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Nat Chem Biol. 2015 May;11(5):316-8. doi: 10.1038/nchembio.1793. Epub 2015 Apr 6.

Small molecule-triggered Cas9 protein with improved genome-editing specificity.

Author information

1
1] Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA.
2
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Abstract

Directly modulating the activity of genome-editing proteins has the potential to increase their specificity by reducing activity following target locus modification. We developed Cas9 nucleases that are activated by the presence of a cell-permeable small molecule by inserting an evolved 4-hydroxytamoxifen-responsive intein at specific positions in Cas9. In human cells, conditionally active Cas9s modify target genomic sites with up to 25-fold higher specificity than wild-type Cas9.

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PMID:
25848930
PMCID:
PMC4402137
DOI:
10.1038/nchembio.1793
[Indexed for MEDLINE]
Free PMC Article

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