(12a) Transcription Activator-Like Effector Hybrids for Conditional Control and Rewiring of Chromosomal Transgene Expression

Moore, R., The University of Texas at Dallas
Li, Y., The University of Texas at Dallas
Bleris, L., The University of Texas at Dallas

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 (1) 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.

  1. Yi Li, Richard Moore, Michael Guinn, Leonidas Bleris. Transcription activator-like effector hybrids for conditional control and rewiring of chromosomal transgene expression. Sci Rep. 2012;2:897. doi: 10.1038/srep00897. Epub 2012 Nov 28.