Transcription Activator-Like Effector Hybrids for Conditional Control and Rewiring of Chromosomal Transgene Expression

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dc.contributor.ISNI0000 0001 2535 9739 (Bleris, L)
dc.contributor.LCNA2012076942‏ (Bleris, L)
dc.contributor.authorLi, Yien_US
dc.contributor.authorMoore, Richarden_US
dc.contributor.authorGuinn, Michaelen_US
dc.contributor.authorBleris, Leonidasen_US
dc.contributor.sponsorErik Jonsson School of Engineering and Computer Science. Center for Systems Biology.en_US
dc.date.accessioned2013-10-10T21:36:06Z
dc.date.available2013-10-10T21:36:06Z
dc.date.created2012-11-28
dc.description.abstractThe ability to conditionally rewire pathways in human cells holds great therapeutic potential. Transcription activator-like effectors (TALEs) are a class of naturally occurring specific DNA binding proteins that can be used to introduce targeted genome modifications or control gene expression. Here we present TALE hybrids engineered to respond to endogenous signals and capable of controlling transgenes by applying a predetermined and tunable action at the single-cell level. Specifically, we first demonstrate that combinations of TALEs can be used to modulate the expression of stably integrated genes in kidney cells. We then introduce a general purpose two-hybrid approach that can be customized to regulate the function of any TALE either using effector molecules or a heterodimerization reaction. Finally, we demonstrate the successful interface of TALEs to specific endogenous signals, namely hypoxia signaling and microRNAs, essentially closing the loop between cellular information and chromosomal transgene expression. © 2012 Macmillan Publishers Limited. All rights reserved.en_US
dc.identifier.bibliographicCitationLi, Y., R. Moore, M. Guinn, and L. Bleris. 2012. "Transcription activator-like effector hybrids for conditional control and rewiring of chromosomal transgene expression." Scientific Reports 2: 897.
dc.identifier.issn2045-2322en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/2892
dc.identifier.volume2en_US
dc.relation.urihttp://dx.doi.org/10.1038/srep00897en_US
dc.rightsCC BY-NC-ND 3.0 (Attribution-NonCommercial-NoDerivatives)en_US
dc.rights©2012 The Authorsen_US
dc.source.journalScientific Reportsen_US
dc.subjectProtein engineeringen_US
dc.subjectHypoxia-Inducible Factor 1, alphaen_US
dc.subjectMicroRNAsen_US
dc.titleTranscription Activator-Like Effector Hybrids for Conditional Control and Rewiring of Chromosomal Transgene Expressionen_US
dc.typetexten_US
dc.type.genrearticleen_US

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