# Genetic Code-Locking Confers Stable Virus Resistance to a Recoded Organism

**Authors:** Jérôme F. Zürcher, Alexandre Dickson, Tomás Kappes, Askar A. Kleefeldt, Kim C. Liu, George P. C. Salmond, Jason W. Chin

PMC · DOI: 10.1021/acs.biochem.5c00075 · Biochemistry · 2025-07-01

## TL;DR

Changing the genetic code in an organism can temporarily protect it from viruses, but this protection is only stable if the new code is locked in.

## Contribution

The study shows that locking in a refactored genetic code is essential for long-term virus resistance.

## Key findings

- Refactoring the genetic code alone provides temporary resistance to viruses.
- Unlocked refactored codes can revert, causing loss of resistance.
- Code-locking is crucial for stable, long-term resistance against viral infections.

## Abstract

The genetic code defines the correspondence between codons
in genes
and amino acids in proteins. Reassignment of sense codons to different
amino acids can create cells with refactored genetic codes that are
distinct from the canonical genetic code. By encoding essential genes
according to the refactored genetic code, this code becomes locked-in,
making it essential to the host cell. Here, we show that refactoring
the structure of the genetic code alone is sufficient to confer temporary
resistance to complex mobile genetic elements, such as viruses. However,
when the refactored genetic code is not locked-in, it can revert,
leading to loss of resistance. Thus, locking the refactored genetic
code may be crucial for maintaining stable, long-term resistance in
the face of sporadic and unpredictable viral infection.

## Full-text entities

- **Diseases:** viral infection (MESH:D014777)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12269064/full.md

## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12269064/full.md

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Source: https://tomesphere.com/paper/PMC12269064