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dc.contributor.authorZhang, Feng
dc.contributor.authorCong, Le
dc.contributor.authorLodato, Simona
dc.contributor.authorKosuri, Sriram
dc.contributor.authorChurch, George M.
dc.contributor.authorArlotta, Paola
dc.date.accessioned2013-01-31T20:29:39Z
dc.date.available2013-01-31T20:29:39Z
dc.date.issued2011-01
dc.date.submitted2010-11
dc.identifier.issn1087-0156
dc.identifier.issn1546-1696
dc.identifier.urihttp://hdl.handle.net/1721.1/76706
dc.description.abstractThe ability to direct functional proteins to specific DNA sequences is a long-sought goal in the study and engineering of biological processes. Transcription activator–like effectors (TALEs) from Xanthomonas sp. are site-specific DNA-binding proteins that can be readily designed to target new sequences. Because TALEs contain a large number of repeat domains, it can be difficult to synthesize new variants. Here we describe a method that overcomes this problem. We leverage codon degeneracy and type IIs restriction enzymes to generate orthogonal ligation linkers between individual repeat monomers, thus allowing full-length, customized, repeat domains to be constructed by hierarchical ligation. We synthesized 17 TALEs that are customized to recognize specific DNA-binding sites, and demonstrate that they can specifically modulate transcription of endogenous genes (SOX2 and KLF4) in human cells.en_US
dc.description.sponsorshipHarvard University. Society of Fellowsen_US
dc.description.sponsorshipNational Human Genome Research Institute (U.S.) (Center for Excellence in Genomics Science P50 HG003170)en_US
dc.description.sponsorshipUnited States. Dept. of Energy (Genomes to Life DE-FG02-02ER63445)en_US
dc.description.sponsorshipUnited States. Defense Advanced Research Projects Agency (W911NF-08-1-0254, G.M.C.)en_US
dc.description.sponsorshipWyss Institute of Biologically Inspired Engineeringen_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Transformative R01 (R01 NS073124-01))en_US
dc.description.sponsorshipEuropean School of Molecular Medicine (predoctoral fellowship)en_US
dc.language.isoen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofhttp://dx.doi.org/10.1038/nbt.1775en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alike 3.0en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en_US
dc.sourceZhang via Courtney Crummetten_US
dc.titleProgrammable Sequence-Specific Transcriptional Regulation of Mammalian Genome Using Designer TAL Effectorsen_US
dc.typeArticleen_US
dc.identifier.citationZhang, Feng et al. “Efficient Construction of Sequence-specific TAL Effectors for Modulating Mammalian Transcription.” Nature Biotechnology 29.2 (2011): 149–153. Web.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.approverZhang, Feng
dc.contributor.mitauthorZhang, Feng
dc.relation.journalNature Biotechnologyen_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.orderedauthorsZhang, Feng; Cong, Le; Lodato, Simona; Kosuri, Sriram; Church, George M; Arlotta, Paolaen
dc.identifier.orcidhttps://orcid.org/0000-0003-2782-2509
mit.licenseOPEN_ACCESS_POLICYen_US


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