Inhibition of CRISPR-Cas systems by mobile genetic elements

•Viruses and mobile genetic elements evolve countermeasures against CRISPR immunity.•'Anti-CRISPRs' are small proteins that inhibit the CRISPR-Cas machinery.•Type I and Type II CRISPR-Cas systems are inhibited by anti-CRISPRs.•Different anti-CRISPRs can act at distinct stages of target interference.

Clustered, regularly interspaced, short, palindromic repeats (CRISPR) loci, together with their CRISPR-associated (Cas) proteins, provide bacteria and archaea with adaptive immunity against invasion by bacteriophages, plasmids, and other mobile genetic elements. These host defenses impart selective pressure on phages and mobile elements to evolve countermeasures against CRISPR immunity. As a consequence of this pressure, phages and mobile elements have evolved 'anti-CRISPR' proteins that function as direct inhibitors of diverse CRISPR-Cas effector complexes. Some of these CRISPR-Cas complexes can be deployed as genome engineering platforms, and anti-CRISPRs could therefore be useful in exerting spatial, temporal, or conditional control over genome editing and related applications. Here we describe the discovery of anti-CRISPRs, the range of CRISPR-Cas systems that they inhibit, their mechanisms of action, and their potential utility in biotechnology.