Haonan Shao, Youpeng Deng, Yongpeng Shi, Z. H. Duan
The escalating crisis of antimicrobial resistance (AMR) and the stagnating antibiotic pipeline have renewed interest in bacteriophage therapy. While natural phages offer specificity and low toxicity, their narrow host range, bacterial resistance, and safety concerns limit clinical use. To overcome these hurdles, phages are being engineered using biotechnology. This review outlines the history of phage therapy and systematically summarizes advances in engineered phage preparation, including genetic modification, chemical conjugation, and physical encapsulation. We highlight the application of engineered phages against multidrug-resistant infections, gastrointestinal diseases through gut microbiome modulation, and as targeted delivery vehicles or immune adjuvants in cancer therapy. While significant advances have been made, several critical challenges remain, particularly in regulatory approval, large-scale manufacturing, and ensuring long-term safety. We conclude that engineered phages, as customizable and precise biological tools, are poised to advance precision phage medicine, offering a transformative solution to AMR and fostering convergence across synthetic biology, medicine, and environmental science.