"Regulating Genome Engineering: The Role of Anti-CRISPR Proteins and Off-Switches"

Researchers have identified two anti-CRISPR proteins, AcrIC8 and AcrIC9, that can "turn off" the broad and unidirectional genome editing activity of the type I CRISPR protein Cas3, paving the way toward safer and better-controlled CRISPR applications. These proteins work by blocking the CRISPR-associated complex for anti-viral defense (Cascade) from engaging DNA targets, inhibiting Cas3-induced DNA deletion and gene activation. This discovery sets the stage for improved type I editing outcomes through temporal, spatial, tissue-specific, and light- or drug-controlled Acr regulation, offering tunable control beyond a simple on-off switch.