Accelerating gene mutation

A method of reshaping complex biological molecules by “directing” evolution could lead to a host of new medicines, according to a US study.

The technique uses a virus that infects bacteria to accelerate the mutation rate of genes for therapeutic proteins.

Phage-assisted continuous evolution is said to be 100 times faster than conventional ways of producing large “macromolecules” such as enzymes that can fight disease.

Research leader David Liu, professor from Harvard University in Cambridge, Massachusetts, said: “Most modern drugs are based on small organic molecules, but biological macromolecules may be better suited as pharmaceuticals in some cases.

“Our work provides a new solution to one of the key challenges in the use of macromolecules as research tools or human therapeutics: how to rapidly generate proteins or nucleic acids with desired properties.”

The scientists used “phage” viruses to transfer evolving genes between a series of Escherichia coli bacteria.

At each step, the genes produce within the bacteria an altered version of the proteins they code for.

The virus has a life cycle of just 10 minutes, one of the fastest known. As a result, the researchers were able to achieve 60 rounds of protein evolution every 24 hours.

In three separate protein evolution experiments, Pace took less than a week to generate a novel enzyme, or biological catalyst. Up to 200 rounds of protein evolution were carried out during that time, a process that would normally take years.

Reporting their findings in the journal Nature, the research team wrote: “Laboratory evolution has generated many biomolecules with desired properties, but a single round of mutation, gene expression, screening or selection, and replication typically requires days or longer with frequent human intervention.”