TY - JOUR T1 - Highly-efficient Cas9-mediated transcriptional programming JF - bioRxiv DO - 10.1101/012880 SP - 012880 AU - Alejandro Chavez AU - Jonathan Scheiman AU - Suhani Vora AU - Benjamin W. Pruitt AU - Marcelle Tuttle AU - Eswar Iyer AU - Samira Kiani AU - Christopher D. Guzman AU - Daniel J. Wiegand AU - Dimtry Ter-Ovanesyan AU - Jonathan L. Braff AU - Noah Davidsohn AU - Ron Weiss AU - John Aach AU - James J. Collins AU - George M. Church Y1 - 2014/01/01 UR - http://biorxiv.org/content/early/2014/12/20/012880.abstract N2 - 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). ER -