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Journal Article
A swapped genetic code prevents viral infections and gene transfer
2023
Overview
Engineering the genetic code of an organism has been proposed to provide a firewall from natural ecosystems by preventing viral infections and gene transfer
1
–
6
. However, numerous viruses and mobile genetic elements encode parts of the translational apparatus
7
–
9
, potentially rendering a genetic-code-based firewall ineffective. Here we show that such mobile transfer RNAs (tRNAs) enable gene transfer and allow viral replication in
Escherichia coli
despite the genome-wide removal of 3 of the 64 codons and the previously essential cognate tRNA and release factor genes. We then establish a genetic firewall by discovering viral tRNAs that provide exceptionally efficient codon reassignment allowing us to develop cells bearing an amino acid-swapped genetic code that reassigns two of the six serine codons to leucine during translation. This amino acid-swapped genetic code renders cells resistant to viral infections by mistranslating viral proteomes and prevents the escape of synthetic genetic information by engineered reliance on serine codons to produce leucine-requiring proteins. As these cells may have a selective advantage over wild organisms due to virus resistance, we also repurpose a third codon to biocontain this virus-resistant host through dependence on an amino acid not found in nature
10
. Our results may provide the basis for a general strategy to make any organism safely resistant to all natural viruses and prevent genetic information flow into and out of genetically modified organisms.
A study details the creation of an
Escherichia coli
genetically recoded organism that is resistant to viral infection, and describes a further modification that keeps the organism and its genetic information biocontained.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 42/40
/ 42/44
/ 45/23
/ 631/337
/ 631/61
/ 82/58
/ 82/83
/ Codons
/ E coli
/ Gene Transfer, Horizontal - genetics
/ Genes
/ Genetically modified organisms
/ Genome, Bacterial - genetics
/ Genomes
/ Host Microbial Interactions - genetics
/ Humanities and Social Sciences
/ Leucine
/ Organisms, Genetically Modified - genetics
/ Plasmids
/ Protein Biosynthesis - genetics
/ Science
/ Serine
/ tRNA
/ Virus Diseases - prevention & control
/ Viruses
