWWEIV-IHRRRGAJSA-N 0.000 description 1
- UXHYOWXTJLBEPG-GSSVUCPTSA-N Asn-Thr-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O UXHYOWXTJLBEPG-GSSVUCPTSA-N 0.000 description 1
- PQKSVQSMTHPRIB-ZKWXMUAHSA-N Asn-Val-Ser Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(O)=O PQKSVQSMTHPRIB-ZKWXMUAHSA-N 0.000 description 1
- XOQYDFCQPWAMSA-KKHAAJSZSA-N Asn-Val-Thr Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XOQYDFCQPWAMSA-KKHAAJSZSA-N 0.000 description 1
- XEDQMTWEYFBOIK-ACZMJKKPSA-N Asp-Ala-Glu Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(O)=O XEDQMTWEYFBOIK-ACZMJKKPSA-N 0.000 description 1
- DBWYWXNMZZYIRY-LPEHRKFASA-N Asp-Arg-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(=O)O)N)C(=O)O DBWYWXNMZZYIRY-LPEHRKFASA-N 0.000 description 1
- QQXOYLWJQUPXJU-WHFBIAKZSA-N Asp-Cys-Gly Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CS)C(=O)NCC(O)=O QQXOYLWJQUPXJU-WHFBIAKZSA-N 0.000 description 1
- DXQOQMCLWWADMU-ACZMJKKPSA-N Asp-Gln-Ser Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O DXQOQMCLWWADMU-ACZMJKKPSA-N 0.000 description 1
- YDJVIBMKAMQPPP-LAEOZQHASA-N Asp-Glu-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(O)=O YDJVIBMKAMQPPP-LAEOZQHASA-N 0.000 description 1
- RQYMKRMRZWJGHC-BQBZGAKWSA-N Asp-Gly-Met Chemical compound CSCC[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)O)N RQYMKRMRZWJGHC-BQBZGAKWSA-N 0.000 description 1
- WWOYXVBGHAHQBG-FXQIFTODSA-N Asp-Met-Asp Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(O)=O WWOYXVBGHAHQBG-FXQIFTODSA-N 0.000 description 1
- KPSHWSWFPUDEGF-FXQIFTODSA-N Asp-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC(O)=O KPSHWSWFPUDEGF-FXQIFTODSA-N 0.000 description 1
- QTIZKMMLNUMHHU-DCAQKATOSA-N Asp-Pro-His Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CC(=O)O)N)C(=O)N[C@@H](CC2=CN=CN2)C(=O)O QTIZKMMLNUMHHU-DCAQKATOSA-N 0.000 description 1
- WMLFFCRUSPNENW-ZLUOBGJFSA-N Asp-Ser-Ala Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(O)=O WMLFFCRUSPNENW-ZLUOBGJFSA-N 0.000 description 1
- ZBYLEBZCVKLPCY-FXQIFTODSA-N Asp-Ser-Arg Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ZBYLEBZCVKLPCY-FXQIFTODSA-N 0.000 description 1
- KGHLGJAXYSVNJP-WHFBIAKZSA-N Asp-Ser-Gly Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O KGHLGJAXYSVNJP-WHFBIAKZSA-N 0.000 description 1
- ITGFVUYOLWBPQW-KKHAAJSZSA-N Asp-Thr-Val Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(O)=O ITGFVUYOLWBPQW-KKHAAJSZSA-N 0.000 description 1
- LEYKQPDPZJIRTA-AQZXSJQPSA-N Asp-Trp-Thr Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H]([C@@H](C)O)C(O)=O LEYKQPDPZJIRTA-AQZXSJQPSA-N 0.000 description 1
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- URDUGPGPLNXXES-WHFBIAKZSA-N Cys-Gly-Cys Chemical compound SC[C@H](N)C(=O)NCC(=O)N[C@@H](CS)C(O)=O URDUGPGPLNXXES-WHFBIAKZSA-N 0.000 description 1
- CUXIOFHFFXNUGG-HTFCKZLJSA-N Cys-Ile-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)O)NC(=O)[C@H](CS)N CUXIOFHFFXNUGG-HTFCKZLJSA-N 0.000 description 1
- BLGNLNRBABWDST-CIUDSAMLSA-N Cys-Leu-Asp Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CS)N BLGNLNRBABWDST-CIUDSAMLSA-N 0.000 description 1
- BCWIFCLVCRAIQK-ZLUOBGJFSA-N Cys-Ser-Cys Chemical compound C([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CS)N)O BCWIFCLVCRAIQK-ZLUOBGJFSA-N 0.000 description 1
- KZZYVYWSXMFYEC-DCAQKATOSA-N Cys-Val-Leu Chemical compound [H]N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O KZZYVYWSXMFYEC-DCAQKATOSA-N 0.000 description 1
- 108020003215 DNA Probes Proteins 0.000 description 1
- 239000003298 DNA probe Substances 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 101001091269 Escherichia coli Hygromycin-B 4-O-kinase Proteins 0.000 description 1
- 241000701959 Escherichia virus Lambda Species 0.000 description 1
- 108091029865 Exogenous DNA Proteins 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 102100040669 F-box only protein 32 Human genes 0.000 description 1
- 101710191029 F-box only protein 32 Proteins 0.000 description 1
- 108010046276 FLP recombinase Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- HHWQMFIGMMOVFK-WDSKDSINSA-N Gln-Ala-Gly Chemical compound OC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O HHWQMFIGMMOVFK-WDSKDSINSA-N 0.000 description 1
- IKDOHQHEFPPGJG-FXQIFTODSA-N Gln-Asp-Glu Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O IKDOHQHEFPPGJG-FXQIFTODSA-N 0.000 description 1
- DRDSQGHKTLSNEA-GLLZPBPUSA-N Gln-Glu-Thr Chemical compound [H]N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O DRDSQGHKTLSNEA-GLLZPBPUSA-N 0.000 description 1
- FQCILXROGNOZON-YUMQZZPRSA-N Gln-Pro-Gly Chemical compound NC(=O)CC[C@H](N)C(=O)N1CCC[C@H]1C(=O)NCC(O)=O FQCILXROGNOZON-YUMQZZPRSA-N 0.000 description 1
- JPHYJQHPILOKHC-ACZMJKKPSA-N Glu-Asp-Asp Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O JPHYJQHPILOKHC-ACZMJKKPSA-N 0.000 description 1
- ZZIFPJZQHRJERU-WDSKDSINSA-N Glu-Cys-Gly Chemical compound OC(=O)CC[C@H](N)C(=O)N[C@@H](CS)C(=O)NCC(O)=O ZZIFPJZQHRJERU-WDSKDSINSA-N 0.000 description 1
- ILGFBUGLBSAQQB-GUBZILKMSA-N Glu-Glu-Arg Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O ILGFBUGLBSAQQB-GUBZILKMSA-N 0.000 description 1
- YLJHCWNDBKKOEB-IHRRRGAJSA-N Glu-Glu-Phe Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O YLJHCWNDBKKOEB-IHRRRGAJSA-N 0.000 description 1
- OPAINBJQDQTGJY-JGVFFNPUSA-N Glu-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CCC(=O)O)N)C(=O)O OPAINBJQDQTGJY-JGVFFNPUSA-N 0.000 description 1
- DNPCBMNFQVTHMA-DCAQKATOSA-N Glu-Leu-Gln Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O DNPCBMNFQVTHMA-DCAQKATOSA-N 0.000 description 1
- DXVOKNVIKORTHQ-GUBZILKMSA-N Glu-Pro-Glu Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(O)=O DXVOKNVIKORTHQ-GUBZILKMSA-N 0.000 description 1
- TWYSSILQABLLME-HJGDQZAQSA-N Glu-Thr-Arg Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O TWYSSILQABLLME-HJGDQZAQSA-N 0.000 description 1
- BDISFWMLMNBTGP-NUMRIWBASA-N Glu-Thr-Asp Chemical compound [H]N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(O)=O BDISFWMLMNBTGP-NUMRIWBASA-N 0.000 description 1
- OGCIHJPYKVSMTE-YUMQZZPRSA-N Gly-Arg-Glu Chemical compound [H]NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(O)=O OGCIHJPYKVSMTE-YUMQZZPRSA-N 0.000 description 1
- CIMULJZTTOBOPN-WHFBIAKZSA-N Gly-Asn-Asn Chemical compound NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O CIMULJZTTOBOPN-WHFBIAKZSA-N 0.000 description 1
- SIYTVHWNKGIGMD-HOTGVXAUSA-N Gly-His-Trp Chemical compound C1=CC=C2C(=C1)C(=CN2)C[C@@H](C(=O)O)NC(=O)[C@H](CC3=CN=CN3)NC(=O)CN SIYTVHWNKGIGMD-HOTGVXAUSA-N 0.000 description 1
- YIFUFYZELCMPJP-YUMQZZPRSA-N Gly-Leu-Cys Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(O)=O YIFUFYZELCMPJP-YUMQZZPRSA-N 0.000 description 1
- ULZCYBYDTUMHNF-IUCAKERBSA-N Gly-Leu-Glu Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(O)=O ULZCYBYDTUMHNF-IUCAKERBSA-N 0.000 description 1
- UUYBFNKHOCJCHT-VHSXEESVSA-N Gly-Leu-Pro Chemical compound CC(C)C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)CN UUYBFNKHOCJCHT-VHSXEESVSA-N 0.000 description 1
- BMWFDYIYBAFROD-WPRPVWTQSA-N Gly-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)CN BMWFDYIYBAFROD-WPRPVWTQSA-N 0.000 description 1
- FGPLUIQCSKGLTI-WDSKDSINSA-N Gly-Ser-Glu Chemical compound NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CCC(O)=O FGPLUIQCSKGLTI-WDSKDSINSA-N 0.000 description 1
- WNGHUXFWEWTKAO-YUMQZZPRSA-N Gly-Ser-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CO)NC(=O)CN WNGHUXFWEWTKAO-YUMQZZPRSA-N 0.000 description 1
- LYZYGGWCBLBDMC-QWHCGFSZSA-N Gly-Tyr-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=C(C=C2)O)NC(=O)CN)C(=O)O LYZYGGWCBLBDMC-QWHCGFSZSA-N 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- RVKIPWVMZANZLI-UHFFFAOYSA-N H-Lys-Trp-OH Natural products C1=CC=C2C(CC(NC(=O)C(N)CCCCN)C(O)=O)=CNC2=C1 RVKIPWVMZANZLI-UHFFFAOYSA-N 0.000 description 1
- WZBLRQQCDYYRTD-SIXJUCDHSA-N His-Ile-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)NC(=O)[C@H](CC3=CN=CN3)N WZBLRQQCDYYRTD-SIXJUCDHSA-N 0.000 description 1
