RT Journal Article SR Electronic T1 Highly-efficient Cas9-mediated transcriptional programming JF bioRxiv FD Cold Spring Harbor Laboratory SP 012880 DO 10.1101/012880 A1 Alejandro Chavez A1 Jonathan Scheiman A1 Suhani Vora A1 Benjamin W. Pruitt A1 Marcelle Tuttle A1 Eswar Iyer A1 Samira Kiani A1 Christopher D. Guzman A1 Daniel J. Wiegand A1 Dimtry Ter-Ovanesyan A1 Jonathan L. Braff A1 Noah Davidsohn A1 Ron Weiss A1 John Aach A1 James J. Collins A1 George M. Church YR 2014 UL http://biorxiv.org/content/early/2014/12/20/012880.abstract AB The RNA-guided bacterial nuclease Cas9 can be reengineered as a programmable transcription factor by a series of changes to the Cas9 protein in addition to the fusion of a transcriptional activation domain (AD)1–5. However, the modest levels of gene activation achieved by current Cas9 activators have limited their potential applications. Here we describe the development of an improved transcriptional regulator through the rational design of a tripartite activator, VP64-p65-Rta (VPR), fused to Cas9. We demonstrate its utility in activating expression of endogenous coding and non-coding genes, targeting several genes simultaneously and stimulating neuronal differentiation of induced pluripotent stem cells (iPSCs).