Small molecule–triggered Cas9 protein with improved genome-editing specificity
April 6th, 2015 by Kevin M Davis
Nature Chemical Biology 11, 316 (2015). doi:10.1038/nchembio.1793
Authors: Kevin M Davis, Vikram Pattanayak, David B Thompson, John A Zuris & David R Liu
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.