- QEYUCKCWTMIERU-SRVKXCTJSA-N His-Lys-Asp Chemical compound C1=C(NC=N1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)O)N QEYUCKCWTMIERU-SRVKXCTJSA-N 0.000 description 1
- MIHTTYXBXIRRGV-AVGNSLFASA-N His-Met-Arg Chemical compound CSCC[C@@H](C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)NC(=O)[C@H](CC1=CN=CN1)N MIHTTYXBXIRRGV-AVGNSLFASA-N 0.000 description 1
- 101000817629 Homo sapiens Dymeclin Proteins 0.000 description 1
- GRRNUXAQVGOGFE-UHFFFAOYSA-N Hygromycin-B Natural products OC1C(NC)CC(N)C(O)C1OC1C2OC3(C(C(O)C(O)C(C(N)CO)O3)O)OC2C(O)C(CO)O1 GRRNUXAQVGOGFE-UHFFFAOYSA-N 0.000 description 1
- JDCQDJVYUXNCGF-SPOWBLRKSA-N Ile-Ser-Trp Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)O)N JDCQDJVYUXNCGF-SPOWBLRKSA-N 0.000 description 1
- HXIDVIFHRYRXLZ-NAKRPEOUSA-N Ile-Ser-Val Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)O)N HXIDVIFHRYRXLZ-NAKRPEOUSA-N 0.000 description 1
- UYODHPPSCXBNCS-XUXIUFHCSA-N Ile-Val-Leu Chemical compound CC[C@H](C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CC(C)C UYODHPPSCXBNCS-XUXIUFHCSA-N 0.000 description 1
- SENJXOPIZNYLHU-UHFFFAOYSA-N L-leucyl-L-arginine Natural products CC(C)CC(N)C(=O)NC(C(O)=O)CCCN=C(N)N SENJXOPIZNYLHU-UHFFFAOYSA-N 0.000 description 1
- TYYLDKGBCJGJGW-UHFFFAOYSA-N L-tryptophan-L-tyrosine Natural products C=1NC2=CC=CC=C2C=1CC(N)C(=O)NC(C(O)=O)CC1=CC=C(O)C=C1 TYYLDKGBCJGJGW-UHFFFAOYSA-N 0.000 description 1
- CQQGCWPXDHTTNF-GUBZILKMSA-N Leu-Ala-Glu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@H](C(O)=O)CCC(O)=O CQQGCWPXDHTTNF-GUBZILKMSA-N 0.000 description 1
- GRZSCTXVCDUIPO-SRVKXCTJSA-N Leu-Arg-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(O)=O GRZSCTXVCDUIPO-SRVKXCTJSA-N 0.000 description 1
- QUAAUWNLWMLERT-IHRRRGAJSA-N Leu-Arg-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(C)C)C(O)=O QUAAUWNLWMLERT-IHRRRGAJSA-N 0.000 description 1
- TWQIYNGNYNJUFM-NHCYSSNCSA-N Leu-Asn-Val Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(O)=O TWQIYNGNYNJUFM-NHCYSSNCSA-N 0.000 description 1
- BPANDPNDMJHFEV-CIUDSAMLSA-N Leu-Asp-Ala Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(O)=O BPANDPNDMJHFEV-CIUDSAMLSA-N 0.000 description 1
- YKNBJXOJTURHCU-DCAQKATOSA-N Leu-Asp-Arg Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCCN=C(N)N YKNBJXOJTURHCU-DCAQKATOSA-N 0.000 description 1
- ZYLJULGXQDNXDK-GUBZILKMSA-N Leu-Gln-Asp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O ZYLJULGXQDNXDK-GUBZILKMSA-N 0.000 description 1
- AXZGZMGRBDQTEY-SRVKXCTJSA-N Leu-Gln-Met Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(O)=O AXZGZMGRBDQTEY-SRVKXCTJSA-N 0.000 description 1
- KUEVMUXNILMJTK-JYJNAYRXSA-N Leu-Gln-Tyr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 KUEVMUXNILMJTK-JYJNAYRXSA-N 0.000 description 1
- WMTOVWLLDGQGCV-GUBZILKMSA-N Leu-Glu-Cys Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CS)C(=O)O)N WMTOVWLLDGQGCV-GUBZILKMSA-N 0.000 description 1
- CFZZDVMBRYFFNU-QWRGUYRKSA-N Leu-His-Gly Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)NCC(O)=O CFZZDVMBRYFFNU-QWRGUYRKSA-N 0.000 description 1
- KVOFSTUWVSQMDK-KKUMJFAQSA-N Leu-His-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)CC1=CN=CN1 KVOFSTUWVSQMDK-KKUMJFAQSA-N 0.000 description 1
- FAELBUXXFQLUAX-AJNGGQMLSA-N Leu-Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CC(C)C FAELBUXXFQLUAX-AJNGGQMLSA-N 0.000 description 1
- XVZCXCTYGHPNEM-UHFFFAOYSA-N Leu-Leu-Pro Natural products CC(C)CC(N)C(=O)NC(CC(C)C)C(=O)N1CCCC1C(O)=O XVZCXCTYGHPNEM-UHFFFAOYSA-N 0.000 description 1
- JLYUZRKPDKHUTC-WDSOQIARSA-N Leu-Pro-Trp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O JLYUZRKPDKHUTC-WDSOQIARSA-N 0.000 description 1
- AKVBOOKXVAMKSS-GUBZILKMSA-N Leu-Ser-Gln Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(O)=O AKVBOOKXVAMKSS-GUBZILKMSA-N 0.000 description 1
- XOWMDXHFSBCAKQ-SRVKXCTJSA-N Leu-Ser-Leu Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@H](C(O)=O)CC(C)C XOWMDXHFSBCAKQ-SRVKXCTJSA-N 0.000 description 1
- LINKCQUOMUDLKN-KATARQTJSA-N Leu-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC(C)C)N)O LINKCQUOMUDLKN-KATARQTJSA-N 0.000 description 1
- RNYLNYTYMXACRI-VFAJRCTISA-N Leu-Thr-Trp Chemical compound [H]N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(O)=O RNYLNYTYMXACRI-VFAJRCTISA-N 0.000 description 1
- FDBTVENULFNTAL-XQQFMLRXSA-N Leu-Val-Pro Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)O)N FDBTVENULFNTAL-XQQFMLRXSA-N 0.000 description 1
- QESXLSQLQHHTIX-RHYQMDGZSA-N Leu-Val-Thr Chemical compound CC(C)C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(O)=O QESXLSQLQHHTIX-RHYQMDGZSA-N 0.000 description 1
- GCMWRRQAKQXDED-IUCAKERBSA-N Lys-Glu-Gly Chemical compound [NH3+]CCCC[C@H]([NH3+])C(=O)N[C@@H](CCC([O-])=O)C(=O)NCC([O-])=O GCMWRRQAKQXDED-IUCAKERBSA-N 0.000 description 1
- IMAKMJCBYCSMHM-AVGNSLFASA-N Lys-Glu-Lys Chemical compound NCCCC[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(O)=O)CCCCN IMAKMJCBYCSMHM-AVGNSLFASA-N 0.000 description 1
- YWJQHDDBFAXNIR-MXAVVETBSA-N Lys-Ile-His Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CN=CN1)C(=O)O)NC(=O)[C@H](CCCCN)N YWJQHDDBFAXNIR-MXAVVETBSA-N 0.000 description 1
- GAHJXEMYXKLZRQ-AJNGGQMLSA-N Lys-Lys-Ile Chemical compound [H]N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O GAHJXEMYXKLZRQ-AJNGGQMLSA-N 0.000 description 1
- AEIIJFBQVGYVEV-YESZJQIVSA-N Lys-Phe-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCCCN)N)C(=O)O AEIIJFBQVGYVEV-YESZJQIVSA-N 0.000 description 1
- MYAPQOBHGWJZOM-UWVGGRQHSA-N Met-Gly-Leu Chemical compound CSCC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC(C)C MYAPQOBHGWJZOM-UWVGGRQHSA-N 0.000 description 1
- SODXFJOPSCXOHE-IHRRRGAJSA-N Met-Leu-Leu Chemical compound CSCC[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O SODXFJOPSCXOHE-IHRRRGAJSA-N 0.000 description 1
- PHKBGZKVOJCIMZ-SRVKXCTJSA-N Met-Pro-Arg Chemical compound CSCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(O)=O PHKBGZKVOJCIMZ-SRVKXCTJSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- YBAFDPFAUTYYRW-UHFFFAOYSA-N N-L-alpha-glutamyl-L-leucine Natural products CC(C)CC(C(O)=O)NC(=O)C(N)CCC(O)=O YBAFDPFAUTYYRW-UHFFFAOYSA-N 0.000 description 1
- 108010079364 N-glycylalanine Proteins 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- WFDAEEUZPZSMOG-SRVKXCTJSA-N Phe-Cys-Ser Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(O)=O WFDAEEUZPZSMOG-SRVKXCTJSA-N 0.000 description 1
- NKLDZIPTGKBDBB-HTUGSXCWSA-N Phe-Gln-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC1=CC=CC=C1)N)O NKLDZIPTGKBDBB-HTUGSXCWSA-N 0.000 description 1
- RORUIHAWOLADSH-HJWJTTGWSA-N Phe-Ile-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](N)CC1=CC=CC=C1 RORUIHAWOLADSH-HJWJTTGWSA-N 0.000 description 1
- PEFJUUYFEGBXFA-BZSNNMDCSA-N Phe-Lys-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=CC=C1 PEFJUUYFEGBXFA-BZSNNMDCSA-N 0.000 description 1
- ROOQMPCUFLDOSB-FHWLQOOXSA-N Phe-Phe-Gln Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCC(N)=O)C(O)=O)C1=CC=CC=C1 ROOQMPCUFLDOSB-FHWLQOOXSA-N 0.000 description 1
- BPCLGWHVPVTTFM-QWRGUYRKSA-N Phe-Ser-Gly Chemical compound [H]N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)NCC(O)=O BPCLGWHVPVTTFM-QWRGUYRKSA-N 0.000 description 1
- CYQQWUPHIZVCNY-GUBZILKMSA-N Pro-Arg-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O CYQQWUPHIZVCNY-GUBZILKMSA-N 0.000 description 1
- LXVLKXPFIDDHJG-CIUDSAMLSA-N Pro-Glu-Ser Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(O)=O LXVLKXPFIDDHJG-CIUDSAMLSA-N 0.000 description 1
- HAAQQNHQZBOWFO-LURJTMIESA-N Pro-Gly-Gly Chemical compound OC(=O)CNC(=O)CNC(=O)[C@@H]1CCCN1 HAAQQNHQZBOWFO-LURJTMIESA-N 0.000 description 1
- FKLSMYYLJHYPHH-UWVGGRQHSA-N Pro-Gly-Leu Chemical compound [H]N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O FKLSMYYLJHYPHH-UWVGGRQHSA-N 0.000 description 1
