Recent advances of engineered bacteria for therapeutic applications

Mol Ther. 2026 Feb 4;34(2):714-733. doi: 10.1016/j.ymthe.2025.11.013. Epub 2025 Nov 12.

Abstract

Engineered bacterial systems have been widely utilized as versatile biotherapeutic platforms in disease intervention, yet their therapeutic efficacy remains limited. Recent advancements in synthetic biology have enabled the systematic deconstruction of bacteria through rational computational modeling and modular-genetic circuit design, thereby overcoming intrinsic functional limitations. These engineered bacteria represent a promising therapeutic strategy characterized by enhanced spatiotemporal precision, biosafety profiles, and scalable production. Moreover, the advent of sophisticated genetic engineering technologies has facilitated the expansion of bacterial therapeutic applications into new areas, including vaccine development and tumor-microenvironment modulation. Here, we systematically examine recent advances in the development and testing of engineered bacteria across different organs on the basis of tissue specificity. We further summarize the therapeutic roles of engineered bacteria in tumor treatment and metabolic-disorder management. Additionally, we outline advanced technologies for engineered bacterial development, emphasizing their critical roles in optimizing the overall clinical efficacy of therapeutic agents after system-level optimization.

Keywords: bacterial therapeutics; engineered bacteria; genetic circuit; metabolic disorders; synthetic biology.

Publication types

  • Review

MeSH terms

  • Animals
  • Bacteria* / genetics
  • Bacteria* / metabolism
  • Genetic Engineering* / methods
  • Humans
  • Neoplasms / therapy
  • Synthetic Biology / methods
  • Tumor Microenvironment