In a groundbreaking development, researchers have successfully modified a strain of Escherichia coli (E. coli) bacteria to be virtually immune to all known viral infections. This breakthrough has the potential to reduce the risk of viral contamination in bacterial biofactories, which are responsible for producing essential substances like insulin and biofuels.
The research team, led by first author Akos Nyerges, a research fellow in genetics at the Blavatnik Institute at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering, claims to have developed the first technology capable of designing an organism that is immune to any known virus. While they cannot guarantee complete immunity, their extensive laboratory experiments and computational analysis have not found a virus capable of infecting the modified strain of E. coli.
This breakthrough builds upon previous efforts to create virus-resistant bacteria. In 2022, a group from the University of Cambridge claimed to have developed an E. coli strain immune to viruses. However, when Nyerges and his colleagues tested this claim, they found that the modified bacteria could still be easily infected by viruses collected from various environments, such as chicken sheds, rat nests, and sewage.
The Cambridge team’s approach involved reducing the number of codons in E. coli from 64 to 61, with the idea that without the missing codons, viruses would not be able to hijack an organism’s cells. However, the method proved imperfect, and some viruses were still able to infect the cells.
To further enhance the virus resistance, the Harvard researchers not only deleted codons but also introduced a specific type of RNA called transfer RNA (tRNA). These modified tRNAs effectively sabotaged viral protein production by adding the wrong amino acids, resulting in misfolded, non-functional viral proteins. This prevented the virus from replicating and infecting more cells.
While viruses could theoretically mutate to overcome the swapped codons and tRNAs, Nyerges explained that this would require dozens of highly specific mutations simultaneously, making it “very, very unlikely for natural evolution.”
To prevent these genetically modified organisms (GMOs) from escaping into the wild and causing potential harm, the researchers implemented two major safeguards. First, if another organism encounters the modified E. coli and receives the trickster tRNAs, the misreading of serine codons will damage or kill the recipient cell, stopping further spread. Second, the modified E. coli is entirely dependent on lab-made amino acids unavailable in the wild, ensuring they cannot survive outside of controlled environments.
The technique developed by the researchers could have significant implications for biocontainment strategies and GMO development. The virus-resistant bacteria could be used to produce valuable substances without the risk of viral contamination, and the technology could also improve the safety of genetically modified crops, reducing the spread of disease and potentially increasing food security.
Journal. A swapped genetic code prevents viral infections and gene transfer