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

Nat Chem Biol
Authors
Keywords
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.

Year of Publication
2015
Journal
Nat Chem Biol
Volume
11
Issue
5
Pages
316-8
Date Published
2015 May
ISSN
1552-4469
DOI
10.1038/nchembio.1793
PubMed ID
25848930
PubMed Central ID
PMC4402137
Links
Grant list
F32 GM 106601-2 / GM / NIGMS NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
Howard Hughes Medical Institute / United States
F32 GM106601 / GM / NIGMS NIH HHS / United States
R01 GM095501 / GM / NIGMS NIH HHS / United States