South Asian Journal of Research in Microbiology

Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins comprise adaptive immune systems that enable bacteria and archaea to record encounters with mobile genetic elements and to eliminate subsequent invasions through RNA-guided nucleic acid targeting. Insights into spacer acquisition, guide RNA biogenesis, and interference have been translated into a versatile toolkit for genome and transcriptome engineering. This review integrates mechanistic principles of CRISPR–Cas function with the major classes of engineered editors, spanning double-strand break–mediated gene disruption and repair-dependent modification, and newer precision approaches designed to reduce reliance on error-prone repair. Particular attention is given to how effector diversity expands editing capabilities, including DNA-targeting nucleases and RNA-targeting systems that support transient and reversible interventions. The therapeutic potential of CRISPR technologies is evaluated across ex vivo and in vivo strategies, with emphasis on delivery constraints, immunogenicity, genomic safety, and the need for controllable activity windows. Key translational challenges include the heterogeneity of on-target repair outcomes, the possibility of off-target activity, and manufacturing and monitoring requirements for durable clinical benefit. The review also examines how natural inhibitory mechanisms can inform engineered safety controls, and it situates biomedical innovation within broader ethical, legal, and social debates. These debates encompass proportionality of risk in somatic editing, governance of heritable interventions, equity in access to advanced therapies, environmental implications of population-scale genetic tools, and dual-use concerns. Collectively, the evidence indicates that CRISPR–Cas systems can reshape biomedical practice, provided that technical advances are matched by rigorous safety assessment and responsible governance.