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 journalArticle

496 Scopus citations

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).

Original languageEnglish (US)
Pages (from-to)326-328
Number of pages3
JournalNature Methods
Volume12
Issue number4
DOIs
StatePublished - Mar 31 2015

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Chavez, A., Scheiman, J., Vora, S., Pruitt, B. W., Tuttle, M., P R Iyer, E., Lin, S., Kiani, S., Guzman, C. D., Wiegand, D. J., Ter-Ovanesyan, D., Braff, J. L., Davidsohn, N., Housden, B. E., Perrimon, N., Weiss, R., Aach, J., Collins, J. J., & Church, G. M. (2015). Highly efficient Cas9-mediated transcriptional programming. Nature Methods, 12(4), 326-328. https://doi.org/10.1038/nmeth.3312