Highly efficient Cas9-mediated transcriptional programming.
Publication information:
Chavez A, Scheiman J, Vora S, Pruitt B, Tuttle M, P R Iyer E, Lin S, Kiani S, Guzman C, Wiegand D, Ter-Ovanesyan D, Braff J, Davidsohn N, Housden B, Perrimon N, Weiss R, Aach J, Collins J, Church G. Highly efficient Cas9-mediated transcriptional programming.
Nat Methods. 2015;12(4):326–8. PMID: 25730490
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).