Highly efficient Cas9-mediated transcriptional programming.

Chavez, Alejandro; Scheiman, Jonathan; Vora, Suhani; Pruitt, Benjamin W; Tuttle, Marcelle; P R Iyer, Eswar; Lin, Shuailiang; Kiani, Samira et al. · Nat Methods · 2015

basic_science · Level V

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Abstract

The RNA-guided nuclease Cas9 can be reengineered as a programmable transcription factor. However, modest levels of gene activation have limited potential applications. We describe an improved transcriptional regulator obtained through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to nuclease-null Cas9. We demonstrate its utility in activating endogenous coding and noncoding genes, targeting several genes simultaneously and stimulating neuronal differentiation of human induced pluripotent stem cells (iPSCs).

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