Evidence map›Paper›PMID 25607366›Full record

ArticleNature2015

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, George M Church

Erratum issuedAbstract read
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 219 papers.

0numbers the graph read from it
0cells of the map it votes in
219citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

219 citing papers in PubMed.

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159 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Daniel J MandellDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Marc J Lajoie1] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Program in Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Michael T Mee1] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
Ryo TakeuchiDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Gleb KuznetsovDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Julie E NorvilleDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Christopher J GreggDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Barry L StoddardDivision of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
George M Church1] Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA.

Funding

Structure, function &engineering of nuclease catalystsR01GM049857 · NIGMS · FRED HUTCHINSON CANCER RESEARCH CENTER · PI STODDARD, BARRY L. · 1994 to 2014
$4.2M
Canadian Institutes of Health ResearchHoward Hughes Medical InstituteNIGMS NIH HHS R01 GM049857
6 · The paper itself

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.

Indexed as

Amino AcidsBiological EvolutionCodonContainment of BiohazardsEcosystemEscherichia coliEscherichia coli ProteinsGenes, EssentialGenetic CodeGenetic EngineeringGene Transfer, HorizontalMicrobial ViabilityMutationOrganisms, Genetically ModifiedSafetySelection, GeneticAmino AcidsCodonEscherichia coli Proteins

Identifiers

PMID25607366
PMCPMC4422498

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.