Institute for Protein Design's de novo revolution

How a Seattle hub is overhauling protein- and cell-based therapies by breaking free of evolution's constraints.

Seattle's Institute for Protein Design is growing an army of spinouts that build proteins from the ground up. With applications ranging from multivalent vaccines and synthetic cytokines to precision cell therapies, these companies could put de novo designed proteins on the map and bring forth a new generation of biologics.

"If we're successful, then the whole way biologics are made could change a lot in the next ten years. But I think currently, we're kind of on the fringe," said David Baker, who directs University of Washington’s Institute for Protein Design (IPD) and is a professor of biochemistry and a Howard Hughes Medical Institute investigator.

IPD's core technology is Rosetta, a computational platform for modeling, predicting and designing protein structures.

Rosetta's lowest hanging fruit are in optimizing the structures of existing proteins. But the platform is increasingly being used for de novo protein design: making fit-for-purpose proteins that are completely unrelated to any proteins that have evolved in nature.

Using Rosetta, researchers can identify a structure corresponding to a desired function, then find an amino acid sequence that readily and stably folds into that structure because it is the lowest free energy state for that sequence.

"Almost all biologics design that's done is by selection. Either you identify a naturally occurring protein, or an antibody that you elicited in a mouse. There's almost no design based on things like the concept that proteins fold to the lowest energy state," Baker told BioCentury.

De novo protein design can tailor

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