An enhanced CRISPR repressor for targeted mammalian gene regulation
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-...
Main Authors: | , , , , , , , , , , , , , , , , , , , |
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Other Authors: | , |
Format: | Article |
Language: | English |
Published: |
Nature Publishing Group,
2019-02-13T15:53:38Z.
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Subjects: | |
Online Access: | Get fulltext |
Summary: | 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. Paul G. Allen Frontiers Group |
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