Transcription activator-like effector hybrids for conditional control and rewiring of chromosomal transgene expression.

Transcription activator-like effector hybrids for conditional control and rewiring of chromosomal transgene expression.
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DOI:
10.1038/srep00897
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发表时间:
2012
期刊:
影响因子:
4.6
通讯作者:
Bleris, Leonidas
Bleris, Leonidas
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li, Yi;Moore, Richard;Guinn, Michael;Bleris, Leonidas

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The 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.
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