Discovery of selective inhibitors of nuclear export as CRISPR-Cas9 off switch

CRISPR-Cas9 are associated with unwanted mutation that are deemed to result from constitutively active Cas9 nuclease. To overcome the off-target events, temporal control of CRISPR-Cas9 activity using selective off-switches has been investigated. In the present study, we sought to develop small molecule inhibitors to CRISPR-Cas9 and surprisingly discovered that selective inhibitors of nuclear export could indirectiy inhibit CRISPR-Cas9 activity by interfering with the nuclear export process of Cas9 mRNA.