%0 Journal Article %J Nat Methods %D 2015 %T Highly efficient Cas9-mediated transcriptional programming. %A Chavez, Alejandro %A Scheiman, Jonathan %A Vora, Suhani %A Pruitt, Benjamin W %A Tuttle, Marcelle %A P R Iyer, Eswar %A Lin, Shuailiang %A Kiani, Samira %A Guzman, Christopher D %A Wiegand, Daniel J %A Ter-Ovanesyan, Dmitry %A Braff, Jonathan L %A Davidsohn, Noah %A Housden, Benjamin E %A Perrimon, Norbert %A Weiss, Ron %A Aach, John %A Collins, James J %A Church, George M %K Cell Differentiation %K Endonucleases %K Genetic Techniques %K HEK293 Cells %K Humans %K Induced Pluripotent Stem Cells %K Neurons %K RNA, Guide %K Staphylococcus aureus %K Transcriptional Activation %X

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).

%B Nat Methods %V 12 %P 326-8 %8 2015 Apr %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/25730490?dopt=Abstract %R 10.1038/nmeth.3312