Petris, G. et al. Nat. Commun. 8, 15334 (2017).

It is in the interest of specificity to limit the active time of the nuclease Cas9 when using CRISPR technology for genome editing. The shorter the duration of Cas9 activity, the less likely the enzyme is to cut at sites other than the intended target. Petris et al. developed SLiCES (self-limiting Cas9 circuit for enhanced safety and specificity), a genetic circuit in which a guide RNA targeting Cas9 to its intended site is coexpressed with a guide RNA that targets Cas9 itself and thus inactivates it. All components of SLiCES are delivered to cells via a lentiviral vector system and result in a several-fold increase in the specificity of several guide RNAs with known off-target activities. SLiCES can easily be adapted for other Cas species.