Jul 2026· International journal of pharmaceutics· pp.
127155
· 0 citations· 127 references
Medicine
Abstract
The rapid emergence of multidrug-resistant (MDR) bacteria has increased interest in bacteriophage therapy as a promising alternative to conventional antibiotics. Bacteriophages are host-specific bacterial viruses that selectively infect and destroy pathogenic bacterial strains. Recent developments in artificial intelligence (AI) and CRISPR-based technologies offer innovative approaches to address challenges such as narrow host range, rapid immune clearance, phage instability, bacterial resistance, and biofilm penetration barriers. By integrating AI-driven structural modeling with CRISPR-mediated genome editing, these methods enable the targeted delivery of bacteriophages. This review focuses on next-generation approaches that combine AI-assisted phage identification, host prediction, and therapeutic optimization with CRISPR-based genome engineering for targeted phage delivery and improved safety. Overall, this review highlights the potential of AI- and CRISPR-assisted phage therapy for the treatment of MDR bacterial infections. This review provides a systematic overview of bacteriophage biology, life cycle, and mechanisms of action, highlighting the influence of phage morphology on therapeutic performance, recent advances, current clinical and preclinical studies, and future perspectives. Although phage therapy shows considerable potential against MDR bacterial infections, several challenges related to delivery, safety, and clinical translation remain. The integration of AI and CRISPR technologies may improve phage selection, targeting specificity, and therapeutic performance. Continued research, clinical validation, and regulatory development will be essential for translating these advances into practical antimicrobial therapies.
This review critically examines bacteriophage-based antimicrobials, CRISPR-Cas therapeutic systems, and their emerging integration as CRISPR-armed phages, highlighting their comparative advantages, current limitations, and future potential as promising targeted antimicrobial approach platforms requiring further clinical validation.
Anjaneyulu Musini, V. Yata, S. Bukke et al.· Molecular Biology Reports· 0 citations
The increasing clinical evidence shows that synthetic biology can effectively overcome the inherent defects of natural bacteriophages, confirming the safety and initial efficacy of bacteriophage therapy.
Xuan Wang, Haolin Zhou, T. S. Lim et al.· International Journal of Mol...· 0 citations
Accumulating experimental and clinical evidence indicates that bacteriophage therapy could become an important component of future antimicrobial strategies, and Continued multidisciplinary research, standardized clinical protocols, and well-designed randomized clinical trials are essential to establish its long-term efficacy and safety.
Himadri Sharma· International Journal of Res...· 0 citations
This study investigates the CRISPR-Cas framework’s potential as a cutting-edge tactic to fight antimicrobial resistance, and finds that the efficiency of CRISPR-Cas is diminished in some bacterial strains due to variations in their CRISPR loci.
Akmal Zubair, M. Hemal, Alaeldeen Ahmed et al.· Archives of Microbiology· 0 citations
Overall, CRISPR-based antimicrobial therapy represents a transformative approach to precision infectious disease management, with continued technological innovation, interdisciplinary collaboration, and robust clinical validation expected to facilitate its safe, effective, and clinically accessible implementation against multidrug-resistant pathogens.
Dipankar Mukhopadhyay, Dr. Shilanjali Bhalerao, Dr. Vijayendra Gautam et al.· Genetics and Molecular Resea...· 0 citations
Phage therapy has been revisited as a biologically based strategy to tackle the escalating global crisis of multidrug-resistant (MDR) bacterial infections. Distinct from conventional antibiotics, bacteriophages target specific bacterial strains precisely, replicate locally at infection sites, penetrate bacterial biofilms, and exert synergistic effects with multiple antimicrobial agents. These inherent mechanistic advantages minimize collateral damage to the host’s commensal microbiota. However, existing regulatory frameworks—originally established for chemically synthesized, mass-produced drugs—fail to accommodate personalized, living biological phage products, leading to uncertain approval pathways and inconsistent manufacturing supervision. Clinical experience of phage therapy is predominantly derived from compassionate-use cases via multiple administration routes, including intravenous, inhaled, and topical delivery. This review systematically analyzes major challenges restricting clinical application, such as standardized production, quality control, pharmacokinetic characterization, rapid pathogen identification, and regulatory adaptation, as well as the limited performance of fixed phage cocktails against genetically heterogeneous bacterial populations. Current clinical practice demonstrates that phage therapy exhibits acceptable safety profiles across intravenous, inhaled, and topical administration routes, with promising therapeutic outcomes in otherwise untreatable MDR infections. Nevertheless, stable and reproducible clinical outcomes are hindered by multiple scientific and operational obstacles: the absence of unified standards for phage production and quality control, insufficient understanding of route-dependent pharmacokinetics, the imperative demand for rapid pathogen identification to enable precise phage matching, and the limited efficacy of fixed-cocktail regimens against genetically diverse clinical isolates. The successful integration of phage therapy into routine clinical practice relies on coordinated progress in diagnostic infrastructure construction, GMP-compliant phage repository establishment, international regulatory harmonization, and high-quality evidence generation through well-designed clinical trials. Rather than serving as a universal substitute for antibiotics, phage therapy is best implemented as a precision complementary component within comprehensive antimicrobial stewardship strategies.