- FMLRRBDLBJLJIK-DCAQKATOSA-N Pro-Leu-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1 FMLRRBDLBJLJIK-DCAQKATOSA-N 0.000 description 1
- CPRLKHJUFAXVTD-ULQDDVLXSA-N Pro-Leu-Tyr Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O CPRLKHJUFAXVTD-ULQDDVLXSA-N 0.000 description 1
- KBUAPZAZPWNYSW-SRVKXCTJSA-N Pro-Pro-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1NCCC1 KBUAPZAZPWNYSW-SRVKXCTJSA-N 0.000 description 1
- OWQXAJQZLWHPBH-FXQIFTODSA-N Pro-Ser-Asn Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(O)=O OWQXAJQZLWHPBH-FXQIFTODSA-N 0.000 description 1
- ITUDDXVFGFEKPD-NAKRPEOUSA-N Pro-Ser-Ile Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O ITUDDXVFGFEKPD-NAKRPEOUSA-N 0.000 description 1
- OQSGBXGNAFQGGS-CYDGBPFRSA-N Pro-Val-Ile Chemical compound [H]N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O OQSGBXGNAFQGGS-CYDGBPFRSA-N 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- SMIDBHKWSYUBRZ-ACZMJKKPSA-N Ser-Glu-Ala Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(O)=O SMIDBHKWSYUBRZ-ACZMJKKPSA-N 0.000 description 1
- HJEBZBMOTCQYDN-ACZMJKKPSA-N Ser-Glu-Asp Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(O)=O HJEBZBMOTCQYDN-ACZMJKKPSA-N 0.000 description 1
- UFKPDBLKLOBMRH-XHNCKOQMSA-N Ser-Glu-Pro Chemical compound C1C[C@@H](N(C1)C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)N)C(=O)O UFKPDBLKLOBMRH-XHNCKOQMSA-N 0.000 description 1
- BPMRXBZYPGYPJN-WHFBIAKZSA-N Ser-Gly-Asn Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(O)=O BPMRXBZYPGYPJN-WHFBIAKZSA-N 0.000 description 1
- IXCHOHLPHNGFTJ-YUMQZZPRSA-N Ser-Gly-His Chemical compound C1=C(NC=N1)C[C@@H](C(=O)O)NC(=O)CNC(=O)[C@H](CO)N IXCHOHLPHNGFTJ-YUMQZZPRSA-N 0.000 description 1
- GZFAWAQTEYDKII-YUMQZZPRSA-N Ser-Gly-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)CNC(=O)[C@@H](N)CO GZFAWAQTEYDKII-YUMQZZPRSA-N 0.000 description 1
- JFWDJFULOLKQFY-QWRGUYRKSA-N Ser-Gly-Phe Chemical compound [H]N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O JFWDJFULOLKQFY-QWRGUYRKSA-N 0.000 description 1
- KDGARKCAKHBEDB-NKWVEPMBSA-N Ser-Gly-Pro Chemical compound C1C[C@@H](N(C1)C(=O)CNC(=O)[C@H](CO)N)C(=O)O KDGARKCAKHBEDB-NKWVEPMBSA-N 0.000 description 1
- DJACUBDEDBZKLQ-KBIXCLLPSA-N Ser-Ile-Glu Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(O)=O DJACUBDEDBZKLQ-KBIXCLLPSA-N 0.000 description 1
- JIPVNVNKXJLFJF-BJDJZHNGSA-N Ser-Ile-Lys Chemical compound CC[C@H](C)[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CO)N JIPVNVNKXJLFJF-BJDJZHNGSA-N 0.000 description 1
- NQZFFLBPNDLTPO-DLOVCJGASA-N Ser-Phe-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)N NQZFFLBPNDLTPO-DLOVCJGASA-N 0.000 description 1
- QMCDMHWAKMUGJE-IHRRRGAJSA-N Ser-Phe-Val Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(O)=O QMCDMHWAKMUGJE-IHRRRGAJSA-N 0.000 description 1
- JLKWJWPDXPKKHI-FXQIFTODSA-N Ser-Pro-Asn Chemical compound C1C[C@H](N(C1)C(=O)[C@H](CO)N)C(=O)N[C@@H](CC(=O)N)C(=O)O JLKWJWPDXPKKHI-FXQIFTODSA-N 0.000 description 1
- CKDXFSPMIDSMGV-GUBZILKMSA-N Ser-Pro-Val Chemical compound [H]N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C(C)C)C(O)=O CKDXFSPMIDSMGV-GUBZILKMSA-N 0.000 description 1
- PYTKULIABVRXSC-BWBBJGPYSA-N Ser-Ser-Thr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(O)=O PYTKULIABVRXSC-BWBBJGPYSA-N 0.000 description 1
- OLKICIBQRVSQMA-SRVKXCTJSA-N Ser-Ser-Tyr Chemical compound [H]N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(O)=O OLKICIBQRVSQMA-SRVKXCTJSA-N 0.000 description 1
- 101001091268 Streptomyces hygroscopicus Hygromycin-B 7''-O-kinase Proteins 0.000 description 1
- 208000035199 Tetraploidy Diseases 0.000 description 1
- DWYAUVCQDTZIJI-VZFHVOOUSA-N Thr-Ala-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(O)=O DWYAUVCQDTZIJI-VZFHVOOUSA-N 0.000 description 1
- DJDSEDOKJTZBAR-ZDLURKLDSA-N Thr-Gly-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)NCC(=O)N[C@@H](CO)C(O)=O DJDSEDOKJTZBAR-ZDLURKLDSA-N 0.000 description 1
- GXUWHVZYDAHFSV-FLBSBUHZSA-N Thr-Ile-Thr Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(O)=O GXUWHVZYDAHFSV-FLBSBUHZSA-N 0.000 description 1
- SPVHQURZJCUDQC-VOAKCMCISA-N Thr-Lys-Leu Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O SPVHQURZJCUDQC-VOAKCMCISA-N 0.000 description 1
- WYLAVUAWOUVUCA-XVSYOHENSA-N Thr-Phe-Asp Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(O)=O)C(O)=O WYLAVUAWOUVUCA-XVSYOHENSA-N 0.000 description 1
- OLFOOYQTTQSSRK-UNQGMJICSA-N Thr-Pro-Phe Chemical compound C[C@@H](O)[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 OLFOOYQTTQSSRK-UNQGMJICSA-N 0.000 description 1
- WKGAAMOJPMBBMC-IXOXFDKPSA-N Thr-Ser-Phe Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(O)=O WKGAAMOJPMBBMC-IXOXFDKPSA-N 0.000 description 1
- ZMYCLHFLHRVOEA-HEIBUPTGSA-N Thr-Thr-Ser Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(O)=O ZMYCLHFLHRVOEA-HEIBUPTGSA-N 0.000 description 1
- ZOCJFNXUVSGBQI-HSHDSVGOSA-N Thr-Trp-Arg Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@@H](CCCN=C(N)N)C(=O)O)N)O ZOCJFNXUVSGBQI-HSHDSVGOSA-N 0.000 description 1
- OGOYMQWIWHGTGH-KZVJFYERSA-N Thr-Val-Ala Chemical compound C[C@@H](O)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(O)=O OGOYMQWIWHGTGH-KZVJFYERSA-N 0.000 description 1
- AKHDFZHUPGVFEJ-YEPSODPASA-N Thr-Val-Gly Chemical compound [H]N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O AKHDFZHUPGVFEJ-YEPSODPASA-N 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- VZBWRZGNEPBRDE-HZUKXOBISA-N Trp-Ala-Pro Chemical compound C[C@@H](C(=O)N1CCC[C@@H]1C(=O)O)NC(=O)[C@H](CC2=CNC3=CC=CC=C32)N VZBWRZGNEPBRDE-HZUKXOBISA-N 0.000 description 1
- RNDWCRUOGGQDKN-UBHSHLNASA-N Trp-Ser-Asp Chemical compound [H]N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(O)=O RNDWCRUOGGQDKN-UBHSHLNASA-N 0.000 description 1
- UIRPULWLRODAEQ-QEJZJMRPSA-N Trp-Ser-Glu Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(O)=O)=CNC2=C1 UIRPULWLRODAEQ-QEJZJMRPSA-N 0.000 description 1
- XKTWZYNTLXITCY-QRTARXTBSA-N Trp-Val-Asn Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)=CNC2=C1 XKTWZYNTLXITCY-QRTARXTBSA-N 0.000 description 1
- MXKUGFHWYYKVDV-SZMVWBNQSA-N Trp-Val-Val Chemical compound CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)Cc1c[nH]c2ccccc12)C(C)C)C(O)=O MXKUGFHWYYKVDV-SZMVWBNQSA-N 0.000 description 1
- DXYWRYQRKPIGGU-BPNCWPANSA-N Tyr-Ala-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 DXYWRYQRKPIGGU-BPNCWPANSA-N 0.000 description 1
- AKFLVKKWVZMFOT-IHRRRGAJSA-N Tyr-Arg-Asn Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(O)=O AKFLVKKWVZMFOT-IHRRRGAJSA-N 0.000 description 1
- YGKVNUAKYPGORG-AVGNSLFASA-N Tyr-Asp-Glu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O YGKVNUAKYPGORG-AVGNSLFASA-N 0.000 description 1
- WVRUKYLYMFGKAN-IHRRRGAJSA-N Tyr-Glu-Glu Chemical compound OC(=O)CC[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 WVRUKYLYMFGKAN-IHRRRGAJSA-N 0.000 description 1
- KCPFDGNYAMKZQP-KBPBESRZSA-N Tyr-Gly-Leu Chemical compound [H]N[C@@H](CC1=CC=C(O)C=C1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(O)=O KCPFDGNYAMKZQP-KBPBESRZSA-N 0.000 description 1
- BJCILVZEZRDIDR-PMVMPFDFSA-N Tyr-Leu-Trp Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)C1=CC=C(O)C=C1 BJCILVZEZRDIDR-PMVMPFDFSA-N 0.000 description 1
- CDBXVDXSLPLFMD-BPNCWPANSA-N Tyr-Pro-Ala Chemical compound OC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC1=CC=C(O)C=C1 CDBXVDXSLPLFMD-BPNCWPANSA-N 0.000 description 1
- UUBKSZNKJUJQEJ-JRQIVUDYSA-N Tyr-Thr-Asp Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O UUBKSZNKJUJQEJ-JRQIVUDYSA-N 0.000 description 1
- QFHRUCJIRVILCK-YJRXYDGGSA-N Tyr-Thr-Cys Chemical compound C[C@H]([C@@H](C(=O)N[C@@H](CS)C(=O)O)NC(=O)[C@H](CC1=CC=C(C=C1)O)N)O QFHRUCJIRVILCK-YJRXYDGGSA-N 0.000 description 1
- HZWPGKAKGYJWCI-ULQDDVLXSA-N Tyr-Val-Leu Chemical compound CC(C)C[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(C)C)C(O)=O HZWPGKAKGYJWCI-ULQDDVLXSA-N 0.000 description 1
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
