Antimicrobial resistance (AMR) has become a major global health challenge, threatening the effectiveness of antibiotics that have long been the foundation of modern medicine. The increasing prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria has resulted in rising morbidity, mortality, and healthcare costs worldwide, highlighting the urgent need for innovative antimicrobial strategies. Conventional antibiotics often exert broad-spectrum effects, disrupting beneficial microbial communities and accelerating the emergence of resistance. In response, CRISPR-Cas systems have emerged as promising precision antimicrobial tools capable of selectively targeting bacterial genomes, resistance genes, virulence determinants, and mobile genetic elements with high specificity.

This review explores the molecular basis of AMR, including enzymatic drug inactivation, target modification, efflux-mediated resistance, biofilm formation, and horizontal gene transfer. It further examines the diversity of CRISPR-Cas systems and their application in bacterial killing, plasmid curing, gene silencing, and microbiome modulation. Particular attention is given to the delivery challenges associated with CRISPR therapeutics and the role of nanotechnology in overcoming these barriers. Nanocarrier platforms, including lipid nanoparticles, polymeric nanoparticles, biomimetic systems, and phage-derived carriers, provide enhanced protection, targeted delivery, improved biofilm penetration, and controlled release of CRISPR cargo. The review also highlights the growing contribution of computational approaches, such as molecular docking, molecular dynamics simulations, and artificial intelligence-assisted design, in optimizing guide RNAs and nanocarrier performance. Current experimental evidence demonstrates that Nano-CRISPR systems can effectively combat resistant pathogens, disrupt biofilms, and restore antibiotic susceptibility. Collectively, these advances position Nano-CRISPR therapeutics as a promising next-generation strategy for precision antimicrobial intervention in the fight against AMR.

Keywords: AMR, CRISPR, Nanocarrier, Precision Antimicrobials, MDR bacteria