AntiCRISPR

Anti-CRISPR refers to a class of small proteins encoded by bacteriophages, plasmids, and other mobile genetic elements that inhibit CRISPR-Cas immune systems in bacteria and archaea. These proteins enable invading elements to overcome host defenses by disabling one or more components of the CRISPR–Cas machinery, thereby facilitating infection and horizontal gene transfer. Anti-CRISPRs were first described in studies of Pseudomonas phages around 2013 and have since been found in diverse bacterial lineages.

Most anti-CRISPR proteins target type I and type II CRISPR-Cas systems, with several families characterized by distinct mechanisms. Some bind to Cas nucleases or to the Cascade complex to prevent DNA binding or cleavage; others mimic DNA or RNA to block the active site; others promote degradation or destabilization of Cas proteins or prevent the assembly of CRISPR complexes. Representative examples include AcrF1–AcrF3, which inhibit type I-F systems in Pseudomonas, and AcrIIA4, which potently inhibits Streptococcus pyogenes Cas9; additional Acrs have been described for other Cas variants such as II-C and III systems.

Applications of anti-CRISPRs in biotechnology include temporal and contextual control of CRISPR-Cas–mediated genome editing, improved specificity by gating editing with Acr availability, and the study of CRISPR-Cas dynamics. They also have potential in phage therapy and in biosafety strategies to prevent unintended CRISPR activity in engineered organisms. Limitations include uneven distribution among CRISPR types, context-dependent activity, and concerns about horizontal transfer of anti-CRISPR genes.