摘要: Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity RNA-programmable endonucleases, such as Cas9, or proteins comprising a Cas9 variant fused to functional effector domain, nuclease, nickase, recombinase, deaminase, transcriptional activator, repressor, epigenetic modifying domain. For example, inventive provided comprise ligand-dependent intein, presence which inhibits one more activities protein (e.g., gRNA binding, enzymatic activity, target DNA binding). The binding ligand intein results in self-excision restoring protein.