Highly efficient Cas9-mediated transcriptional programming

Alejandro Chavez, Jonathan Scheiman, Suhani Vora, Benjamin W. Pruitt, Marcelle Tuttle, Eswar P R Iyer, Shuailiang Lin, Samira Kiani, Christopher D. Guzman, Daniel J. Wiegand, Dmitry Ter-Ovanesyan, Jonathan L. Braff, Noah Davidsohn, Benjamin E. Housden, Norbert Perrimon, Ron Weiss, John Aach, James J. Collins, George M. Church

Research output: Contribution to journalArticlepeer-review

1070 Scopus citations


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).

Original languageEnglish (US)
Pages (from-to)326-328
Number of pages3
JournalNature Methods
Issue number4
StatePublished - Mar 31 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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