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  • Review Article
  • Published:

Emerging biomedical applications of synthetic biology

Nature Reviews Genetics volume 13, pages 21–35 (2012)Cite this article

Subjects

Key Points

  • A decade after the report of the first devices, synthetic biology has developed into an engineering science that provides novel opportunities to understand, diagnose, prevent and treat diseases.

  • Chemical synthesis and reconstruction of extinct or difficult-to-propagate viral genomes improves our understanding of virulence factors.

  • The de novo synthesis of deoptimized viral genomes enables the production of safe life vaccines.

  • Engineering environmentally responsive dominant-lethal genetic circuits into disease-transmitting insects provides a highly specific approach for controlling disease propagation.

  • The reconstruction of bacterial resistance circuits in mammalian cells enables the integrated discovery of agents to overcome resistance.

  • Engineered bacteria and synthetic genetic circuits that specifically detect and destroy neoplastic cells will provide momentum to future cancer therapies.

  • Molecular prostheses that detect disease states and autonomously trigger a therapeutic response in a closed-loop control configuration provide novel opportunities in the treatment of genetic and acquired diseases.

  • Synthetic gene circuits will provide novel opportunities for future gene and cell-based therapies.

Abstract

Synthetic biology aims to create functional devices, systems and organisms with novel and useful functions on the basis of catalogued and standardized biological building blocks. Although they were initially constructed to elucidate the dynamics of simple processes, designed devices now contribute to the understanding of disease mechanisms, provide novel diagnostic tools, enable economic production of therapeutics and allow the design of novel strategies for the treatment of cancer, immune diseases and metabolic disorders, such as diabetes and gout, as well as a range of infectious diseases. In this Review, we cover the impact and potential of synthetic biology for biomedical applications.

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Figure 1: Mammalian gene expression control strategies.
Figure 2: Synthetic biology for understanding and preventing disease.
Figure 3: Mammalian-cell-based drug discovery.
Figure 4: Drug delivery.
Figure 5: Bacterial and viral cancer therapy.
Figure 6: Synthetic genetic cancer classifiers.
Figure 7: Advanced therapeutic and prosthetic networks.

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Acknowledgements

Work in the laboratory of W.W. is supported by the European Research Council (ERC) under the European Community's Seventh Framework Programme (FP7/2007-2013) ERC Grant agreement number 259043-CompBioMat and the Excellence Initiative of the German Federal and State Governments (EXC 294). Work in the laboratory of M.F. is supported by the Swiss National Science Foundation (grant number 3100A0-112549) and in part by the European Community Framework 7 (Persist).

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Authors and Affiliations

  1. Faculty of Biology, University of Freiburg, Schänzlestrasse 1, Freiburg, D-79104, Germany

    Wilfried Weber

  2. BIOSS Centre for Biological Signalling Studies, University of Freiburg, Hebelstrasse 25, Freiburg, D-79104, Germany

    Wilfried Weber

  3. Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, Basel, CH-4058, Switzerland

    Martin Fussenegger

  4. Faculty of Science, University of Basel, Mattenstrasse 26, Basel, CH-4058, Switzerland

    Martin Fussenegger

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  1. Wilfried Weber
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  2. Martin Fussenegger
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Correspondence to Martin Fussenegger.

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Glossary

Aptamer

An oligonucleic acid that binds to a specific target, such as a chemical compound, a protein or a nucleic acid. Aptamers were found to control riboswitches in natural systems, but they can also be selected in vitro.

Epigenetic toggle switches

Genetic circuits that can be switched between two stable expression states (for example, an 'on' and an 'off' state) by a transient stimulus. In the absence of a switching stimulus, the expression state is locked and inherited across cell generations.

Hysteretic circuits

Genetic circuits whose response dynamics depend on a combination of past and present states.

Eco-sensing

The capacity of a species to sense and score its surrounding ecosystem, for example, to identify the type and population density of neighbouring species.

Quorum sensing

A small-molecule-based chemical language by which bacteria communicate within and across populations (the 'quorum'). Production and response to quorum-sensing molecules is correlated with population density.

Band-pass filters

These are devices that are selectively induced within a specific concentration range of the input signal. At lower or higher trigger levels, the band-pass filter shuts down output signals.

Immunostimulatory liposomes

Liposomes that are decorated with antigenic peptides or proteins that elicit an immune response.

Gene drive system

These are molecular devices that promote the spreading of a specific gene throughout a target population by taking advantage of a mechanism that multiplies the specific gene in the host genome. Gene drive systems produce non-Mendelian patterns of inheritance.

Polyketides

These constitute a group of secondary metabolites produced through linear decarboxylative condensation of acetyl-CoA with several malonyl-CoA-derived extender units to a polyketide chain. Many pharmacologically active compounds, such as antibiotics and anti-cancer drugs, belong to the polyketide class.

SOS DNA repair

Genetically encoded repair program protecting against DNA damage. In prokaryotes, the repair program is coordinated by LexA and RecA.

Persister cells

Dormant individual cells within a bacterial population that show a high tolerance to antimicrobials.

Pharmacokinetics

The action of drugs in the body over a period of time. It covers absorption of the drug as well as its distribution, tissue localization, biotransformation and excretion.

Commensal bacteria

Commensal bacteria live in close contact with the host. In this special type of symbiosis, one partner is benefited, whereas the other is neither benefited nor harmed.

Melanopsin

A vitamin-A-dependent, G-protein-coupled receptor that is expressed in intrinsically photosensitive retinal ganglion cells

Prosthetic networks

Networks that replace existing cellular functionality that is ill-driven or out of order. They represent molecular prostheses for non-functional cellular activity; they differ from other synthetic networks that add useful functionality but do not replace non-functional cellular networks.

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Weber, W., Fussenegger, M. Emerging biomedical applications of synthetic biology. Nat Rev Genet 13, 21–35 (2012). https://doi.org/10.1038/nrg3094

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