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  • Review Article
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Synthetic gene circuits for the detection, elimination and prevention of disease

Nature Biomedical Engineering volume 2, pages 399–415 (2018)Cite this article

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Abstract

In living organisms, naturally evolved sensors that constantly monitor and process environmental cues trigger corrective actions that enable the organisms to cope with changing conditions. Such natural processes have inspired biologists to construct synthetic living sensors and signalling pathways, by repurposing naturally occurring proteins and by designing molecular building blocks de novo, for customized diagnostics and therapeutics. In particular, designer cells that employ user-defined synthetic gene circuits to survey disease biomarkers and to autonomously re-adjust unbalanced pathological states can coordinate the production of therapeutics, with controlled timing and dosage. Furthermore, tailored genetic networks operating in bacterial or human cells have led to cancer remission in experimental animal models, owing to the network’s unprecedented specificity. Other applications of designer cells in infectious, metabolic and autoimmune diseases are also being explored. In this Review, we describe the biomedical applications of synthetic gene circuits in major disease areas, and discuss how the first genetically engineered devices developed on the basis of synthetic-biology principles made the leap from the laboratory to the clinic.

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Fig. 1: Development process for gene circuits addressing medical conditions.
Fig. 2: Diagnostic circuits for detecting disease.
Fig. 3: Treating disease with therapeutic gene circuits.
Fig. 4: Genetic control networks as anti-infectives.
Fig. 5: Biocomputation to identify disease patterns.
Fig. 6: Preventive disease control by microencapsulated designer cells.

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Acknowledgements

We thank D. Fuchs, D. Sequeira, X. Pierrat and S. Ausländer for scientific advice. This work was supported by a European Research Council Advanced Grant (ProNet, no. 321381).

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Authors and Affiliations

  1. Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland

    Ferdinand Sedlmayer & Martin Fussenegger

  2. IUTA Département Génie Biologique, Université Claude Bernard Lyon 1, Lyon, France

    Dominique Aubel

  3. Faculty of Science, University of Basel, Basel, Switzerland

    Martin Fussenegger

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  1. Ferdinand Sedlmayer
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  2. Dominique Aubel
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  3. Martin Fussenegger
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Correspondence to Martin Fussenegger.

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Sedlmayer, F., Aubel, D. & Fussenegger, M. Synthetic gene circuits for the detection, elimination and prevention of disease. Nat Biomed Eng 2, 399–415 (2018). https://doi.org/10.1038/s41551-018-0215-0

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