Viruses Show Promise for Creating Drugs By Doing What They Do Best: Evolving
Test-tube evolution just went viral: a new study shows how to use viruses’ knack for natural selection to create tailored proteins. Researchers at Harvard say their new technique is a hundred times faster than the usual methods, churning through 200 generations of proteins in 8 days, and, crucially, requires no attention from researchers after itâ€™s set up: a crock pot for evolution. Though a godsend primarily for researchers, in the future it could accelerate the growth of customized proteins for new drugs.
How the Heck:
- Researchers first set up a container with a constant flow of fluid and cells and then add viruses, which start to infect the cells. The viruses carry the genes for a protein researchers want to optimize—for instance, a partially effective drug they want to improve.
- The proteins spring into action, snipping or changing whatever other molecules researchers might want them to act on. (This might be something like cholera toxins or oil molecules added to the fluid, or it could be a molecule naturally present in the cell.) As the proteins work, they also activate the transcription of the gene that allows the virus to make more copies of itself.
- Speed is key: a protein has to work above a certain rate or the virus won’t become infectious in time to take over new cells and avoid being flushed out. Thus, if a candidate protein doesn’t work fast enough to keep its virus infectious, it gets literally flushed out of the gene pool by fluid draining out of the container.
- To create a bunch of new and possible faster varieties, a chemical in the fluid mutates the proteins, and the cycle repeats. At the end, the only proteins left are the fastest at their appointed task—and therefore the fittest.
Whatâ€™s the Context:
- Recapitulating evolution in a test tube to make tailored moleculesâ€”â€œdirected evolutionâ€â€”arrived on the scene in the early 1990s. It draws on the idea that if exposed to tough new environments, cells will evolve proteins and other biomolecules that enable them to surviveâ€”for instance, enzymes that can fight infections or digest oil spills. Researchers can then harvest the evolved enzymes for their own purposes, which range from developing detergents (the first evolved product on the market was a stain-munching enzyme) to treating cancer.
- Most techniques take a lot of work: researchers insert the DNA for hundreds or thousands of candidate proteins into cells and watch to see which succeed, manually removing the candidates that don’t help the cell grow faster or eat stains better. Then they cause small mutations in the DNA, to introduce genetic variety, and repeat the cycle. Much of this process can now be done easily by machines, except for the selection step, which is where the Harvard team made their improvement.
Reference: Esvelt et al. A system for the continuous directed evolution of biomolecules. Nature. doi:10.1038/nature09929.
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