An enhanced CRISPR repressor for targeted mammalian gene regulation.
Nat Methods
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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. |
Year of Publication | 2018
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Journal | Nat Methods
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Volume | 15
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Issue | 8
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Pages | 611-616
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Date Published | 2018 08
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ISSN | 1548-7105
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DOI | 10.1038/s41592-018-0048-5
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PubMed ID | 30013045
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PubMed Central ID | PMC6129399
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Grant list | P50 HG005550 / HG / NHGRI NIH HHS / United States
R35 GM119850 / GM / NIGMS NIH HHS / United States
RM1 HG008525 / HG / NHGRI NIH HHS / United States
T32 CA009216 / CA / NCI NIH HHS / United States
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