A Comprehensive Review on Phage Therapy and Phage-Based Drug Development

A Comprehensive Review on Phage Therapy and Phage-Based Drug Development

2024 | Longzhu Cui, Shinya Watanabe, Kazuhiko Miyanaga, Kotaro Kiga, Teppei Sasahara, Yoshifumi Aiba, Xin-E Tan, Srivani Veeranarayanan, Kanate Thitiananpakorn, Huong Minh Nguyen and Dammika Leshan Wannigama
Phage therapy, the use of bacteriophages to treat bacterial infections, is regaining momentum as a promising weapon against the rising threat of multidrug-resistant (MDR) bacteria. This review explores the historical context, the modern resurgence of phage therapy, and phage-facilitated advancements in medical and technological fields. It details the mechanisms of action and applications of phages in treating MDR bacterial infections, particularly those associated with biofilms and intracellular pathogens. The review further highlights innovative uses of phages in vaccine development, cancer therapy, and as gene delivery vectors. Despite its targeted and efficient approach, phage therapy faces challenges related to phage stability, immune response, and regulatory approval. By examining these areas in detail, this review underscores the immense potential and remaining hurdles in integrating phage-based therapies into modern medical practices. Phages have also demonstrated efficacy against biofilm-associated infections, which are notoriously difficult to treat with conventional antibiotics. Biofilms, which are structured communities of bacteria encased in a self-produced polymeric matrix, are implicated in chronic infections and are resistant to antibiotics and immune responses. Phages can penetrate biofilms, replicate within bacterial cells, and disrupt the biofilm matrix, making them potent agents against biofilm-associated infections. In addition to treating extracellular bacteria, phage therapy is being explored for its potential to target intracellular pathogens. Intracellular bacteria, such as Mycobacterium tuberculosis and Salmonella spp., reside within host cells, evading many antibiotics that cannot effectively penetrate cellular membranes. Advances in phage engineering and delivery mechanisms are opening new possibilities for using phages to combat these hidden infections. While phage therapy has demonstrated significant promise in addressing bacterial infections, it represents only one facet of phage-based drug development. Phage-based drug development encompasses a diverse range of innovative applications beyond traditional phage therapy for bacterial infections. Beyond their role in direct bacterial lysis, phages are being harnessed for various innovative applications, including vaccine development, cancer therapy, and as vectors for gene-delivery systems. Phage display technology, which involves expressing peptides or proteins on the surface of phage particles, has revolutionized vaccine development. This technology allows for the presentation of antigens in a highly immunogenic context, potentially leading to more effective vaccines. In oncology, phages are being investigated as anti-cancer agents. By engineering phages to target tumor-specific markers, researchers aim to selectively deliver therapeutic agents to cancer cells, thereby minimizing damage to healthy tissues. Additionally, the immunogenic properties of phages can stimulate an anti-tumor immune response, offering a dual mechanism of action against cancer. Phages also hold promise as drug-delivery systems (DDS) for gene therapy. Their ability to encapsulate and deliver genetic material to specific cells makes them ideal vectors for delivering therapeutic genes, including those used in CRISPR-Cas systems for gene editing. The specificity and efficiency of phage-mediated delivery systems could revolutionPhage therapy, the use of bacteriophages to treat bacterial infections, is regaining momentum as a promising weapon against the rising threat of multidrug-resistant (MDR) bacteria. This review explores the historical context, the modern resurgence of phage therapy, and phage-facilitated advancements in medical and technological fields. It details the mechanisms of action and applications of phages in treating MDR bacterial infections, particularly those associated with biofilms and intracellular pathogens. The review further highlights innovative uses of phages in vaccine development, cancer therapy, and as gene delivery vectors. Despite its targeted and efficient approach, phage therapy faces challenges related to phage stability, immune response, and regulatory approval. By examining these areas in detail, this review underscores the immense potential and remaining hurdles in integrating phage-based therapies into modern medical practices. Phages have also demonstrated efficacy against biofilm-associated infections, which are notoriously difficult to treat with conventional antibiotics. Biofilms, which are structured communities of bacteria encased in a self-produced polymeric matrix, are implicated in chronic infections and are resistant to antibiotics and immune responses. Phages can penetrate biofilms, replicate within bacterial cells, and disrupt the biofilm matrix, making them potent agents against biofilm-associated infections. In addition to treating extracellular bacteria, phage therapy is being explored for its potential to target intracellular pathogens. Intracellular bacteria, such as Mycobacterium tuberculosis and Salmonella spp., reside within host cells, evading many antibiotics that cannot effectively penetrate cellular membranes. Advances in phage engineering and delivery mechanisms are opening new possibilities for using phages to combat these hidden infections. While phage therapy has demonstrated significant promise in addressing bacterial infections, it represents only one facet of phage-based drug development. Phage-based drug development encompasses a diverse range of innovative applications beyond traditional phage therapy for bacterial infections. Beyond their role in direct bacterial lysis, phages are being harnessed for various innovative applications, including vaccine development, cancer therapy, and as vectors for gene-delivery systems. Phage display technology, which involves expressing peptides or proteins on the surface of phage particles, has revolutionized vaccine development. This technology allows for the presentation of antigens in a highly immunogenic context, potentially leading to more effective vaccines. In oncology, phages are being investigated as anti-cancer agents. By engineering phages to target tumor-specific markers, researchers aim to selectively deliver therapeutic agents to cancer cells, thereby minimizing damage to healthy tissues. Additionally, the immunogenic properties of phages can stimulate an anti-tumor immune response, offering a dual mechanism of action against cancer. Phages also hold promise as drug-delivery systems (DDS) for gene therapy. Their ability to encapsulate and deliver genetic material to specific cells makes them ideal vectors for delivering therapeutic genes, including those used in CRISPR-Cas systems for gene editing. The specificity and efficiency of phage-mediated delivery systems could revolution
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[slides and audio] A Comprehensive Review on Phage Therapy and Phage-Based Drug Development