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Applied Sciences OPEN ACCESS

Engineered Bacteria as Living Therapeutics: Design, Applications, and Clinical Challenge

Ishika Baranwal
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Gomti Nagar Extension, Lucknow - 226028, India
Aditi Singh
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Lucknow Campus, Gomti Nagar Extension, Lucknow - 226028, India
DOI Crossref DOI 10.37547/tajas/warm-06
tajas 2026
JOURNAL PUBLICATION MAY
VOLUME —
ISSUE —
YEAR 2026
PAGES 56-63

Abstract

Living therapeutics" is an innovative category of living organisms that can be engineered to prevent, detect, and treat human diseases. With the help of synthetic biology and genetic engineering, microbial cells with the ability to recognize disease-associated cues, synthesize drugs within the host body, and respond to complex biological environments have now been created. This review explores the fundamental approaches used for constructing engineered bacteria, such as the creation of synthetic gene circuits, selecting suitable hosts or chassis, and incorporating biosensing and biocontainment strategies. Finally, we discuss the primary applications of engineered bacteria with a focus on gastrointestinal disease treatment, cancer therapy, metabolic disease management, and infectious disease treatment. Despite all of this, however, there are numerous hurdles yet to be conquered, including issues related to safety, genetic stability, targeted delivery, and regulatory clearance. For bacterial systems to move from the lab bench to the bedside, certain parameters need to be taken care of. On the whole, genetically modified bacteria represent an exciting frontier within the field of precision medicine, with the capacity to revolutionize therapeutic strategies with highly selective interventions.

