Biocontainment of genetically modified organisms by synthetic protein design

Daniel J. Mandell, Marc J. Lajoie, Michael T. Mee, Ryo Takeuchi, Gleb Kuznetsov, Julie E. Norville, Christopher J. Gregg, Barry L. Stoddard and George M. Church ()
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Daniel J. Mandell: Harvard Medical School
Marc J. Lajoie: Harvard Medical School
Michael T. Mee: Harvard Medical School
Ryo Takeuchi: Fred Hutchinson Cancer Research Center
Gleb Kuznetsov: Harvard Medical School
Julie E. Norville: Harvard Medical School
Christopher J. Gregg: Harvard Medical School
Barry L. Stoddard: Fred Hutchinson Cancer Research Center
George M. Church: Harvard Medical School

Nature, 2015, vol. 518, issue 7537, 55-60

Abstract: Abstract Genetically modified organisms (GMOs) are increasingly deployed at large scales and in open environments. Genetic biocontainment strategies are needed to prevent unintended proliferation of GMOs in natural ecosystems. Existing biocontainment methods are insufficient because they impose evolutionary pressure on the organism to eject the safeguard by spontaneous mutagenesis or horizontal gene transfer, or because they can be circumvented by environmentally available compounds. Here we computationally redesign essential enzymes in the first organism possessing an altered genetic code (Escherichia coli strain C321.ΔA) to confer metabolic dependence on non-standard amino acids for survival. The resulting GMOs cannot metabolically bypass their biocontainment mechanisms using known environmental compounds, and they exhibit unprecedented resistance to evolutionary escape through mutagenesis and horizontal gene transfer. This work provides a foundation for safer GMOs that are isolated from natural ecosystems by a reliance on synthetic metabolites.

Date: 2015
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DOI: 10.1038/nature14121

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