Scientists engineer safe, virus-resistant E coli for research

Genetically engineering virus in the lab

In a step forward for genetic engineering and synthetic biology, US researchers have modified E coli bacteria to be immune to infection by all natural viruses tested so far.

The team used two safeguard methods to prevent the bacteria and their modified genes from escaping into the wild.

The work promises to reduce the threats of viral contamination when harnessing bacteria to produce medicines such as insulin as well as other useful substances, such as biofuels.

Currently, viruses that infect vats of bacteria can halt production, compromise drug safety, and cost millions of dollars.

“We believe we have developed the first technology to design an organism that can’t be infected by any known virus,” said the study’s first author, Akos Nyerges, research fellow in genetics in the lab of George Church in the Blavatnik Institute at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering.

“We can’t say it’s fully virus-resistant, but so far, based on extensive laboratory experiments and computational analysis, we haven’t found a virus that can break it.”

Genetic engineering

The findings build on earlier efforts by genetic engineers, which involved genetically reprogramming E. coli to make all their life-sustaining proteins from 61 sets of genetic building blocks, or codons, instead of the naturally occurring 64.

The HMS team figured out that the key lay in transfer RNAs (tRNAs). Each tRNA’s role is to recognise a specific codon and add the corresponding amino acid to a protein that’s being built. For instance, the codon TCG tells its matching tRNA to attach the amino acid serine.

The HMS researchers added new, ‘trickster’ tRNAs, which add leucine instead of serine. Inserting the wrong amino acids results in misfolded, non-functional viral proteins.

“It was very challenging and a big achievement to demonstrate that it’s possible to swap an organism’s genetic code,” said Nyerges, “and that it only works if we do it this way.”

Two safeguards

The work incorporates two separate safeguards. The first protects against horizontal gene transfer, a constantly occurring phenomenon in which snippets of genetic code and their accompanying traits, such as antibiotic resistance, get transferred from one organism to another.

For the second fail-safe, the team made the bacteria themselves incapable of living outside a controlled environment. Therefore, no humans or other creatures are at risk of getting infected by “super-bacteria,” Nyerges emphasised.

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