Abstract
Synthetic biology enables the rational engineering of microbes to create “living medicines.” This article focuses on two frontiers: (1) engineered bacteria that selectively target the tumour microenvironment to produce anti-cancer agents or immunomodulators locally; and (2) designed gut commensals that function as “sense-and-respond” systems, detecting inflammatory biomarkers and synthesising/releasing therapeutic molecules (e.g., anti-inflammatory peptides, metabolic enzymes) in situ to treat inflammatory bowel disease or metabolic disorders. We examine the translational progress and paramount biosafety considerations.
Proposed Structure
- Introduction: Limitations of conventional drug delivery; synthetic biology and the concept of living therapeutics.
- Engineered Bacteria for Oncology:
- Targeting hypoxic/immunosuppressive tumour niches.
- Local delivery of cytotoxins, checkpoint inhibitors, cytokines.
- Clinical pipeline examples (e.g., Synlogic, GenCirq).
- Engineered Microbes for Chronic Disease:
- For IBD: Sensing inflammatory signals (e.g., thiosulfate, tetrathionate), releasing anti-inflammatory molecules.
- For Inborn Errors of Metabolism: Constitutively supplementing missing enzymes in the gut (e.g., for PKU).
- Biosafety & Control Strategies: Auxotrophies, kill switches, biocontainment.
- Barriers to Translation: Manufacturing, regulatory path, long-term engraftment, and immunogenicity.
- Ethics & Outlook: Discussing long-term ecological impact and evolving regulatory frameworks.
Key References
- Gurbatri, C. R., & Danino, T. (2020). Engineering bacteria as interactive cancer therapies. Science, 368(6491), eaay3151.
- Kurtz, C. B., et al. (2019). An engineered E. coli Nissle 1917 improves hyperammonemia and survival in a mouse model of urea cycle disorder. Science Translational Medicine, 11(523), eaau7975.
- Isabella, V. M., et al. (2018). Development of a synthetic live bacterial therapeutic for the human metabolic disease phenylketonuria. Nature, 562(7726), 1-16.
