Engineering Bacteria and Their Vesicles for Therapy: Integrating Native Functions, Genetic Control, and Chemical Biology
6 affiliations
- 1State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences
- 2Nanjing University
- 3Nanjing Foreign Language
- 4School of Chemistry
- 5Wuxi Xishan NJU Institute of Applied Biotechnology
- 6Sino-Danish Ecolife Science Industrial Incubator, Jiangbei New Area, Nanjing, China, 210000
Abstract
Bacteria possess native capabilities that are difficult to reproduce using conventional therapeutic platforms, including active motility, environmental adaptation, localized proliferation, metabolite production, immune stimulation, and interactions with host-associated microbial communities. However, bacterial therapeutics are frequently organized either by microbial species or by engineering technology, obscuring how chassis selection, functional modification, and clinical application should be coordinated. This review presents a chassis-first framework for the development of bacterial therapeutics. We define the functional requirements associated with cancer, intestinal inflammation, metabolic disorders, infectious diseases, and vaccination, and classify therapeutic bacteria into established chassis, microbiome-derived chassis, and function-driven unconventional chassis. We then examine two complementary engineering routes. Genetic engineering enables attenuation, disease-responsive sensing, therapeutic-payload production, controlled release, and biological containment, whereas chemical biology–enabled biohybrid engineering introduces targeting, protection, catalytic activity, and external control through surface functionalization, bacteria-mediated biosynthesis and biomineralization, and whole-cell coating. Because living bacteria retain risks associated with replication, dissemination, and evolutionary instability, we further discuss therapeutic termination strategies and compare whole-cell systems with nonreplicating outer membrane vesicles and related membrane-based platforms. Finally, we examine the clinical translation of bacterial medicines in terms of administration route, biodistribution, pharmacodynamics, manufacturing, safety, and regulatory control. Collectively, this review proposes that bacterial therapeutics should be designed within an integrated framework linking native chassis phenotype, engineering module, and clinical scenario, thereby shifting the field from opportunistic strain modification toward function-guided and translationally tractable therapeutic design.
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BibTeX
@misc{ji2026engineering,
title = {{Engineering Bacteria and Their Vesicles for Therapy: Integrating Native Functions, Genetic Control, and Chemical Biology}},
author = {Lihao Ji and Haomiao Huang and Yuhan Zhang and Tianqi Jiang and Zipeng Chen and Xiuxiu Wang and Jing Zhao and Wei Wei},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010085/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010085/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Engineering Bacteria and Their Vesicles for Therapy: Integrating Native Functions, Genetic Control, and Chemical Biology
AU - Lihao Ji
AU - Haomiao Huang
AU - Yuhan Zhang
AU - Tianqi Jiang
AU - Zipeng Chen
AU - Xiuxiu Wang
AU - Jing Zhao
AU - Wei Wei
PY - 2026
DA - 2026/10/08
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010085/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010085/v1
AB - Bacteria possess native capabilities that are difficult to reproduce using conventional therapeutic platforms, including active motility, environmental adaptation, localized proliferation, metabolite production, immune stimulation, and interactions with host-associated microbial communities. However, bacterial therapeutics are frequently organized either by microbial species or by engineering technology, obscuring how chassis selection, functional modification, and clinical application should be coordinated. This review presents a chassis-first framework for the development of bacterial therapeutics. We define the functional requirements associated with cancer, intestinal inflammation, metabolic disorders, infectious diseases, and vaccination, and classify therapeutic bacteria into established chassis, microbiome-derived chassis, and function-driven unconventional chassis. We then examine two complementary engineering routes. Genetic engineering enables attenuation, disease-responsive sensing, therapeutic-payload production, controlled release, and biological containment, whereas chemical biology–enabled biohybrid engineering introduces targeting, protection, catalytic activity, and external control through surface functionalization, bacteria-mediated biosynthesis and biomineralization, and whole-cell coating. Because living bacteria retain risks associated with replication, dissemination, and evolutionary instability, we further discuss therapeutic termination strategies and compare whole-cell systems with nonreplicating outer membrane vesicles and related membrane-based platforms. Finally, we examine the clinical translation of bacterial medicines in terms of administration route, biodistribution, pharmacodynamics, manufacturing, safety, and regulatory control. Collectively, this review proposes that bacterial therapeutics should be designed within an integrated framework linking native chassis phenotype, engineering module, and clinical scenario, thereby shifting the field from opportunistic strain modification toward function-guided and translationally tractable therapeutic design.
ER -