CAMBRIDGE, Mass. -- Scientists at Harvard University have harnessed the prowess of fast-replicating bacterial viruses, also known as phages, to accelerate the evolution of biomolecules in the laboratory. The work, reported this week in the journal Nature, could ultimately allow the tailoring of custom pharmaceuticals and research tools from lab-grown proteins, nucleic acids, and other such compounds.
The researchers, led by Professor David R. Liu, say their approach -- dubbed phage-assisted continuous evolution, or PACE -- is roughly 100 times faster than conventional laboratory evolution, and far less labor-intensive for scientists.
"Most modern drugs are based on small organic molecules, but biological macromolecules may be better suited as pharmaceuticals in some cases," says Liu, a professor of chemistry and chemical biology at Harvard and an investigator with the Howard Hughes Medical Institute. "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."
Liu and Harvard co-authors Kevin M. Esvelt and Jacob C. Carlson achieved up to 60 rounds of protein evolution every 24 hours by linking laboratory evolution to the life cycle of a virus that infects bacteria. This phage's life cycle of just 10 minutes is among the fastest known. Because this generation time is so brief, the phage makes a perfect vehicle for accelerated protein evolution. The PACE system uses E. coli host cells to produce the resulting proteins, to serve as factories for phage production, and to perform the key selection step that allows phage-carrying genes encoding desired molecules to flourish.
In three separate protein evolution experiments, PACE was able to generate an enzyme with a new target activity within a week, achieving up to 200 rounds of protein evolution during that time. Conventional la
|Contact: Michael Rutter|