Nakamura, M. et al. Nat. Commun. 10, 194 (2019).

Li, B. et al. Cell Rep. 25, 3262–3272 (2018).

To make genome-editing applications more specific, it is desirable to fine-tune the temporal window during which CRISPR nucleases are active and to find ways to terminate their activity. Two research groups explored different ways to inhibit various functions of Cas proteins. Nakamura et al. characterized five anti-CRISPR (Acr) proteins for their inhibitory effects on Cas9 during gene activation and repression. They found AcrIIA4 to be the most potent inhibitor. Its expression protects a cell against CRISPR activity, which the authors say can be used as a prophylactic option if gene editing is to be limited in a population of organisms. Li et al. focused on Cas12a and found that a DNA oligonucleotide with phosphorothioate modifications potently inhibited the cleavage activity of Cas12a. They showed that the oligo forms a ternary complex with the guide RNA and Cas12a and prevents binding of the complex to the target DNA. Synthetic oligos and naturally occurring Acr proteins provide complementary ways to fine-tune CRISPR activities.