{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Life Sciences",
    "Nanjing University",
    "Nanjing Foreign Language",
    "School of Chemistry",
    "Wuxi Xishan NJU Institute of Applied Biotechnology",
    "Sino-Danish Ecolife Science Industrial Incubator, Jiangbei New Area, Nanjing, China, 210000"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Lihao Ji"
    },
    {
      "affs": [
        2
      ],
      "name": "Haomiao Huang"
    },
    {
      "affs": [
        3,
        1
      ],
      "name": "Yuhan Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tianqi Jiang"
    },
    {
      "affs": [
        4
      ],
      "name": "Zipeng Chen"
    },
    {
      "affs": [
        0,
        1,
        3,
        4,
        5
      ],
      "name": "Xiuxiu Wang"
    },
    {
      "affs": [
        0,
        1,
        3,
        4,
        5
      ],
      "name": "Jing Zhao"
    },
    {
      "affs": [
        0,
        1,
        3,
        4,
        5
      ],
      "name": "Wei Wei"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3mcgrzbyf06f0.bib",
  "cited_by": 0,
  "doi": "10.26434/chemrxiv.15010085/v1",
  "fulltext_url": null,
  "id": "3mcgrzbyf06f0",
  "issns": [],
  "landing_url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010085/v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1305|Cancer Research and Treatments"
    ]
  ],
  "openalex": "W7220923254",
  "pdf_url": "https://chemrxiv.org/doi/pdf/10.26434/chemrxiv.15010085/v1",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-08",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/3mcgrzbyf06f0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:22Z",
      "native_id": "10.26434/chemrxiv.15010085",
      "source": "chemrxiv",
      "url": "https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010085/v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1305|Cancer Research and Treatments",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Engineering Bacteria and Their Vesicles for Therapy: Integrating Native Functions, Genetic Control, and Chemical Biology",
  "title_text": "Engineering Bacteria and Their Vesicles for Therapy: Integrating Native Functions, Genetic Control, and Chemical Biology",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:22Z",
  "url": "https://research.draconitic.com/paper/3mcgrzbyf06f0",
  "venue": "ChemRxiv",
  "versions": []
}