A swapped genetic code prevents viral infections and gene transfer

Autor: Akos Nyerges, Svenja Vinke, Regan Flynn, Siân V. Owen, Eleanor A. Rand, Bogdan Budnik, Eric Keen, Kamesh Narasimhan, Jorge A. Marchand, Maximilien Baas-Thomas, Min Liu, Kangming Chen, Anush Chiappino-Pepe, Fangxiang Hu, Michael Baym, George M. Church
Rok vydání: 2023
Předmět:
Zdroj: Nature
ISSN: 1476-4687
0028-0836
DOI: 10.1038/s41586-023-05824-z
Popis: 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. In this paper, we show that such mobile transfer RNAs (tRNAs) enable gene transfer and allow viral replication in Escherichia coli despite the genome-wide removal of three 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 selective advantage over wild organisms due to virus-resistance, we also repurpose a third codon to biocontain this virus-resistant host via dependence on an amino acid not found in nature(10). Our results suggest 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.
Databáze: OpenAIRE
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