- CVUDMNSZAIZFAE-UHFFFAOYSA-N Val-Arg-Pro Natural products NC(N)=NCCCC(NC(=O)C(N)C(C)C)C(=O)N1CCCC1C(O)=O CVUDMNSZAIZFAE-UHFFFAOYSA-N 0.000 description 1
- DAVNYIUELQBTAP-XUXIUFHCSA-N Val-Leu-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)N DAVNYIUELQBTAP-XUXIUFHCSA-N 0.000 description 1
- MIKHIIQMRFYVOR-RCWTZXSCSA-N Val-Pro-Thr Chemical compound C[C@H]([C@@H](C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C(C)C)N)O MIKHIIQMRFYVOR-RCWTZXSCSA-N 0.000 description 1
- UGFMVXRXULGLNO-XPUUQOCRSA-N Val-Ser-Gly Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](CO)C(=O)NCC(O)=O UGFMVXRXULGLNO-XPUUQOCRSA-N 0.000 description 1
- PGQUDQYHWICSAB-NAKRPEOUSA-N Val-Ser-Ile Chemical compound CC[C@H](C)[C@@H](C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)N PGQUDQYHWICSAB-NAKRPEOUSA-N 0.000 description 1
- AYHNXCJKBLYVOA-KSZLIROESA-N Val-Trp-Pro Chemical compound CC(C)[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N3CCC[C@@H]3C(=O)O)N AYHNXCJKBLYVOA-KSZLIROESA-N 0.000 description 1
- 210000002593 Y chromosome Anatomy 0.000 description 1
- 241000209149 Zea Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 108010024078 alanyl-glycyl-serine Proteins 0.000 description 1
- 108010047495 alanylglycine Proteins 0.000 description 1
- 108010011559 alanylphenylalanine Proteins 0.000 description 1
- 108010070783 alanyltyrosine Proteins 0.000 description 1
- KOSRFJWDECSPRO-UHFFFAOYSA-N alpha-L-glutamyl-L-glutamic acid Natural products OC(=O)CCC(N)C(=O)NC(CCC(O)=O)C(O)=O KOSRFJWDECSPRO-UHFFFAOYSA-N 0.000 description 1
- 108010050025 alpha-glutamyltryptophan Proteins 0.000 description 1
- 108010043240 arginyl-leucyl-glycine Proteins 0.000 description 1
- 108010084758 arginyl-tyrosyl-aspartic acid Proteins 0.000 description 1
- 108010077245 asparaginyl-proline Proteins 0.000 description 1
- 108010093581 aspartyl-proline Proteins 0.000 description 1
- 108010038633 aspartylglutamate Proteins 0.000 description 1
- 108010047857 aspartylglycine Proteins 0.000 description 1
- 210000003578 bacterial chromosome Anatomy 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- CXNPLSGKWMLZPZ-UHFFFAOYSA-N blasticidin-S Natural products O1C(C(O)=O)C(NC(=O)CC(N)CCN(C)C(N)=N)C=CC1N1C(=O)N=C(N)C=C1 CXNPLSGKWMLZPZ-UHFFFAOYSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000007910 cell fusion Effects 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 108010069495 cysteinyltyrosine Proteins 0.000 description 1
- 230000003436 cytoskeletal effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- AFABGHUZZDYHJO-UHFFFAOYSA-N dimethyl butane Natural products CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 238000007824 enzymatic assay Methods 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000003869 genetically modified organism Nutrition 0.000 description 1
- 238000012268 genome sequencing Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 108010057083 glutamyl-aspartyl-leucine Proteins 0.000 description 1
- 108010055341 glutamyl-glutamic acid Proteins 0.000 description 1
- 108010067216 glycyl-glycyl-glycine Proteins 0.000 description 1
- XKUKSGPZAADMRA-UHFFFAOYSA-N glycyl-glycyl-glycine Natural products NCC(=O)NCC(=O)NCC(O)=O XKUKSGPZAADMRA-UHFFFAOYSA-N 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 108010092114 histidylphenylalanine Proteins 0.000 description 1
- 108010018006 histidylserine Proteins 0.000 description 1
- GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 1
- 229940097277 hygromycin b Drugs 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 108010053037 kyotorphin Proteins 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000013493 large scale plasmid preparation Methods 0.000 description 1
- 108010034529 leucyl-lysine Proteins 0.000 description 1
- 108010000761 leucylarginine Proteins 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 108010054155 lysyllysine Proteins 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000003632 microfilament Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 108091027963 non-coding RNA Proteins 0.000 description 1
- 102000042567 non-coding RNA Human genes 0.000 description 1
- 108010074082 phenylalanyl-alanyl-lysine Proteins 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 108010077112 prolyl-proline Proteins 0.000 description 1
- 108010090894 prolylleucine Proteins 0.000 description 1
- 238000003906 pulsed field gel electrophoresis Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 238000010187 selection method Methods 0.000 description 1
- 108010026333 seryl-proline Proteins 0.000 description 1
- 210000003765 sex chromosome Anatomy 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 238000010809 targeting technique Methods 0.000 description 1
- 108010040614 terminase Proteins 0.000 description 1
- 108010033670 threonyl-aspartyl-tyrosine Proteins 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 108010044292 tryptophyltyrosine Proteins 0.000 description 1
- IBIDRSSEHFLGSD-UHFFFAOYSA-N valinyl-arginine Natural products CC(C)C(N)C(=O)NC(C(O)=O)CCCN=C(N)N IBIDRSSEHFLGSD-UHFFFAOYSA-N 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
- C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
- C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Environmental Sciences (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- Mycology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Cell Biology (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24466500P | 2000-10-31 | 2000-10-31 | |
| US60/244,665 | 2000-10-31 | ||
| US09/732,234 | 2000-12-07 | ||
| US09/732,234 US6586251B2 (en) | 2000-10-31 | 2000-12-07 | Methods of modifying eukaryotic cells |
| PCT/US2001/045375 WO2002036789A2 (en) | 2000-10-31 | 2001-10-31 | Methods of modifying eukaryotic cells |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2426398A1 CA2426398A1 (en) | 2002-05-10 |
| CA2426398C true CA2426398C (en) | 2010-10-26 |
Family
ID=26936709
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2426398A Expired - Lifetime CA2426398C (en) | 2000-10-31 | 2001-10-31 | Methods of modifying eukaryotic cells |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US6586251B2 (OSRAM) |
| EP (1) | EP1399575B1 (OSRAM) |
| JP (7) | JP5339566B2 (OSRAM) |
| KR (1) | KR100833136B1 (OSRAM) |
| CN (1) | CN100497642C (OSRAM) |
| AT (1) | ATE332388T1 (OSRAM) |
| AU (2) | AU2002220048B2 (OSRAM) |
| BR (1) | BRPI0115096B1 (OSRAM) |
| CA (1) | CA2426398C (OSRAM) |
| CZ (1) | CZ304856B6 (OSRAM) |
| DE (1) | DE60121372T2 (OSRAM) |
| HU (1) | HU227639B1 (OSRAM) |
| MX (1) | MXPA03003797A (OSRAM) |
| NO (1) | NO332300B1 (OSRAM) |
| NZ (1) | NZ525511A (OSRAM) |
| PL (1) | PL204759B1 (OSRAM) |
| RU (1) | RU2290441C2 (OSRAM) |
| WO (1) | WO2002036789A2 (OSRAM) |
Families Citing this family (215)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6908744B1 (en) * | 2000-03-14 | 2005-06-21 | Regeneron Pharmaceuticals, Inc. | Methods of stimulating cartilage formation |
| AU8337701A (en) * | 2000-08-14 | 2002-02-25 | Us Health | Enhanced homologous recombination mediated by lambda recombination proteins |
| US6586251B2 (en) * | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| US20050144655A1 (en) | 2000-10-31 | 2005-06-30 | Economides Aris N. | Methods of modifying eukaryotic cells |
| GB0110029D0 (en) | 2001-04-24 | 2001-06-13 | Grosveld Frank | Transgenic animal |
| US7763466B2 (en) | 2002-05-17 | 2010-07-27 | Mount Sinai School Of Medicine Of New York University | Mesoderm and definitive endoderm cell populations |
| USRE47770E1 (en) | 2002-07-18 | 2019-12-17 | Merus N.V. | Recombinant production of mixtures of antibodies |
| PT1523496E (pt) | 2002-07-18 | 2011-09-29 | Merus B V | Produção de misturas de anticorpos de forma recombinante |
| JP2005537805A (ja) * | 2002-09-09 | 2005-12-15 | カリフォルニア インスティチュート オブ テクノロジー | ヒト化マウスを作成するための方法および組成物 |
| WO2004067725A2 (en) * | 2003-01-30 | 2004-08-12 | Regeneron Pharmaceuticals, Inc. | Methods of identifying modulators of nmur2-mediated activity |
