Narrative synthesis on CRISPR-Cas systems for multidrug-resistant bacterial infections

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Frontiers in Medicine Published May 11, 2026 Medically reviewed May 11, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider the preclinical promise of CRISPR-Cas for resistant infections but note major safety and delivery gaps.

This is a narrative synthesis of preclinical evidence on CRISPR-Cas systems for multidrug-resistant bacterial infections. The authors review the antibacterial activity of systems like Cas9, Cas12, and Cas13, finding they can induce chromosomal double-strand breaks, cure resistance plasmids, disrupt integrons, or cleave RNA to kill or resensitize bacteria. They note that phage-mediated delivery demonstrates the most consistent efficacy in complex environments and animal models, and that a CRISPR-enhanced engineered bacteriophage cocktail (LBP-EC01) has advanced to clinical evaluation.

The synthesis identifies key limitations, including a limited host range, instability in physiological environments, and the potential emergence of escape mutations. The authors also highlight insufficient data on off-target effects and long-term safety, which constrains conclusions about clinical applicability.

Practice relevance is not detailed in the source. The authors emphasize that current evidence is preclinical and observational, so causal claims about human outcomes are not supported. The synthesis calls for further research to address delivery challenges and safety concerns before broader clinical use.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

IntroductionThe rapid global increase in multidrug-resistant (MDR) bacteria has compromised the effectiveness of conventional antibiotics, stressing the urgent need for alternative antimicrobial strategies. CRISPR–Cas systems, originally evolved as bacterial adaptive immune mechanisms, provide programmable and highly specific tools for targeting antimicrobial resistance (AMR) determinants.ObjectiveThis systematic review aims to evaluate the antibacterial mechanisms, delivery strategies, preclinical evidence, safety considerations, and translational potential of CRISPR–Cas systems for combating MDR bacterial infections.MethodsA systematic literature search was conducted in PubMed, Scopus, Cochrane Library, and Web of Science up to January 2026 in accordance with PRISMA 2020 guidelines. Eligible studies included original in vitro and in vivo experimental or preclinical investigations assessing CRISPR–Cas systems (Cas9, Cas12, Cas13, or related effectors) for antibacterial activity or antibiotic resensitization. Data were extracted on CRISPR effector type, bacterial target, delivery platform, and therapeutic outcome. Due to methodological heterogeneity, results were synthesized narratively.ResultsMost studies reported effective killing or resensitization of MDR bacteria through chromosomal double-strand break induction, resistance plasmid curing, integron disruption, or RNA-targeted cleavage. Cas9 was the most frequently employed effector, followed by Cas12 and Cas13. Delivery strategies included bacteriophages, conjugative plasmids, and nanoparticle-based systems, with phage-mediated delivery demonstrating the most consistent efficacy in complex environments and animal models. Notably, a CRISPR-enhanced engineered bacteriophage cocktail (LBP-EC01) has advanced to clinical evaluation.DiscussionOverall, the evidence supports CRISPR–Cas antimicrobials as a promising precision-based approach for addressing AMR. However, major barriers remain, including limited host range, instability in physiological environments, emergence of escape mutations, and insufficient data on off-target effects and long-term safety. Addressing these challenges through optimized delivery platforms, multiplex targeting strategies, and standardized safety and regulatory frameworks will be essential for clinical translation.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261319789, identifier CRD4201319789.