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dc.contributor.authorWang, Haoyi
dc.contributor.authorYang, Hui
dc.contributor.authorShivalila, Chikdu Shakti
dc.contributor.authorDawlaty, Meelad M.
dc.contributor.authorCheng, Albert W.
dc.contributor.authorZhang, Feng
dc.contributor.authorJaenisch, Rudolf
dc.date.accessioned2016-06-01T20:53:40Z
dc.date.available2016-06-01T20:53:40Z
dc.date.issued2013-05
dc.date.submitted2013-04
dc.identifier.issn00928674
dc.identifier.issn1097-4172
dc.identifier.urihttp://hdl.handle.net/1721.1/102794
dc.description.abstractMice carrying mutations in multiple genes are traditionally generated by sequential recombination in embryonic stem cells and/or time-consuming intercrossing of mice with a single mutation. The CRISPR/Cas system has been adapted as an efficient gene-targeting technology with the potential for multiplexed genome editing. We demonstrate that CRISPR/Cas-mediated gene editing allows the simultaneous disruption of five genes (Tet1, 2, 3, Sry, Uty - 8 alleles) in mouse embryonic stem (ES) cells with high efficiency. Coinjection of Cas9 mRNA and single-guide RNAs (sgRNAs) targeting Tet1 and Tet2 into zygotes generated mice with biallelic mutations in both genes with an efficiency of 80%. Finally, we show that coinjection of Cas9 mRNA/sgRNAs with mutant oligos generated precise point mutations simultaneously in two target genes. Thus, the CRISPR/Cas system allows the one-step generation of animals carrying mutations in multiple genes, an approach that will greatly accelerate the in vivo study of functionally redundant genes and of epistatic gene interactions.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH grant R37-HD045022)en_US
dc.language.isoen_US
dc.publisherCell Press/Elsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.cell.2013.04.025en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleOne-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineeringen_US
dc.typeArticleen_US
dc.identifier.citationWang, Haoyi, Hui Yang, Chikdu S. Shivalila, Meelad M. Dawlaty, Albert W. Cheng, Feng Zhang, and Rudolf Jaenisch. “One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering.” Cell 153, no. 4 (May 2013): 910–918.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Computational and Systems Biology Programen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.departmentMcGovern Institute for Brain Research at MITen_US
dc.contributor.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.mitauthorShivalila, Chikdu Shaktien_US
dc.contributor.mitauthorCheng, Albert W.en_US
dc.contributor.mitauthorZhang, Fengen_US
dc.contributor.mitauthorJaenisch, Rudolfen_US
dc.relation.journalCellen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsWang, Haoyi; Yang, Hui; Shivalila, Chikdu S.; Dawlaty, Meelad M.; Cheng, Albert W.; Zhang, Feng; Jaenisch, Rudolfen_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0003-2782-2509
dc.identifier.orcidhttps://orcid.org/0000-0002-2905-0306
mit.licensePUBLISHER_CCen_US


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