Phage-based CRISPR delivery systems for targeted eradication of drug-resistant bacterial infections
1 Department of Treatment Care and Support, AIDS Healthcare Foundation Lokoja, Nigeria.
2 Department of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University Poland.
3 Department of Biomedical Ethics, CIS, Hamad Bin Khalifa University, Doha, Qatar.
4 Department of Microbiology, Chukwuemeka Odumegwu Ojukwu University, Uli, Nigeria.
5 Department of Biochemistry, Federal University of Technology Akure, Ondo, Nigeria.
6 Department of Medical Laboratory Sciences, University of Nigeria Nsukka.
7 Department of Microbiology, Umaru Musa Yar'adua University, Katsina, Nigeria.
Review
International Journal of Life Science Research Archive, 2025, 09(01), 006-034.
Article DOI: 10.53771/ijlsra.2025.9.1.0042
Publication history:
Received on 29 May 2025; revised on 05 July 2025; accepted on 07 July 2025
Abstract:
The alarming rise of antimicrobial resistance (AMR) has propelled the global scientific community to seek novel, precise, and effective antibacterial strategies beyond conventional antibiotics. Among these, CRISPR-Cas systems have emerged as powerful genome-editing tools capable of selectively targeting and disabling resistance genes. However, the therapeutic utility of CRISPR hinges critically on the development of efficient, safe, and host-specific delivery vectors. Bacteriophages viruses that naturally infect bacteria offer a promising platform for precision delivery due to their inherent specificity and genetic malleability. This review explores the rapidly evolving landscape of phage-based CRISPR delivery systems as next-generation antimicrobials against drug-resistant pathogens. It delves into the engineering of lytic and lysogenic phages to carry CRISPR constructs targeting β-lactamase genes, plasmid-borne resistance elements, and essential virulence determinants. We critically examine the mechanisms of CRISPR-mediated bacterial killing via DNA cleavage and programmable bactericidal action, and evaluate preclinical models demonstrating successful eradication of multidrug-resistant strains such as Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. Furthermore, the review highlights emerging innovations including phage tail fiber reprogramming for broadened host range, and combinatorial phage-CRISPR cocktails to suppress resistance evolution. Ethical and regulatory considerations, as well as challenges in large-scale biomanufacturing, are also addressed. By converging the molecular precision of CRISPR with the delivery versatility of bacteriophages, this hybrid strategy represents a transformative paradigm for combating the global AMR crisis and ushering in an era of programmable antibacterial therapeutics.
Keywords:
Phage Therapy; Crispr-Cas; Antimicrobial Resistance; Bacteriophage Delivery; Gene Editing; Synthetic Biology; Precision Medicine; Microbial Targeting
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Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0