Combating Antimicrobial Resistance by Resensitising Bacteria to Antibiotics Using CRISPR: A Narrative Review

Abstract

Background: Antimicrobial resistance (AMR) remains a formidable global health threat. Conventional strategy of developing new antibiotics is costly and unsustainable. Thus, innovative approaches for resensitising bacteria using clustered regularly inter-spaced short palindromic repeats (CRISPR) technology are sought. Aims and Objectives: The aim of this study was to review existing technologies and approaches with the aim to identify the most feasible and practical approach to solve AMR globally. Methods: It is a narrative review of CRISPR research to identify a practical medical solution for combating AMR. By considering biological, social and pharmaceutical factors, feasible solutions and their limitations were identified. Next, CRISPR solutions were examined, then filtered based on strict medical expectations. A suitable cargo type and delivery mechanism will be established. Finally, the feasibility from a practical and economic perspective is considered. Results: Among the Cas effector modules examined, Cas12k was identified as the most promising candidate. Notably, Cas12k possesses a small protein size and lacks trans-cleavage activity, enhancing its specificity for targeted bacterial strains. Additionally, its naturally inactivated endonuclease domain further contributes to its precision. In line with this investigation, DNA plasmid was identified as the optimal cargo storage, while lipid nanoparticles were identified as the optimal delivery method. Conclusion: This is the first time an end-to-end consideration to AMR was considered for CRISPR-based strategies. This review offers valuable insights into a promising solution to addressing the AMR crisis. Such knowledge is essential to guide the development of novel AMR solutions.