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Nat Rev Mol Cell Biol. 2016 Jan;17(1):5-15. doi: 10.1038/nrm.2015.2. Epub 2015 Dec 16.

Beyond editing: repurposing CRISPR-Cas9 for precision genome regulation and interrogation.

Dominguez AA1,2,3, Lim WA4,5,6,7, Qi LS1,2,3.

Author information

1
Department of Bioengineering, Stanford University, Stanford, California 94305, USA.
2
Department of Chemical and Systems Biology. Stanford University, Stanford, California 94305, USA.
3
Stanford ChEM-H, Stanford University, Stanford, California 94305, USA.
4
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA.
5
Howard Hughes Medical Institute, University of California, San Francisco, California 94158, USA.
6
UCSF Center for Systems and Synthetic Biology, University of California, San Francisco, California 94158, USA.
7
California Institute for Quantitative Biomedical Research (QB3), University of California, San Francisco, California 94158, USA.

Abstract

The bacterial CRISPR-Cas9 system has emerged as a multifunctional platform for sequence-specific regulation of gene expression. This Review describes the development of technologies based on nuclease-deactivated Cas9, termed dCas9, for RNA-guided genomic transcription regulation, both by repression through CRISPR interference (CRISPRi) and by activation through CRISPR activation (CRISPRa). We highlight different uses in diverse organisms, including bacterial and eukaryotic cells, and summarize current applications of harnessing CRISPR-dCas9 for multiplexed, inducible gene regulation, genome-wide screens and cell fate engineering. We also provide a perspective on future developments of the technology and its applications in biomedical research and clinical studies.

PMID:
26670017
PMCID:
PMC4922510
DOI:
10.1038/nrm.2015.2
[Indexed for MEDLINE]
Free PMC Article

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