| EP1639009B1 (en) | 2003-05-30 | 2013-02-27 | Merus B.V. | Fab library for the preparation of a mixture of antibodies |
| US20100069614A1 (en) | 2008-06-27 | 2010-03-18 | Merus B.V. | Antibody producing non-human mammals |
| EP1802193B1 (en) | 2004-10-19 | 2014-04-30 | Regeneron Pharmaceuticals, Inc. | Method for generating a mouse homozygous for a genetic modification |
| US20060117396A1 (en) * | 2004-11-30 | 2006-06-01 | Murphy Andrew J | Assay methods for identifying modulators of OPSDL3 and transgenic knockouts |
| ME00832B (me) | 2007-03-22 | 2012-03-20 | Ucb Biopharma Sprl | Vezivni proteini uključujući antitjela, derivate antitjela i fragmente antitjela, koji specifično vezuju cd154 i njihova upotreba |
| PT2336329E (pt) | 2007-06-01 | 2012-12-24 | Omt Inc | Composições e métodos para inibição de genes de imunoglobulina endógena e produção de anticorpos transgénicos humanos idiotípicos |
| CA2708776A1 (en) * | 2007-12-10 | 2009-06-18 | Aliva Biopharmaceuticals, Inc. | Methods for sequential replacement of targeted region by homologous recombination |
| EP2281050B1 (en) * | 2008-04-14 | 2014-04-02 | Sangamo BioSciences, Inc. | Linear donor constructs for targeted integration |
| US20090328240A1 (en) * | 2008-06-24 | 2009-12-31 | Sing George L | Genetically modified mice as predictors of immune response |
| DE102008002715A1 (de) * | 2008-06-27 | 2009-12-31 | Evonik Röhm Gmbh | 2-Hydroxyisobuttersäure produzierende rekombinante Zelle |
| KR102362774B1 (ko) | 2008-09-30 | 2022-02-15 | 아블렉시스, 엘엘씨 | 키메라 항체의 제조를 위한 인간 이외의 포유동물 |
| US9445581B2 (en) | 2012-03-28 | 2016-09-20 | Kymab Limited | Animal models and therapeutic molecules |
| NO2792236T3 (OSRAM) | 2009-07-08 | 2018-04-14 | ||
| ES2700852T3 (es) | 2009-10-06 | 2019-02-19 | Regeneron Pharma | Ratones modificados genéticamente e injerto |
| US20110104799A1 (en) * | 2009-10-29 | 2011-05-05 | Regeneron Pharmaceuticals, Inc. | Multifunctional Alleles |
| CN102711449B (zh) | 2009-12-10 | 2015-01-07 | 瑞泽恩制药公司 | 生产重链抗体的小鼠 |
| RS57280B1 (sr) | 2009-12-21 | 2018-08-31 | Regeneron Pharma | Humanizovani fc gamma r miševi |
| PL3095871T3 (pl) * | 2010-02-08 | 2019-10-31 | Regeneron Pharma | Mysz zawierająca wspólny łańcuch lekki |
| US20120021409A1 (en) | 2010-02-08 | 2012-01-26 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
| US9796788B2 (en) | 2010-02-08 | 2017-10-24 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
| US20130045492A1 (en) | 2010-02-08 | 2013-02-21 | Regeneron Pharmaceuticals, Inc. | Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain |
| ES2641920T3 (es) | 2010-03-31 | 2017-11-14 | Ablexis, Llc | Ingeniería genética de animales no humanos para la producción de anticuerpos quiméricos |
| WO2011159847A2 (en) | 2010-06-15 | 2011-12-22 | The Regents Of The University Of California | Receptor tyrosine kinase-like orphan receptor 1 (ror1) single chain fv antibody fragment conjugates and methods of use thereof |
| ME02902B (me) | 2010-06-22 | 2018-04-20 | Regeneron Pharma | Transgeni miševi sa modifikovanim lokusom endogenog lambda imunoglobulina |
| US10662256B2 (en) | 2010-07-26 | 2020-05-26 | Trianni, Inc. | Transgenic mammals and methods of use thereof |
| US10793829B2 (en) | 2010-07-26 | 2020-10-06 | Trianni, Inc. | Transgenic mammals and methods of use thereof |
| DK2597945T3 (da) | 2010-07-26 | 2020-09-21 | Trianni Inc | Transgene dyr og fremgangsmåder til anvendelse deraf |
| RS55495B1 (sr) | 2010-08-02 | 2017-04-28 | Regeneron Pharma | Miševi koji stvaraju vezujuće proteine koji sadrže vl domene |
| EP2638155A1 (en) | 2010-11-08 | 2013-09-18 | Kymab Limited | Cells & vertebrates for enhanced somatic hypermutation and class switch recombination |
| PT2663579T (pt) | 2011-01-14 | 2017-07-28 | Univ California | Terapêutica de anticorpos contra a proteína r0r-1 e métodos para sua utilização |
| KR102256316B1 (ko) | 2011-02-15 | 2021-05-28 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화된 ｍ－ｃｓｆ 마우스 |
| ES2946169T3 (es) | 2011-02-25 | 2023-07-13 | Regeneron Pharma | Ratones ADAM6 |
| US10920242B2 (en) | 2011-02-25 | 2021-02-16 | Recombinetics, Inc. | Non-meiotic allele introgression |
| DK2527842T3 (da) | 2011-05-12 | 2013-09-08 | Regeneron Pharma | Neuropeptidfrisætningsanalyse til natriumkanaler |
| IL273982B2 (en) * | 2011-08-05 | 2023-03-01 | Regeneron Pharma | Humanized mice possess a universal light chain |
| EP2758535B1 (en) | 2011-09-19 | 2016-11-09 | Kymab Limited | Antibodies, variable domains&chains tailored for human use |
| EP3741862A1 (en) | 2011-09-19 | 2020-11-25 | Kymab Limited | Animals, repertoires & methods for the production of human antibodies |
| EP2761008A1 (en) | 2011-09-26 | 2014-08-06 | Kymab Limited | Chimaeric surrogate light chains (slc) comprising human vpreb |
| KR20250021626A (ko) | 2011-10-17 | 2025-02-13 | 리제너론 파마슈티칼스 인코포레이티드 | 제한된 면역글로불린 중쇄 마우스 |
| US9591835B2 (en) | 2011-10-28 | 2017-03-14 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
| ES2858978T3 (es) | 2011-10-28 | 2021-09-30 | Regeneron Pharma | Ratones con receptores de linfocitos T genéticamente modificados |
| ES2741649T3 (es) | 2011-10-28 | 2020-02-11 | Regeneron Pharma | Ratones con complejo mayor de histocompatibilidad modificado genéticamente |
| CN104039133B (zh) | 2011-10-28 | 2018-05-04 | 瑞泽恩制药公司 | 表达嵌合主要组织相容性复合物(mhc)ii类分子的基因修饰小鼠 |
| US9043996B2 (en) | 2011-10-28 | 2015-06-02 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex animals |
| GB2496375A (en) | 2011-10-28 | 2013-05-15 | Kymab Ltd | A non-human assay vertebrate comprising human antibody loci and human epitope knock-in, and uses thereof |
| WO2013066735A1 (en) | 2011-10-31 | 2013-05-10 | Merck Sharp & Dohme Corp. | Nano-suspension process |
| US9253965B2 (en) | 2012-03-28 | 2016-02-09 | Kymab Limited | Animal models and therapeutic molecules |
| GB201122047D0 (en) | 2011-12-21 | 2012-02-01 | Kymab Ltd | Transgenic animals |
| BR112014015238B1 (pt) | 2011-12-20 | 2022-11-16 | Regeneron Pharmaceuticals, Inc | Método ex vivo para preparar um anticorpo que se liga a um antígeno de interesse compreendendo identificar sequências de ácido nucleico a partir de linfócitos b de camundongo geneticamente modificado pela colocação de um gene adam6 |
| HRP20192218T1 (hr) | 2012-02-01 | 2020-03-06 | Regeneron Pharmaceuticals, Inc. | Humanizirani miševi koji izražavaju teške lance koji sadrže vl domene |
| CA2865029A1 (en) | 2012-03-06 | 2013-09-12 | Regeneron Pharmaceuticals, Inc. | Common light chain mouse |
| LT2883449T (lt) | 2012-03-16 | 2018-05-10 | Regeneron Pharmaceuticals, Inc. | Histidinu modifikuoti lengvosios grandinės antikūnai ir juos gaminantys genetiškai modifikuoti graužikai |
| US20140013456A1 (en) | 2012-03-16 | 2014-01-09 | Regeneron Pharmaceuticals, Inc. | Histidine Engineered Light Chain Antibodies and Genetically Modified Non-Human Animals for Generating the Same |
| EP3539374A1 (en) | 2012-03-16 | 2019-09-18 | Regeneron Pharmaceuticals, Inc. | Non-human animals expressing ph-sensitive immunoglobulin sequences |
| CN106318951A (zh) | 2012-03-16 | 2017-01-11 | 瑞泽恩制药公司 | 生产具有ph依赖性结合特性的抗原结合蛋白的小鼠 |
| EP2831245A1 (en) | 2012-03-28 | 2015-02-04 | Kymab Limited | Transgenic non-human vertebrate for the expression of class - switched, fully human, antibodies |
| GB2502127A (en) | 2012-05-17 | 2013-11-20 | Kymab Ltd | Multivalent antibodies and in vivo methods for their production |
| US10251377B2 (en) | 2012-03-28 | 2019-04-09 | Kymab Limited | Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies |
| KR101904508B1 (ko) | 2012-04-25 | 2018-10-04 | 리제너론 파마슈티칼스 인코포레이티드 | 큰 표적화 벡터를 사용한 뉴클레아제-중재된 표적화 |
| MX364449B (es) | 2012-06-12 | 2019-04-26 | Regeneron Pharma | Animales no humanos humanizados con loci de cadena pesada de inmunoglobulina restringidos. |
| AR091482A1 (es) * | 2012-06-21 | 2015-02-04 | Recombinetics Inc | Celulas modificadas geneticamente y metodos par su obtencion |
