EAGER: Evolutionary design of protease substrate specificity

University Of California-Santa Barbara, Santa Barbara CA

Investigators

Abstract

The goal of this EAGER award is to develop a new and potentially transformative technology to enable the rapid development of secreted proteases with extended substrate specificity. These proteases would constitute a new class of therapeutics that could be used to treat certain diseases where overproduction of a protein, or production of a poorly folded protein leads to the disease state. As evidenced by the therapeutic use of botulinum toxin, the ability to achieve precise specificity towards an arbitrary target would dramatically reduce the production costs of biological theraputics by orders of magnitude, when compared to therapeutic antibodies. Although a few proteases have proven to be effective therapeutics, their use has been limited because of the inability to engineer proteases with desired specificity. To address this need, a novel proteases library screening technology will be developed to enable multi step directed evolution of protease specificity. The technology will be tested in a target application for Alzheimer's disease.