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dc.contributor.authorWang, Haoyi
dc.contributor.authorYang, Hui
dc.contributor.authorShi, Linyu
dc.contributor.authorKatz, Yarden
dc.contributor.authorTheunissen, Thorold W
dc.contributor.authorRangarajan, Sudharshan
dc.contributor.authorJaenisch, Rudolf
dc.contributor.authorShivalila, Chikdu Shakti
dc.contributor.authorDadon, Daniel Benjamin
dc.contributor.authorCheng, Albert Wu
dc.date.accessioned2014-01-31T19:44:23Z
dc.date.available2014-01-31T19:44:23Z
dc.date.issued2013-08
dc.date.submitted2013-08
dc.identifier.issn1001-0602
dc.identifier.issn1748-7838
dc.identifier.urihttp://hdl.handle.net/1721.1/84630
dc.description.abstractTechnologies allowing for specific regulation of endogenous genes are valuable for the study of gene functions and have great potential in therapeutics. We created the CRISPR-on system, a two-component transcriptional activator consisting of a nuclease-dead Cas9 (dCas9) protein fused with a transcriptional activation domain and single guide RNAs (sgRNAs) with complementary sequence to gene promoters. We demonstrate that CRISPR-on can efficiently activate exogenous reporter genes in both human and mouse cells in a tunable manner. In addition, we show that robust reporter gene activation in vivo can be achieved by injecting the system components into mouse zygotes. Furthermore, we show that CRISPR-on can activate the endogenous IL1RN, SOX2, and OCT4 genes. The most efficient gene activation was achieved by clusters of 3-4 sgRNAs binding to the proximal promoters, suggesting their synergistic action in gene induction. Significantly, when sgRNAs targeting multiple genes were simultaneously introduced into cells, robust multiplexed endogenous gene activation was achieved. Genome-wide expression profiling demonstrated high specificity of the system.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant HD 045022)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant R37CA084198)en_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/cr.2013.122en_US
dc.rightsCreative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en_US
dc.sourceCell Researchen_US
dc.titleMultiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator systemen_US
dc.typeArticleen_US
dc.identifier.citationCheng, Albert W, Haoyi Wang, Hui Yang, Linyu Shi, Yarden Katz, Thorold W Theunissen, Sudharshan Rangarajan, Chikdu S Shivalila, Daniel B Dadon, and Rudolf Jaenisch. “Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system.” Cell Research 23, no. 10 (August 27, 2013): 1163-1171. © 2013 IBCB, SIBS, CASen_US
dc.contributor.departmentMassachusetts Institute of Technology. Computational and Systems Biology Programen_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.departmentWhitehead Institute for Biomedical Researchen_US
dc.contributor.mitauthorCheng, Albert W.en_US
dc.contributor.mitauthorKatz, Yardenen_US
dc.contributor.mitauthorShivalila, Chikdu Shaktien_US
dc.contributor.mitauthorDadon, Daniel Benjaminen_US
dc.contributor.mitauthorJaenisch, Rudolfen_US
dc.relation.journalCell Researchen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsCheng, Albert W; Wang, Haoyi; Yang, Hui; Shi, Linyu; Katz, Yarden; Theunissen, Thorold W; Rangarajan, Sudharshan; Shivalila, Chikdu S; Dadon, Daniel B; Jaenisch, Rudolfen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-7256-3158
dc.identifier.orcidhttps://orcid.org/0000-0002-2905-0306
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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