| KR102274722B1 (ko) | 2012-08-23 | 2021-07-09 | 어젠시스 인코포레이티드 | 158p1d7 단백질에 결합하는 항체 |
| DK3489261T3 (da) | 2012-08-24 | 2020-12-14 | Univ California | Antistoffer og vacciner til anvendelse ved behandling af ror1-cancere og hæmning af metastase |
| CN108782459B (zh) | 2012-09-07 | 2021-11-05 | 再生元制药公司 | 经遗传修饰的非人动物及其使用方法 |
| UA118090C2 (uk) * | 2012-09-07 | 2018-11-26 | ДАУ АГРОСАЙЄНСІЗ ЕлЕлСі | Спосіб інтегрування послідовності нуклеїнової кислоти, що представляє інтерес, у ген fad2 у клітині сої та специфічний для локусу fad2 білок, що зв'язується, здатний індукувати спрямований розрив |
| IL299887B2 (en) | 2012-11-05 | 2024-09-01 | Regeneron Pharma | Genetically modified non-human animals and methods of use thereof |
| EP2958990B1 (en) | 2013-02-20 | 2019-10-16 | Regeneron Pharmaceuticals, Inc. | Genetic modification of rats |
| KR102714111B1 (ko) | 2013-02-20 | 2024-10-11 | 리제너론 파아마슈티컬스, 인크. | 사람화된 ｔ-세포 보조-수용체를 발현하는 마우스 |
| EP2840892B1 (en) | 2013-02-20 | 2018-04-18 | Regeneron Pharmaceuticals, Inc. | Non-human animals with modified immunoglobulin heavy chain sequences |
| US20150342163A1 (en) | 2013-02-22 | 2015-12-03 | Regeneron Pharmaceuticals, Inc. | Genetically modified major histocompatibility complex mice |
| HRP20181866T1 (hr) | 2013-02-22 | 2019-01-25 | Regeneron Pharmaceuticals, Inc. | Miševi koji izražavaju humanizirane komplekse glavne histokompatibilnosti |
| EP4249507A3 (en) | 2013-03-11 | 2023-12-27 | Regeneron Pharmaceuticals, Inc. | Transgenic mice expressing chimeric major histocompatibility complex (mhc) class ii molecules |
| JP6456351B2 (ja) | 2013-03-11 | 2019-01-23 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | キメラ主要組織適合複合体（ｍｈｃ）クラスｉ分子を発現する遺伝子導入マウス |
| EP2970437A1 (en) | 2013-03-13 | 2016-01-20 | Regeneron Pharmaceuticals, Inc. | Common light chain mouse |
| ES2942413T3 (es) | 2013-03-13 | 2023-06-01 | Regeneron Pharma | Ratones que expresan un repertorio limitado de cadenas ligeras de inmunoglobulina |
| US9788534B2 (en) | 2013-03-18 | 2017-10-17 | Kymab Limited | Animal models and therapeutic molecules |
| KR20200136508A (ko) * | 2013-04-16 | 2020-12-07 | 리제너론 파마슈티칼스 인코포레이티드 | 랫트 게놈의 표적화된 변형 |
| US9783618B2 (en) | 2013-05-01 | 2017-10-10 | Kymab Limited | Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics |
| US9783593B2 (en) | 2013-05-02 | 2017-10-10 | Kymab Limited | Antibodies, variable domains and chains tailored for human use |
| US11707056B2 (en) | 2013-05-02 | 2023-07-25 | Kymab Limited | Animals, repertoires and methods |
| WO2015017552A1 (en) | 2013-08-01 | 2015-02-05 | Agensys, Inc. | Antibody drug conjugates (adc) that bind to cd37 proteins |
| MX369452B (es) | 2013-08-07 | 2019-11-08 | Regeneron Pharma | Animales no humanos deficientes en lncrna. |
| KR20200103882A (ko) | 2013-09-18 | 2020-09-02 | 리제너론 파마슈티칼스 인코포레이티드 | 히스티딘 엔지니어링된 경쇄 항체 및 그것을 생성하기 위한 유전자 변형된 비-인간 동물 |
| KR102370419B1 (ko) | 2013-09-23 | 2022-03-04 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화된 신호-조절 단백질 유전자를 가지는 비-인간 동물 |
| SG11201602236SA (en) | 2013-10-01 | 2016-04-28 | Kymab Ltd | Animal models and therapeutic molecules |
| EP3430898A1 (en) | 2013-11-19 | 2019-01-23 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized a proliferation-inducing ligand gene |
| WO2015077071A1 (en) | 2013-11-19 | 2015-05-28 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized b-cell activating factor gene |
| PL3080279T3 (pl) | 2013-12-11 | 2019-03-29 | Regeneron Pharmaceuticals, Inc. | Sposoby i kompozycje do celowanej modyfikacji genomu |
| JP6174811B2 (ja) | 2013-12-11 | 2017-08-02 | 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． | ゲノムの標的改変のための方法及び組成物 |
| WO2015108102A1 (ja) | 2014-01-15 | 2015-07-23 | 国立大学法人 群馬大学 | Ａｔｐ可視化動物およびその用途 |
| TWI681969B (zh) * | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對ｐｄ-１的人類抗體 |
| JP6636498B2 (ja) | 2014-03-21 | 2020-01-29 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | 単一ドメイン結合タンパク質を作る非ヒト動物 |
| RU2016141123A (ru) | 2014-03-21 | 2018-04-23 | Регенерон Фармасьютикалз, Инк. | Антигенсвязывающие белки vl, проявляющие различные связывающие характеристики |
| PT3482629T (pt) | 2014-05-19 | 2021-02-18 | Univ Yale | Animais não humanos geneticamente modificados que expressam epo humana |
| ES2877275T3 (es) | 2014-05-30 | 2021-11-16 | Regeneron Pharma | Animales con dipeptidil peptidasa IV (DPP4) humanizada |
| RU2704283C9 (ru) | 2014-06-06 | 2020-02-07 | Регенерон Фармасьютикалз, Инк. | Способы и композиции для модификации целевого локуса |
| BR112016029650A2 (pt) | 2014-06-19 | 2017-10-24 | Regeneron Pharma | roedor, polipeptídeo pd-1, célula isolada ou tecido de roedor, célula-tronco embrionária de roedor, métodos de produzir um roedor, de reduzir o crescimento de tumor em um roedor, de matar células tumorais em um roedor e de avaliar as propriedades farmacocinéticas de uma droga que direciona pd-1 humano, e, modelo de tumor de roedor? |
| CA2953499C (en) | 2014-06-23 | 2023-10-24 | Regeneron Pharmaceuticals, Inc. | Nuclease-mediated dna assembly |
| PT3161128T (pt) * | 2014-06-26 | 2018-11-21 | Regeneron Pharma | Métodos e composições para modificações genéticas alvejadas e métodos de utilização |
| US20160081314A1 (en) | 2014-09-19 | 2016-03-24 | Regeneron Pharmaceuticals, Inc. | Chimeric Antigen Receptors |
| EP3207124B1 (en) | 2014-10-15 | 2019-06-26 | Regeneron Pharmaceuticals, Inc. | Methods and compositions for generating or maintaining pluripotent cells |
| EP3521437B1 (en) | 2014-11-21 | 2025-01-15 | Regeneron Pharmaceuticals, Inc. | Methods for targeted genetic modification using paired guide rnas |
| PL3689140T3 (pl) | 2014-11-24 | 2022-09-05 | Regeneron Pharmaceuticals, Inc. | Zwierzęta inne niż ludzie eksprymujące humanizowany kompleks CD3 |
| IL286403B2 (en) | 2014-12-05 | 2023-10-01 | Regeneron Pharma | Non-human animals possess a humanized CLUSTER OF DIFFERENTIATION 47 gene |
| HUE067123T2 (hu) | 2014-12-09 | 2024-10-28 | Regeneron Pharma | Humanizált differenciációs klaszter 274 génnel rendelkezõ nem humán állatok |
| SG11201704646YA (en) * | 2014-12-19 | 2017-07-28 | Regeneron Pharma | Methods and compositions for targeted genetic modification through single-step multiple targeting |
| SG11201707195SA (en) | 2015-03-09 | 2017-10-30 | Agensys Inc | Antibody drug conjugates (adc) that bind to flt3 proteins |
| KR102616160B1 (ko) | 2015-03-16 | 2023-12-22 | 리제너론 파마슈티칼스 인코포레이티드 | 저하된 상위 및 하위 운동 뉴런 기능 및 감각 지각을 나타내는 비-인간 동물 |
| US11111314B2 (en) | 2015-03-19 | 2021-09-07 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
| CN107666828B (zh) | 2015-04-06 | 2021-04-09 | 瑞泽恩制药公司 | 非人动物中的人源化t细胞介导的免疫应答 |
| US10123518B2 (en) | 2015-04-13 | 2018-11-13 | Regeneron Pharmaceuticals, Inc | Genetically modified non-human animals and methods of use thereof |
| US10395759B2 (en) | 2015-05-18 | 2019-08-27 | Regeneron Pharmaceuticals, Inc. | Methods and systems for copy number variant detection |
| EP3297662A4 (en) | 2015-05-18 | 2019-03-13 | Agensys, Inc. | ANTIBODIES BINDING TO AXL PROTEINS |
| US10787517B2 (en) | 2015-05-18 | 2020-09-29 | Agensys, Inc. | Antibodies that bind to AXL proteins |
| RU2725737C2 (ru) * | 2015-05-29 | 2020-07-03 | Регенерон Фармасьютикалс, Инк. | Животные, отличные от человека, с нарушением в локусе c9orf72 |
| US10412939B2 (en) | 2015-09-02 | 2019-09-17 | Regeneron Pharmaceuticals, Inc. | Rodent model of prostate cancer |
| TW202417497A (zh) | 2015-10-12 | 2024-05-01 | 美商再生元醫藥公司 | 活化瘦素受體的抗原結合蛋白 |
| JP6997708B2 (ja) | 2015-11-20 | 2022-02-04 | 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 | ヒト化されたｌｙｍｐｈｏｃｙｔｅ－ａｃｔｉｖａｔｉｏｎ ｇｅｎｅ ３遺伝子を有する非ヒト動物 |
| DE102016122317A1 (de) * | 2015-11-24 | 2017-05-24 | Glaxosmithkline Intellectual Property Development Limited | Transientes transfektionsverfahren für retrovirale produktion |
| BR112018010635A2 (pt) * | 2015-11-24 | 2018-11-27 | Glaxosmithkline Ip Dev Ltd | linhagens celulares estáveis para a produção retroviral |
