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categories: ["genetics"]categories: ["genetics"]tags: ["synthetic biology", "genetic code", "protein engineering", "biocontainment", "virus resistance"]tags: ["synthetic biology", "genetic code", "protein engineering", "biocontainment", "virus resistance"]summary: "Altering how a cell reads DNA so that reassigned codons encode amino acids not found in nature, producing organisms with chemistry and immunity no natural cell has."summary: "Altering how a cell reads DNA so that reassigned codons encode amino acids not found in nature, producing organisms with chemistry and immunity no natural cell has."updated: "2026-07-27"updated: "2026-08-23"humanEvidence: "No recoded mammal or person exists; genome recoding has been demonstrated only in bacteria, and the nearest contact with patients is investigational antibody conjugates built using non-standard amino acids."humanEvidence: "No recoded mammal or person exists; genome recoding has been demonstrated only in bacteria, and the nearest contact with patients is investigational antibody conjugates built using non-standard amino acids."access: "Not a clinical or consumer technology: recoded strains exist in a handful of academic laboratories, and the only products near patients are investigational antibody conjugates."access: "Not a clinical or consumer technology: recoded strains exist in a handful of academic laboratories, and the only products near patients are investigational antibody conjugates."reversibility: "irreversible"reversibility: "irreversible"lines 66–71 → 66–7551 unchanged lines not shown
Recoding at genome scale exists only in bacteria. Code expansion — adding one or two non-standard amino acids without clearing their codons — works routinely in yeast, in cultured mammalian cells, and in whole animals including mice, where it is used to make proteins that can be switched on with light or cross-linked to their binding partners on command. No recoded mammalian genome exists, and none is close: the recoding of a bacterial genome required total synthesis of four megabases, and a human genome is close to a thousand times that size.Recoding at genome scale exists only in bacteria. Code expansion — adding one or two non-standard amino acids without clearing their codons — works routinely in yeast, in cultured mammalian cells, and in whole animals including mice, where it is used to make proteins that can be switched on with light or cross-linked to their binding partners on command. No recoded mammalian genome exists, and none is close: the recoding of a bacterial genome required total synthesis of four megabases, and a human genome is close to a thousand times that size. > [!caution] The eukaryotic case is half a recoding> Yeast is where the two halves of recoding come apart, and it is worth stating which half is done. The Sc2.0 design changes every TAG stop codon in the genome to TAA, and all sixteen synthetic chromosomes have now been built to it,[^richardson2017] so the rewriting half exists in a eukaryote. The freeing half does not: eukaryotic release factor eRF1 reads all three stop codons, so it cannot be deleted the way bacterial RF1 was once its codon was cleared, and re-engineering it to ignore TAG remains a proposal.> The chromosomes are also still in separate strains. The largest consolidated strain reported carries seven and a half of them, rather more than half the genome, and combining the rest into one cell is the project's stated open problem.[^zhao2023] Until that strain exists and its eRF1 is altered, genome-scale recoding in a eukaryote is a design that has been printed, not a code that has been changed. The commercial application that reached medicine first is protein conjugation. Placing a non-standard amino acid with a chemically distinct handle at a chosen position in an antibody allows a drug payload to be attached at exactly that site and nowhere else, giving a homogeneous product rather than the mixture produced by conventional chemistry. Antibody–drug conjugates built this way have advanced through clinical development, and the approach is now one of the more mature strands of [[targeted-drug-delivery]].The commercial application that reached medicine first is protein conjugation. Placing a non-standard amino acid with a chemically distinct handle at a chosen position in an antibody allows a drug payload to be attached at exactly that site and nowhere else, giving a homogeneous product rather than the mixture produced by conventional chemistry. Antibody–drug conjugates built this way have advanced through clinical development, and the approach is now one of the more mature strands of [[targeted-drug-delivery]]. ## Limitations## Limitationslines 107–110 → 111–11635 unchanged lines not shown
[^fredens2019]: `paper` Fredens, J. et al. "Total synthesis of Escherichia coli with a recoded genome." *Nature*, 2019.[^fredens2019]: `paper` Fredens, J. et al. "Total synthesis of Escherichia coli with a recoded genome." *Nature*, 2019.[^robertson2021]: `paper` Robertson, W. E. et al. "Sense codon reassignment enables viral resistance and encoded polymer synthesis." *Science*, 2021.[^robertson2021]: `paper` Robertson, W. E. et al. "Sense codon reassignment enables viral resistance and encoded polymer synthesis." *Science*, 2021.[^nyerges2023]: `paper` Nyerges, A. et al. "A swapped genetic code prevents viral infections and gene transfer." *Nature*, 2023.[^nyerges2023]: `paper` Nyerges, A. et al. "A swapped genetic code prevents viral infections and gene transfer." *Nature*, 2023.[^richardson2017]: `paper` Richardson, S. M., Mitchell, L. A., Stracquadanio, G. et al. "Design of a synthetic yeast genome." *Science*, 2017. {A specification rather than a built strain: it sets out the TAG-to-TAA change and the other Sc2.0 design rules, and the chromosomes were synthesized to it over the following eight years.}[^zhao2023]: `paper` Zhao, Y. et al. "Debugging and consolidating multiple synthetic chromosomes reveals combinatorial genetic interactions." *Cell*, 2023. {Reports the syn7.5 strain, which crosses half the genome; it does not report a strain carrying all sixteen synthetic chromosomes.} removed, struck through added, underlinedLine numbers count the serialised markdown of each revision, frontmatter included.
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