CRISPR-based gene editing for antimicrobial resistance control in human medicine.

Antimicrobial resistance (AMR) has already become one of the most urgent threats to the public health of this century. In 2019 alone, it directly causes about 1.27 million deaths and it was estimated that 1.91 million people will die yearly by 2050 should present trends persist. The traditional antibiotic development pipelines have been shown to be structurally insufficient to meet the rate at which bacterial populations have developed, diversified and spread resistance determinants, typically by horizontal gene transfer. In this context, CRISPR-Cas gene editing has become a focused antimicrobial approach that can selectively target resistance genes, virulence factors, and mobile genetic elements without the broad-spectrum collateral damage associated with conventional antibiotics. The review assesses CRISPR-Cas systems, namely Cas9, Cas12a, Cas3, and Cas13 in the context of two complementary mechanistic strategies namely selective killing of pathogens and antibiotic resensitization by the targeted disruption of gene resistance. We compare the impact of key delivery systems, such as bacteriophage vectors, lipid nanoparticles, and conjugative plasmids, evaluating them based on their therapeutic activity, host selectivity, and possible translation. The present state of clinical translations is discussed, including the two most advanced clinical-stage candidates SNIPR001 (Phase I/II, NCT05277350) and LBP-EC01 (Phase 2/3, NCT05488444). We also address the open issues that include off-target editing, host immune reactions, bacterial counter-resistance, regulatory ambiguity, and scalability of manufacturing. Lastly, we provide priority research directions, such as the combination antimicrobial strategies, AI-assisted CRISPR design, and next-generation delivery engineering, none of which will be resolved before routine clinical application of CRISPR-based antimicrobials is achieved.