| US10813346B2 (en) | 2015-12-03 | 2020-10-27 | Trianni, Inc. | Enhanced immunoglobulin diversity |
| SG11201805973WA (en) | 2016-01-13 | 2018-08-30 | Regeneron Pharma | Rodents having an engineered heavy chain diversity region |
| US20170218398A1 (en) * | 2016-01-30 | 2017-08-03 | Markus Alexander Brown | Method to selectively target cancerous cells for genetic manipulation |
| EP3411476B1 (en) | 2016-02-04 | 2024-04-24 | Trianni, Inc. | Enhanced production of immunoglobulins |
| SG11201806176PA (en) | 2016-02-04 | 2018-08-30 | Regeneron Pharma | Non-human animals having an engineered angptl8 gene |
| KR102465122B1 (ko) | 2016-02-12 | 2022-11-09 | 리제너론 파마슈티칼스 인코포레이티드 | 비정상적인 핵형을 검출하기 위한 방법 및 시스템 |
| RU2018130010A (ru) | 2016-02-16 | 2020-03-17 | Регенерон Фармасьютикалз, Инк. | Животные, отличные от человека, имеющие мутантный ген кинурениназы |
| AU2017228293B2 (en) | 2016-02-29 | 2023-05-25 | Regeneron Pharmaceuticals, Inc. | Rodents having a humanized Tmprss gene |
| AU2017242028A1 (en) | 2016-03-29 | 2018-09-06 | Regeneron Pharmaceuticals, Inc. | Genetic variant-phenotype analysis system and methods of use |
| NZ747857A (en) | 2016-05-20 | 2023-01-27 | Regeneron Pharma | Methods for breaking immunological tolerance using multiple guide rnas |
| RS66700B1 (sr) | 2016-06-03 | 2025-05-30 | Regeneron Pharma | Glodari koji eksprimiraju egzogenu terminalnu dezoksinukleotidil transferazu |
| JP7109007B2 (ja) | 2016-06-27 | 2022-07-29 | ザ・リージエンツ・オブ・ザ・ユニバーシテイー・オブ・カリフオルニア | がん治療の組み合わせ |
| US10912287B2 (en) | 2016-06-28 | 2021-02-09 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd | Genetically modified mice expressing humanized PD-1 |
| SG11201901305YA (en) | 2016-07-29 | 2019-03-28 | Regeneron Pharma | Mice comprising mutations resulting in expression of c-truncated fibrillin-1 |
| CA3038548A1 (en) | 2016-09-30 | 2018-04-05 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a hexanucleotide repeat expansion in a c9orf72 locus |
| DK4082334T3 (da) | 2016-11-04 | 2025-06-02 | Regeneron Pharma | Ikke humane dyr med et modificeret immunglobulin-lambda-letkædelocus |
| KR102777514B1 (ko) | 2017-01-19 | 2025-03-06 | 옴니에이비 오퍼레이션스, 인코포레이티드 | 다중 중쇄 면역글로불린 유전자좌를 갖는 트랜스제닉 설치류 기원의 인간 항체 |
| JP2020508073A (ja) | 2017-02-27 | 2020-03-19 | 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． | 網膜分離症の非ヒト動物モデル |
| BR112020001364A2 (pt) | 2017-07-31 | 2020-08-11 | Regeneron Pharmaceuticals, Inc. | métodos para testar e modificar a capacidade de uma crispr/cas nuclease. |
| WO2019028023A2 (en) | 2017-07-31 | 2019-02-07 | Regeneron Pharmaceuticals, Inc. | METHODS AND COMPOSITIONS FOR EVALUATING CRISPR / CAS MEDIATED DISRUPTION OR EXCISION AND CRISPR / CAS INDUCED RECOMBINATION USING IN VIVO EXOGENIC DONOR NUCLEIC ACID |
| KR20240128129A (ko) | 2017-09-29 | 2024-08-23 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화 C1q 복합체를 발현하는 비인간 동물 |
| EP4276185A3 (en) | 2017-09-29 | 2024-02-21 | Regeneron Pharmaceuticals, Inc. | Rodents comprising a humanized ttr locus and methods of use |
| WO2019072241A1 (en) | 2017-10-13 | 2019-04-18 | Beijing Biocytogen Co., Ltd | NON-HUMAN ANIMAL GENETICALLY MODIFIED WITH PD-1 HUMAN OR CHIMERIC |
| CN109666701B (zh) * | 2017-10-13 | 2021-08-24 | 百奥赛图(北京)医药科技股份有限公司 | 一种pd-1基因修饰人源化动物模型的构建方法及其应用 |
| IL274740B2 (en) | 2017-11-30 | 2024-06-01 | Regeneron Pharma | Non-human animals comprising a humanized trkb locus |
| WO2019113065A1 (en) | 2017-12-05 | 2019-06-13 | Regeneron Pharmaceuticals, Inc. | Non-human animals having an engineered immunoglobulin lambda light chain and uses thereof |
| WO2019183123A1 (en) | 2018-03-19 | 2019-09-26 | Regeneron Pharmaceuticals, Inc. | Transcription modulation in animals using crispr/cas systems |
| CA3093850A1 (en) | 2018-03-26 | 2019-10-03 | Regeneron Pharmaceuticals, Inc. | Humanized rodents for testing therapeutic agents |
| EP4596043A3 (en) | 2018-04-06 | 2025-10-01 | Regeneron Pharmaceuticals, Inc. | A leptin receptor agonist antibody for use in increasing bone mass in a subject suffering from metabolic dysfunction or hypoleptinemia |
| JP2021525927A (ja) | 2018-06-01 | 2021-09-27 | リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | スパースベクトルベースのマトリクス変換のための方法およびシステム |
| IL318469A (en) | 2018-06-14 | 2025-03-01 | Regeneron Pharma | Non-human animals capable of reorganizing transgenic DH-DH, and their uses |
| FI3823443T3 (fi) | 2018-07-16 | 2024-07-25 | Regeneron Pharma | Ditra-taudin jyrsijämallit ja niiden käyttö |
| CN109504708A (zh) * | 2018-12-03 | 2019-03-22 | 江苏集萃药康生物科技有限公司 | 一种筛选标记自我删除的基因打靶载体及方法 |
| CA3120799A1 (en) | 2018-12-20 | 2020-06-25 | Regeneron Pharmaceuticals, Inc. | Nuclease-mediated repeat expansion |
| US20220104468A1 (en) | 2019-01-22 | 2022-04-07 | St. Jude Children's Research Hospital | Modulation of lc3-associated endocytosis pathway and genetically modified non-human animals as a model of neuroinflammation and neurodegeneration |
| CA3125380A1 (en) | 2019-02-18 | 2020-08-27 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | Genetically modified non-human animals with humanized immunoglobulin locus |
| SG11202107589PA (en) | 2019-02-22 | 2021-08-30 | Regeneron Pharma | Rodents having genetically modified sodium channels and methods of use thereof |
| IL286905B2 (en) | 2019-04-04 | 2024-06-01 | Regeneron Pharma | Non-human animals containing the human coagulation factor 12 locus |
| CA3133359C (en) | 2019-04-04 | 2023-04-11 | Regeneron Pharmaceuticals, Inc. | Methods for scarless introduction of targeted modifications into targeting vectors |
| EP3955957A1 (en) | 2019-04-15 | 2022-02-23 | Qwixel Therapeutics LLC | Fusion protein composition(s) comprising targeted masked type i interferons (ifna and ifnb) and an antibody against tumor antigen, for use in the treatment of cancer |
| US11891618B2 (en) | 2019-06-04 | 2024-02-06 | Regeneron Pharmaceuticals, Inc. | Mouse comprising a humanized TTR locus with a beta-slip mutation and methods of use |
| US20220330532A1 (en) | 2019-06-05 | 2022-10-20 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a limited lambda light chain repertoire expressed from the kappa locus and uses thereof |
| US11622547B2 (en) | 2019-06-07 | 2023-04-11 | Regeneran Pharmaceuticals, Inc. | Genetically modified mouse that expresses human albumin |
| JP7706380B2 (ja) | 2019-06-27 | 2025-07-11 | 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 | Ｔｄｐ－４３タンパク症のモデル化 |
| CA3145453A1 (en) | 2019-07-01 | 2021-01-07 | Tonix Pharma Limited | Anti-cd154 antibodies and uses thereof |
| MX2022003935A (es) | 2019-10-04 | 2022-04-25 | Tae Life Sciences Llc | Composiciones de anticuerpo que comprenden mutaciones fc y propiedades de conjugacion especificas del sitio. |
| WO2021108363A1 (en) | 2019-11-25 | 2021-06-03 | Regeneron Pharmaceuticals, Inc. | Crispr/cas-mediated upregulation of humanized ttr allele |
| CN115175559A (zh) | 2020-01-28 | 2022-10-11 | 瑞泽恩制药公司 | 包含人源化pnpla3基因座的非人动物及其使用方法 |
| WO2021158883A1 (en) | 2020-02-07 | 2021-08-12 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized klkb1 locus and methods of use |
| US20230102342A1 (en) | 2020-03-23 | 2023-03-30 | Regeneron Pharmaceuticals, Inc. | Non-human animals comprising a humanized ttr locus comprising a v30m mutation and methods of use |
| CN116075221A (zh) | 2020-04-21 | 2023-05-05 | 瑞泽恩制药公司 | 具有人源化cxcl13基因的非人动物 |
| IL298632A (en) | 2020-06-02 | 2023-01-01 | Biocytogen Pharmaceuticals Beijing Co Ltd | Non-human animals genetically modified with a common light chain immunoglobulin locus |
| RU2751237C1 (ru) * | 2020-06-10 | 2021-07-12 | Регенерон Фармасьютикалс, Инк. | Способы и композиции для направленной модификации генома |
| JP2023541216A (ja) | 2020-06-25 | 2023-09-29 | ヒューマブ カンパニー リミテッド | ヘテロ接合型トランスジェニック動物 |
| TW202229328A (zh) | 2020-09-11 | 2022-08-01 | 美商再生元醫藥公司 | 抗原特異性抗體之鑑定及產生 |
| EP4221496A1 (en) | 2020-10-01 | 2023-08-09 | Regeneron Pharmaceuticals, Inc. | Rodent animals expressing human cr1 |
