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

363 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Induced Pluripotent Stem Cells
Gene Targeting
Ribonucleases
Transcriptional Activation
Transcription Factors
Genes
Stem cells
Chemical activation

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology
  • Biochemistry
  • Cell Biology

Cite this

Chavez, A., Scheiman, J., Vora, S., Pruitt, B. W., Tuttle, M., P R Iyer, E., ... Church, G. M. (2015). Highly efficient Cas9-mediated transcriptional programming. Nature Methods, 12(4), 326-328. https://doi.org/10.1038/nmeth.3312

Highly efficient Cas9-mediated transcriptional programming. / Chavez, Alejandro; Scheiman, Jonathan; Vora, Suhani; Pruitt, Benjamin W.; Tuttle, Marcelle; P R Iyer, Eswar; Lin, Shuailiang; Kiani, Samira; Guzman, Christopher D.; Wiegand, Daniel J.; Ter-Ovanesyan, Dmitry; Braff, Jonathan L.; Davidsohn, Noah; Housden, Benjamin E.; Perrimon, Norbert; Weiss, Ron; Aach, John; Collins, James J.; Church, George M.

In: Nature Methods, Vol. 12, No. 4, 31.03.2015, p. 326-328.

Research output: Contribution to journalArticle

Chavez, A, Scheiman, J, Vora, S, Pruitt, BW, Tuttle, M, P R Iyer, E, Lin, S, Kiani, S, Guzman, CD, Wiegand, DJ, Ter-Ovanesyan, D, Braff, JL, Davidsohn, N, Housden, BE, Perrimon, N, Weiss, R, Aach, J, Collins, JJ & Church, GM 2015, 'Highly efficient Cas9-mediated transcriptional programming', Nature Methods, vol. 12, no. 4, pp. 326-328. https://doi.org/10.1038/nmeth.3312
Chavez A, Scheiman J, Vora S, Pruitt BW, Tuttle M, P R Iyer E et al. Highly efficient Cas9-mediated transcriptional programming. Nature Methods. 2015 Mar 31;12(4):326-328. https://doi.org/10.1038/nmeth.3312
Chavez, Alejandro ; Scheiman, Jonathan ; Vora, Suhani ; Pruitt, Benjamin W. ; Tuttle, Marcelle ; P R Iyer, Eswar ; Lin, Shuailiang ; Kiani, Samira ; Guzman, Christopher D. ; Wiegand, Daniel J. ; Ter-Ovanesyan, Dmitry ; Braff, Jonathan L. ; Davidsohn, Noah ; Housden, Benjamin E. ; Perrimon, Norbert ; Weiss, Ron ; Aach, John ; Collins, James J. ; Church, George M. / Highly efficient Cas9-mediated transcriptional programming. In: Nature Methods. 2015 ; Vol. 12, No. 4. pp. 326-328.
@article{bdc8c83ea2534bc99ca48427bd9b741e,
title = "Highly efficient Cas9-mediated transcriptional programming",
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).",
author = "Alejandro Chavez and Jonathan Scheiman and Suhani Vora and Pruitt, {Benjamin W.} and Marcelle Tuttle and {P R Iyer}, Eswar and Shuailiang Lin and Samira Kiani and Guzman, {Christopher D.} and Wiegand, {Daniel J.} and Dmitry Ter-Ovanesyan and Braff, {Jonathan L.} and Noah Davidsohn and Housden, {Benjamin E.} and Norbert Perrimon and Ron Weiss and John Aach and Collins, {James J.} and Church, {George M.}",
year = "2015",
month = "3",
day = "31",
doi = "10.1038/nmeth.3312",
language = "English (US)",
volume = "12",
pages = "326--328",
journal = "Nature Methods",
issn = "1548-7091",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Highly efficient Cas9-mediated transcriptional programming

AU - Chavez, Alejandro

AU - Scheiman, Jonathan

AU - Vora, Suhani

AU - Pruitt, Benjamin W.

AU - Tuttle, Marcelle

AU - P R Iyer, Eswar

AU - Lin, Shuailiang

AU - Kiani, Samira

AU - Guzman, Christopher D.

AU - Wiegand, Daniel J.

AU - Ter-Ovanesyan, Dmitry

AU - Braff, Jonathan L.

AU - Davidsohn, Noah

AU - Housden, Benjamin E.

AU - Perrimon, Norbert

AU - Weiss, Ron

AU - Aach, John

AU - Collins, James J.

AU - Church, George M.

PY - 2015/3/31

Y1 - 2015/3/31

N2 - 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).

AB - 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).

UR - http://www.scopus.com/inward/record.url?scp=84926521955&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84926521955&partnerID=8YFLogxK

U2 - 10.1038/nmeth.3312

DO - 10.1038/nmeth.3312

M3 - Article

VL - 12

SP - 326

EP - 328

JO - Nature Methods

JF - Nature Methods

SN - 1548-7091

IS - 4

ER -