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Protein design
Computational designs for proteins can be turned into molecular models like the one at left, or into actual molecules with medical applications. (Credit: UW Institute for Protein Design)

Synthetic genomes and gene editing are big things today, but the next big things in biotechnology could be proteins that are designed and edited on computers – and are then synthesized to produce novel types of medicines, materials and molecular machines.

“It’s the right time for this field,” David Baker, director of the University of Washington’s Institute for Protein Design, said Monday at the EXOME Life Science Disruptors conference. The event was presented by Xconomy at the Fred Hutchinson Cancer Research Center in Seattle.

Baker is a pioneer in protein design, going back to the invention of the Rosetta protein modeling software more than a decade ago. Rosetta spawned the Foldit video game, which has attracted hundreds of thousands of protein-folding players. It has also spawned a commercial spin-out known as Cyrus Biotechnology, which is turning Rosetta into a commercial-grade, cloud computing platform.

“We are currently doing projects with eight companies, have four companies about to start a paid beta test … and a growing wait list to enter the beta, currently two companies,” Cyrus Biotech CEO Lucas Nivón told GeekWire in an email. “The next big events on Cyrus’s horizon are the official launch of beta in mid-May, and the launch out of beta into initial release in the June/July time frame.”

Other startups are developing new drugs. PVP Biologics, for example, is tweaking proteins into pharmaceuticals that could counter celiac disease, an autoimmune disorder that has forced millions of Americans to swear off gluten.

“We took enzymes that already exist, then engineered them to alter their properties,” said Ingrid Swanson Pultz, a veteran of Baker’s lab who founded PVP Biologics. She’s now looking for industry partners to help get the company’s hybrid enzyme ready for clinical trials.

Another spin-out called Virvio is designing proteins from the ground up to stop flu viruses in their tracks by gumming up the molecular machinery. Virvio’s chief technical officer, Aaron Chevalier, told GeekWire that the company has 42,000 candidate proteins to sort through.

Designer proteins take advantage of the fact that the physical structures of molecules mesh with each other like keys fitting into locks. If the protein is folded correctly, it opens a lock in the cell and sets off a biological process. That’s how the engineered enzyme being developed by PVP Biologics could break down gluten in the stomach of a celiac patient, for instance.

On the flip side, viruses take advantage of the key-and-lock system to hijack normal cells. For example, a flu virus uses a “key” protein such as hemagglutinin to unlock the cellular doorway. Some researchers already have found chemical compounds that attach to the viral keys and render them useless. Chevalier and his colleagues at Virvio are looking for synthetic proteins that optimize the key-canceling effect.

It’s important that the proteins developed to fight the flu don’t have a negative effect on other cellular processes – for example, by shutting down a desired function or setting off an immune response. “Thus far, at least, with the influenza proteins it hasn’t been a problem,” Chevalier said.

Baker said designer proteins could take on a wide range of biochemical tasks, ranging from delivering encapsulated drugs, to serving as synthetic vaccines, to identifying and targeting cancer cells. Some of the molecules under development at the Institute for Protein Design can assemble themselves into regular structures.

The possibilities aren’t limited to medical applications. Synthetic proteins could also be used as a matrix for hybrid composite materials inspired by the mother-of-pearl interior of an abalone shell.

“We’re even trying to design a protein-based computing system,” Baker said.

Nanocomputers created from folded-up proteins? It may sound like one of the next big things for science-fiction writers, but the technology is already being tested.

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