ArticleNucleic acids research2019
Fail-safe genetic codes designed to intrinsically contain engineered organisms.
Article in Nucleic acids research, 2019. 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 21 papers.
What it found
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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.
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.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Biological Systems as Physical Data Processors: Evolution as a Case of Embodied Computing.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Structural adaptations for enhanced translation kinetics in evolved ribosomes.Nucleic acids research · 2026Article
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- Structural adaptations for enhanced translation kinetics in evolved ribosomes.bioRxiv : the preprint server for biology · 2026Article
- Simultaneous in vitro expression of minimal 21 transfer RNAs by tRNA array method.Nature communications · 2025Article
- The design and engineering of synthetic genomes.Nature reviews. Genetics · 2025Review
- Cell-Free Gene Expression: Methods and Applications.Chemical reviews · 2025Review
- Robust genetic codes enhance protein evolvability.PLoS biology · 2024Article
- Strategies to identify and edit improvements in synthetic genome segments episomally.Nucleic acids research · 2023Article
- Engineering tRNA abundances for synthetic cellular systems.Nature communications · 2023Article
- Mutation bias and the predictability of evolution.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Stability, robustness, and containment: preparing synthetic biology for real-world deployment.Current opinion in biotechnology · 2023Review
- Refactored genetic codes enable bidirectional genetic isolation.Science (New York, N.Y.) · 2022Article
- Environmental Galenics: large-scale fortification of extant microbiomes with engineered bioremediation agents.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Review
- Overlapping genes in natural and engineered genomes.Nature reviews. Genetics · 2022Review
- Codon-Reduced Protein Synthesis With Manipulating tRNA Components in Cell-Free System.Frontiers in bioengineering and biotechnology · 2022Review
- Engineering Posttranslational Regulation of Glutamine Synthetase for Controllable Ammonia Production in the Plant Symbiont Azospirillum brasilense.Applied and environmental microbiology · 2021Article
- Reconstituted cell-free protein synthesis using in vitro transcribed tRNAs.Communications biology · 2020Article
- Growing a circular economy with fungal biotechnology: a white paper.Fungal biology and biotechnology · 2020Review
- Emerging Methods for Efficient and Extensive Incorporation of Non-canonical Amino Acids Using Cell-Free Systems.Frontiers in bioengineering and biotechnology · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One challenge in engineering organisms is taking responsibility for their behavior over many generations. Spontaneous mutations arising before or during use can impact heterologous genetic functions, disrupt system integration, or change organism phenotype. Here, we propose restructuring the genetic code itself such that point mutations in protein-coding sequences are selected against. Synthetic genetic systems so-encoded should fail more safely in response to most spontaneous mutations. We designed fail-safe codes and simulated their expected effects on the evolution of so-encoded proteins. We predict fail-safe codes supporting expression of 20 or 15 amino acids could slow protein evolution to ∼30% or 0% the rate of standard-encoded proteins, respectively. We also designed quadruplet-codon codes that should ensure all single point mutations in protein-coding sequences are selected against while maintaining expression of 20 or more amino acids. We demonstrate experimentally that a reduced set of 21 tRNAs is capable of expressing a protein encoded by only 20 sense codons, whereas a standard 64-codon encoding is not expressed. Our work suggests that biological systems using rationally depleted but otherwise natural translation systems should evolve more slowly and that such hypoevolvable organisms may be less likely to invade new niches or outcompete native populations.
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Registered trials
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.