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Next-generation biocontainment systems for engineered organisms

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Abstract

The increasing use of engineered organisms for industrial, clinical, and environmental applications poses a growing risk of spreading hazardous biological entities into the environment. To address this biosafety issue, significant effort has been invested in creating ways to confine these organisms and transgenic materials. Emerging technologies in synthetic biology involving genetic circuit engineering, genome editing, and gene expression regulation have led to the development of novel biocontainment systems. In this perspective, we highlight recent advances in biocontainment and suggest a number of approaches for future development, which may be applied to overcome remaining challenges in safeguard implementation.

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Fig. 1: Biocontainment research timeline.
Fig. 2: Biocontainment through auxotrophy.
Fig. 3: Biocontainment using synthetic gene circuits.
Fig. 4: Orthogonal translation to confine transgenic functions.
Fig. 5: Unnatural nucleotides prevent access to transgenic information.

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Acknowledgements

We thank E. Cameron for his critical review and editing of the manuscript. The work was supported by the Wyss Institute for Biologically Inspired Engineering, the Paul G. Allen Frontiers Group, the Defense Threat Reduction Agency grant HDTRA1-14-1-0006, and Air Force Office of Scientific Research grant FA9550-14-1-0060. J.W.L. was also supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2018R1C1B3007409), and by the Marine Biotechnology Program (Marine BioMaterials Research Center) funded by the Ministry of Oceans and Fisheries, Korea. C.T.Y.C. was also supported by the University of Texas System Rising STARs Program and by the Welch Foundation (grant # BP-0037).

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  1. These authors contributed equally: Jeong Wook Lee, Clement T. Y. Chan.

Authors and Affiliations

  1. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA

    Jeong Wook Lee, Shimyn Slomovic & James J. Collins

  2. Department of Chemical Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea

    Jeong Wook Lee

  3. Institute for Medical Engineering & Science, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA

    Clement T. Y. Chan & James J. Collins

  4. Department of Biological Engineering, MIT, Cambridge, MA, USA

    Clement T. Y. Chan & James J. Collins

  5. Synthetic Biology Center, MIT, Cambridge, MA, USA

    Clement T. Y. Chan & James J. Collins

  6. Department of Biology, The University of Texas at Tyler, Tyler, TX, USA

    Clement T. Y. Chan

  7. Department of Chemistry and Biochemistry, The University of Texas at Tyler, Tyler, TX, USA

    Clement T. Y. Chan

  8. Harvard–MIT Program in Health Sciences and Technology, Cambridge, MA, USA

    James J. Collins

  9. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    James J. Collins

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Lee, J.W., Chan, C.T.Y., Slomovic, S. et al. Next-generation biocontainment systems for engineered organisms. Nat Chem Biol 14, 530–537 (2018). https://doi.org/10.1038/s41589-018-0056-x

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