An enhanced CRISPR repressor for targeted mammalian gene regulation
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Collins_An enhanced CRISPR repressor manuscript figures supp materials.pdf
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Author(s) • • • • • • • • •
Yeo, Nan Cher
Chavez, Alejandro
Lance-Byrne, Alissa
Chan, Yingleong
Menn, David
Milanova, Denitsa
Kuo, Chih-Chung
Guo, Xiaoge
Sharma, Sumana
Tung, Angela
Date Issued
July 2018
Journal
Nature Methods
Publisher
Nature Publishing Group
Citation
Yeo, Nan Cher, et al. “An Enhanced CRISPR Repressor for Targeted Mammalian Gene Regulation.” Nature Methods, vol. 15, no. 8, Aug. 2018, pp. 611–16.
Version
Author's final manuscript
Abstract
The RNA-guided endonuclease Cas9 can be converted into a programmable transcriptional repressor, but inefficiencies in target-gene silencing have limited its utility. Here we describe an improved Cas9 repressor based on the C-terminal fusion of a rationally designed bipartite repressor domain, KRAB–MeCP2, to nuclease-dead Cas9. We demonstrate the system’s superiority in silencing coding and noncoding genes, simultaneously repressing a series of target genes, improving the results of single and dual guide RNA library screens, and enabling new architectures of synthetic genetic circuits.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/s41592-018-0048-5