| US12012441B2 (en) | 2020-10-26 | 2024-06-18 | Neptune Biosciences Llc | Engineered human IL-21 cytokines and methods for using the same |
| JP2024500399A (ja) | 2020-12-16 | 2024-01-09 | 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Ｆｃアルファ受容体を発現するマウス |
| KR20230124973A (ko) | 2020-12-21 | 2023-08-28 | 리제너론 파마슈티칼스 인코포레이티드 | 인간화 tslp 유전자, 인간화 tslp 수용체 유전자, 및/또는인간화 il7ra 유전자를 갖는 비인간 동물 |
| US12371475B2 (en) | 2020-12-23 | 2025-07-29 | Regeneron Pharmaceuticals, Inc. | Nucleic acids encoding anchor modified antibodies and uses thereof |
| CN116963750A (zh) | 2021-01-06 | 2023-10-27 | 通尼克斯制药有限公司 | 用经修饰的抗-cd154抗体诱导免疫耐受的方法 |
| JP2024512702A (ja) | 2021-03-31 | 2024-03-19 | 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 | Ｔｃｒβレパートリーの改善された多様性を伴うヒト化細胞免疫系の構成要素を含む、遺伝的に改変されたマウス |
| US20240199725A1 (en) | 2021-04-16 | 2024-06-20 | Korea University Research And Business Foundation | Human antibody targeting covid-19 virus |
| AU2022292462A1 (en) | 2021-06-18 | 2023-12-07 | Nammi Therapeutics, Inc. | FUSION PROTEIN COMPOSITION(S) COMPRISING MASKED TYPE I INTERFERONS (IFNα AND IFNβ) FOR USE IN THE TREATMENT OF CANCER AND METHODS THEREOF |
| US20240415980A1 (en) | 2021-10-28 | 2024-12-19 | Regeneron Pharmaceuticals, Inc. | Crispr/cas-related methods and compositions for knocking out c5 |
| WO2023108047A1 (en) | 2021-12-08 | 2023-06-15 | Regeneron Pharmaceuticals, Inc. | 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 |
| WO2023150798A1 (en) | 2022-02-07 | 2023-08-10 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for defining optimal treatment timeframes in lysosomal disease |
| AU2023218391A1 (en) | 2022-02-11 | 2024-07-11 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for screening 4r tau targeting agents |
| WO2023212560A1 (en) | 2022-04-26 | 2023-11-02 | Regeneron Pharmaceuticals, Inc. | A rodent model of fibrodysplasia ossificans progressiva |
| WO2023235677A1 (en) | 2022-05-31 | 2023-12-07 | Regeneron Pharmaceuticals, Inc. | Animal model of tdp-43 proteinopathy |
| WO2023235725A2 (en) | 2022-05-31 | 2023-12-07 | Regeneron Pharmaceuticals, Inc. | Crispr-based therapeutics for c9orf72 repeat expansion disease |
| US20230417899A1 (en) | 2022-06-27 | 2023-12-28 | Oshkosh Corporation | Position tracking for a lift device |
| US20240102045A1 (en) | 2022-07-19 | 2024-03-28 | Regeneron Pharmaceuticals, Inc. | Vectors, genetically modified cells, and genetically modified non-human animals comprising the same |
| KR20250077529A (ko) | 2022-09-22 | 2025-05-30 | 리제너론 파아마슈티컬스, 인크. | 인간 세포 면역계의 성분을 발현하는, 유전자적으로 변형된 마우스 |
| EP4593590A1 (en) | 2022-09-29 | 2025-08-06 | Regeneron Pharmaceuticals, Inc. | Correction of hepatosteatosis in humanized liver animals through restoration of il6/il6r/gp130 signaling in human hepatocytes |
| KR20250144399A (ko) | 2023-02-01 | 2025-10-10 | 리제너론 파마슈티칼스 인코포레이티드 | 변형된 klhdc7b 유전자좌를 포함하는 동물 |
| WO2024258743A1 (en) | 2023-06-13 | 2024-12-19 | Adcentrx Therapeutics, Inc. | Methods and compositions related to antibodies and antibody drug conjugates (adcs) that bind nectin-4 proteins |
| AU2024304358A1 (en) | 2023-06-16 | 2025-11-06 | Regeneron Pharmaceuticals, Inc. | Vectors, genetically modified cells, and genetically modified non-human animals comprising the same |
| WO2025122669A1 (en) | 2023-12-05 | 2025-06-12 | Regeneron Pharmaceuticals, Inc. | Non-human animals having a humanized complement factor b gene |
| WO2025171307A1 (en) | 2024-02-08 | 2025-08-14 | Regeneron Pharmaceuticals, Inc. | Vectors, genetically modified cells, and genetically modified non-human animals comprising the same |
| WO2025212991A1 (en) | 2024-04-05 | 2025-10-09 | Regeneron Pharmaceuticals, Inc. | Rodent models of disease |
| WO2025235388A1 (en) | 2024-05-06 | 2025-11-13 | Regeneron Pharmaceuticals, Inc. | Transgene genomic identification by nuclease-mediated long read sequencing |
| WO2025250495A1 (en) | 2024-05-28 | 2025-12-04 | Regeneron Pharmaceuticals, Inc. | Acceleration of human hepatocyte engraftment in humanized liver animals by supplementing paracrine ligands or agonists that activate human liver regeneration signals |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5770429A (en) * | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| WO1993004169A1 (en) | 1991-08-20 | 1993-03-04 | Genpharm International, Inc. | Gene targeting in animal cells using isogenic dna constructs |
| NZ255101A (en) * | 1992-07-24 | 1997-08-22 | Cell Genesys Inc | A yeast artificial chromosome (yac) vector containing an hprt minigene expressible in murine stem cells and genetically modified rodent therefor |
| DE4228162C1 (de) * | 1992-08-25 | 1994-01-13 | Rajewsky Klaus Dr | Verfahren zum Ersetzen homologer Genabschnitte aus Säugern in der Keimbahn von nicht-menschlichen Säugern |
| US5436149A (en) | 1993-02-19 | 1995-07-25 | Barnes; Wayne M. | Thermostable DNA polymerase with enhanced thermostability and enhanced length and efficiency of primer extension |
| AU6819494A (en) * | 1993-04-26 | 1994-11-21 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| WO2000046251A2 (en) * | 1999-02-05 | 2000-08-10 | Buelow Jens Ulrich | Human polyclonal antibodies from transgenic nonhuman animals |
| US6586251B2 (en) * | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
-
2000
- 2000-12-07 US US09/732,234 patent/US6586251B2/en not_active Expired - Lifetime
-
2001
- 2001-10-31 CZ CZ2003-1197A patent/CZ304856B6/cs not_active IP Right Cessation
- 2001-10-31 RU RU2003116125/13A patent/RU2290441C2/ru active
- 2001-10-31 NZ NZ525511A patent/NZ525511A/en not_active IP Right Cessation
- 2001-10-31 BR BRPI0115096A patent/BRPI0115096B1/pt active IP Right Grant
- 2001-10-31 AT AT01992495T patent/ATE332388T1/de not_active IP Right Cessation
- 2001-10-31 CA CA2426398A patent/CA2426398C/en not_active Expired - Lifetime
- 2001-10-31 AU AU2002220048A patent/AU2002220048B2/en not_active Expired
- 2001-10-31 DE DE60121372T patent/DE60121372T2/de not_active Expired - Lifetime
- 2001-10-31 HU HU0301575A patent/HU227639B1/hu unknown
- 2001-10-31 KR KR1020037005885A patent/KR100833136B1/ko not_active Expired - Lifetime
- 2001-10-31 EP EP01992495A patent/EP1399575B1/en not_active Expired - Lifetime
- 2001-10-31 AU AU2004802A patent/AU2004802A/xx active Pending
- 2001-10-31 MX MXPA03003797A patent/MXPA03003797A/es active IP Right Grant
- 2001-10-31 CN CNB018216609A patent/CN100497642C/zh not_active Expired - Lifetime
- 2001-10-31 PL PL361927A patent/PL204759B1/pl unknown
- 2001-10-31 WO PCT/US2001/045375 patent/WO2002036789A2/en not_active Ceased
- 2001-10-31 JP JP2002539535A patent/JP5339566B2/ja not_active Expired - Lifetime
-
2003
- 2003-04-28 NO NO20031897A patent/NO332300B1/no not_active IP Right Cessation
-
2010
- 2010-06-15 JP JP2010136321A patent/JP2010220628A/ja active Pending
-
2013
- 2013-05-23 JP JP2013108631A patent/JP5892975B2/ja not_active Expired - Lifetime
- 2013-11-29 JP JP2013247817A patent/JP5945263B2/ja not_active Expired - Lifetime
-
2014
- 2014-12-26 JP JP2014265082A patent/JP2015062432A/ja not_active Withdrawn
-
2017
- 2017-02-14 JP JP2017024803A patent/JP6486979B2/ja not_active Expired - Lifetime
- 2017-02-14 JP JP2017024802A patent/JP2017123855A/ja not_active Withdrawn
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2426398C (en) | Methods of modifying eukaryotic cells | |
| US10344299B2 (en) | Compositions and methods for modifying cells | |
| AU2002220048A1 (en) | Methods of modifying eukaryotic cells | |
| DK2264163T3 (en) | Methods for the modification of eukaryotic cells | |
| IL155580A (en) | Ex vivo method for modifying endogenous gene or chromosomal locus in eukaryotic cells | |
| HK1059802B (en) | Methods of modifying eukaryotic cells | |
| HK1228448B (en) | Method of modifying eukaryotic cells |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKEX | Expiry |
Effective date: 20211101 |
|
| MKEX | Expiry |
Effective date: 20211101 |