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Nature. 2015 Feb 5;518(7537):55-60. doi: 10.1038/nature14121. Epub 2015 Jan 21.

Biocontainment of genetically modified organisms by synthetic protein design.

Author information

1
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
2
1] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Program in Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
3
1] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
4
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
5
1] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.

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.

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PMID:
25607366
PMCID:
PMC4422498
DOI:
10.1038/nature14121
[Indexed for MEDLINE]
Free PMC Article

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