Davis, KevinPattanayak, VikramThompson, DavidZuris, John A.Liu, David2015-12-042015Davis, Kevin M., Vikram Pattanayak, David B. Thompson, John A. Zuris, and David R. Liu. 2015. “Small Molecule-Triggered Cas9 Protein with Improved Genome-Editing Specificity.” Nature chemical biology 11 (5): 316-318. doi:10.1038/nchembio.1793. http://dx.doi.org/10.1038/nchembio.1793.1552-4450http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845300Directly 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 (4-HT)-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.en-USJournal Article2015-12-0410.1038/nchembio.1793