Synthetic biology of oncolytic bacteria: Comparative microbial chassis and precise killing strategies

The field of synthetic biology has become a revolutionary tool for engineering microorganisms capable of precise, programmed cancer treatment. Unlike conventional cancer treatments, which lack safe, selective toxicity, engineered microbial cells can detect tumor-specific signals, target hypoxic environments, and deliver cytotoxic payloads more effectively in both space and time. This review presents the most recent advancements in microbial chassis engineering, including Escherichia coli, Salmonella, Clostridium, Bifidobacterium, Vibrio cholera, Shigella species and L. monocytogenes along with their potential uses in targeted cancer therapy through toxin delivery, prodrug conversion, immune modulation, and tumor-specific surface display. We discuss key synthetic biology techniques that enhance safety, specificity, and genetic stability, including clustered regularly interspaced short palindromic repeat-associated protein 9 (CRISPR/Cas9)-based genome editing, genetic logic circuits, and kill-switch systems. This review provides some highlights about the role of synthetic biology in developing oncolytic bacteria with precise targeting abilities and enhanced therapeutic stability. By analyzing comparative microbial chassis and the implementation of precise killing strategies, we address current clinical challenges and explore the future of oncolytic bacterial therapy.