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Nat Methods. 2017 Dec;14(12):1163-1166. doi: 10.1038/nmeth.4483. Epub 2017 Oct 30.

Inducible and multiplex gene regulation using CRISPR-Cpf1-based transcription factors.

Author information

1
Molecular Pathology Unit, Center for Cancer Research, and Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
2
Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
3
Department of Cellular & Molecular Pharmacology University of California, San Francisco, San Francisco, California, USA.
4
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
5
Howard Hughes Medical Institute, San Francisco, California, USA.

Abstract

Targeted and inducible regulation of mammalian gene expression is a broadly important capability. We engineered drug-inducible catalytically inactive Cpf1 nuclease fused to transcriptional activation domains to tune the expression of endogenous genes in human cells. Leveraging the multiplex capability of the Cpf1 platform, we demonstrate both synergistic and combinatorial gene expression in human cells. Our work should enable the development of multiplex gene perturbation library screens for understanding complex cellular phenotypes.

PMID:
29083402
PMCID:
PMC5909187
DOI:
10.1038/nmeth.4483
[Indexed for MEDLINE]
Free PMC Article

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