Our core technology consists of methods for rapidly identifying and characterizing proteases with altered specificity. These include a bioinformatics component for identifying potential targets and corresponding therapeutic protease candidates; a suite of protease scaffold domains; mutagenesis and expression technologies; profiling technology to measure protease specificity; and screens to select for novel, highly selective proteases. This core technology will enable the rapid identification of proteases that can inactivate any extracellular or membrane-associated protein target.

The figure below represents the process we use to create novel proteases that can cleave and inactivate a therapeutic target. Briefly, rational design and combinatorial mutagenesis are used to generate libraries of mutants. Mutants are profiled using combinatorial substrate libraries to determine the change in substrate specificity. The most promising mutants are tested for efficacy in both cell-based assays and animal models. If necessary (for example, when extremely stringent specificity is desired), this process can be used iteratively - mutants can be subjected to this process multiple times (i.e., "evolved") to obtain the desired activity and specificity. This core technology is amenable to automation and facilitates rapid identification of potential biopharmaceuticals.