“Swapped Genetic Code Blocks Viral Infections and Gene Transfer”, Akos Nyerges, Svenja Vinke, Regan Flynn, Sian 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. Church2022-07-10 (; backlinks)⁠:

Removing cellular transfer RNAs (tRNAs), making their cognate codons unreadable, creates a genetic firewall that prevents viral replication and horizontal gene transfer. However, numerous viruses and mobile genetic elements encode parts of the translational apparatus, including tRNAs, potentially rendering a genetic-code-based firewall ineffective.

In this paper, we show that such horizontally transferred tRNA genes can enable viral replication in Escherichia coli cells despite the genome-wide lack of 3 codons and the previously essential cognate tRNAs and release factor 1. By repurposing viral tRNAs, we then develop recoded cells bearing an amino-acid-swapped genetic code that reassigns two of the 6 serine codons to leucine during translation. This amino-acid-swapped genetic code renders cells completely 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.

Finally, we also repurpose the third free codon to biocontain this virus-resistant host via dependence on an amino acid not found in nature.

[previously: Robertson et al 2021 on virus-proofing]