Keywords

Genetic engineering CRISPR-Cas Escherichia coli Lactobacillus

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References

  1. Brewer AM, George DR, Frow EK. Emerging governance considerations for the deployment of genetically engineered microbes. Curr Opin Microbiol. 2026;89:102685. https://doi.org/10.1016/j.mib.2025.102685
  2. Charbonneau, M. R., Isabella, V. M., Li, N., & Kurtz, C. B. (2020). Developing a new class of engineered live bacterial therapeutics to treat human diseases. Nature Communications, 11, 1738. https://doi.org/10.1038/s41467-020-15508-1
  3. Chowdhury, S., Castro, S., Coker, C., Hinchliffe, T. E., Arpaia, N., & Danino, T. (2019). Programmable bacteria induce durable tumor regression and systemic antitumor immunity. Nature Medicine, 25(7), 1057–1063. https://doi.org/10.1038/s41591-019-0498-z
  4. Cryan, J. F., O’Riordan, K. J., Cowan, C. S. M., et al. (2019). The microbiota–gut–brain axis. Physiological Reviews, 99(4), 1877–2013. https://doi.org/10.1152/physrev.00018.2018
  5. Cubillos-Ruiz, A., Guo, T., Sokolovska, A., Miller, P. F., Collins, J. J., & Lu, T. K. (2021). Engineering living therapeutics with synthetic biology. Nature Reviews Drug Discovery, 20(12), 941–960. https://doi.org/10.1038/s41573-021-00286-9
  6. Din, M. O., Danino, T., Prindle, A., Skalak, M., Selimkhanov, J., Allen, K., & Hasty, J. (2016). Synchronized cycles of bacterial lysis for in vivo delivery. Nature, 536(7614), 81–85. https://doi.org/10.1038/nature18930
  7. Gulig, P., Swindle, S., Fields, M., & Eisenman, D. (2024). A Review of Clinical Trials Involving Genetically Modified Bacteria, Bacteriophages and Their Associated Risk Assessments. Applied biosafety : journal of the American Biological Safety Association, 29(4), 186–206. https://doi.org/10.1089/apb.2024.0002
  8. Isabella, V. M., Ha, B. N., Castillo, M. J., Lubkowicz, D. J., Rowe, S. E., Millet, Y. A., & Kurtz, C. B. (2018). Development of a synthetic live bacterial therapeutic for phenylketonuria. Nature Biotechnology, 36(9), 857–864. https://doi.org/10.1038/nbt.4222
  9. Landry, B. P., Tabor, J. J., & Weber, W. (2021). Engineering diagnostic and therapeutic gut bacteria. Microbiology Spectrum, 9(1), e00030-21. https://doi.org/10.1128/Spectrum.00030-21
  10. Lerner, A., Lieber, A. D., Nelson-Dooley, C., Leu, A., Perro, M., Koch, G., Benzvi, C., & Smith, J. (2026). Genetically Modified Microorganisms: Risks and Regulatory Considerations for Human and Environmental Health. Microorganisms, 14(2), 467. https://doi.org/10.3390/microorganisms14020467
  11. Liu, Y., et al. (2022). Genome editing technologies in bacteria: Advances and applications. Biotechnology Advances, 54, 107826.
  12. Mimee, M., Citorik, R. J., & Lu, T. K. (2016). Microbiome therapeutics—Advances and challenges. Advanced Drug Delivery Reviews, 105, 44–54. https://doi.org/10.1016/j.addr.2016.04.009
  13. Morais, L. H., Schreiber, H. L., & Mazmanian, S. K. (2021). The gut microbiota–brain axis in behaviour and brain disorders. Nature Reviews Microbiology, 19(4), 241–255. https://doi.org/10.1038/s41579-020-00460-0
  14. Pedrolli, D. B., Ribeiro, N. V., Squizato, P. N., de Jesus, V. N., Cozetto, D. A., & Teschke, O. (2019). Engineering microbial living therapeutics: The synthetic biology toolbox. Trends in Biotechnology, 37(1), 100–115. https://doi.org/10.1016/j.tibtech.2018.09.002
  15. Pickar-Oliver, A., & Gersbach, C. A. (2019). The next generation of CRISPR–Cas technologies and applications. Nature Reviews Molecular Cell Biology, 20(8), 490–507. https://doi.org/10.1038/s41580-019-0131-5
  16. Riglar, D. T., & Silver, P. A. (2018). Engineering bacteria for diagnostic and therapeutic applications. Nature Reviews Microbiology, 16(4), 214–225. https://doi.org/10.1038/nrmicro.2017.172
  17. Schmidt, M., & de Lorenzo, V. (2016). Synthetic constructs in/for the environment: Managing the interplay between natural and engineered biology. FEBS Letters, 590(20), 3832–3846. https://doi.org/10.1002/1873-3468.12377
  18. Smanski, M. J., et al. (2020). Synthetic biology to access and expand nature’s chemical diversity. Nature Reviews Microbiology, 18(3), 135–147.
  19. Steidler, L., & Rottiers, P. (2006). Therapeutic drug delivery by genetically modified Lactococcus lactis. Annals of the New York Academy of Sciences, 1072(1), 176–186. https://doi.org/10.1196/annals.1326.010
  20. Wang, H., & Qi, L. S. (2019). Synthetic RNA-based regulators in gene circuits. Nature Reviews Genetics, 20(5), 247–262. https://doi.org/10.1038/s41576-019-0101-3
  21. Wexler, H. M., & Goodman, A. L. (2017). An insider’s perspective: Bacteroides as a window into the microbiome. Nature Reviews Microbiology, 15(11), 697–710. https://doi.org/10.1038/nrmicro.2017.96
  22. Whitaker, W. R., Shepherd, E. S., & Sonnenburg, J. L. (2017). Engineering the gut microbiome with CRISPR–Cas systems. Nature Communications, 8, 15319. https://doi.org/10.1038/ncomms15319
  23. Zalila-Kolsi, I. (2025). Engineered bacteria as living therapeutics: Next-generation precision tools for health, industry, environment, and agriculture. AIMS Microbiology, 11(4), 946–962. https://doi.org/10.3934/microbiol.2025042
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