Research on Anti-CRISPR Applications in Gene Editing, Biotechnology and Medicine

CRISPR-Cas systems serve as adaptive immune mechanisms in prokaryotes, while mobile genetic elements like phages have evolved anti-CRISPR proteins (Acrs) to evade this defense. This review synthesizes the principles, mechanisms, and diverse applications of Acrs, highlighting their roles in precision gene editing, gene drive regulation, phage therapy, and optogenetics. Acrs inhibit CRISPR-Cas through multiple mechanisms, including direct binding to Cas nuclease active sites, spatial occlusion of nucleic acid binding sites, induction of conformational changes in Cas complexes, and enzymatic degradation of CRISPR components, which enable precise control of CRISPR activity. In gene drive systems, Acrs act as safety switches to mitigate unintended genetic spread in organisms like Saccharomyces cerevisiae. For phage therapy, engineered phages effectively combat CRISPR-resistant Pseudomonas aeruginosa infections, while Acrs may also inadvertently facilitate antibiotic resistance plasmid spread in pathogens like Klebsiella pneumoniae. This review underscores Acrs as versatile regulators of CRISPR technology, balancing precision and safety across biomedical and ecological applications, while emphasizing the need for deeper mechanistic insights and translational research.