SBIR Phase II: A Platform for Anthelmintic Drug Discovery using Genome-modified C. elegans

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is the development of a platform for the discovery of new anthelmintic (anti-parasite) drugs. Drug resistance is occurring with all anthelmintics currently on the market. Current drug development only introduces new molecules to the existing drug targets. As a result, drug resistance quickly jumps to these new drugs, which makes them ineffective shortly after market introduction. Without an adequate source of effective anthelmintics, livestock yields, crop damage, and human capital are starting to suffer. The social burden is creating economic losses totaling hundreds of billions of dollars worldwide. By focusing on a novel drug target that controls entry into infective life forms, this proposal aims to generate a new class of anthelmintics to combat this growing problem. The drug companies that commercialize this potential new class of anthelmintics will access a market potential of $1.5 B per year or more. The SBIR Phase II project proposes to develop a platform for the discovery of new anthelmintic drugs using genetically engineered nematods (C. elegans). The approach used will insert a segment of a parasite gene in replacement of a segment of a native gene. The resulting chimera gene converts the C. elegans nematode into a form that better mimics the parasite state. Drug hits found active on the chimera-expressing nematode are then refined into leads by testing for efficacy against parasite infection model. The proposal's chimera platform is adapted to a diverse set of parasite genes. The resulting diverse platform is expected to provide a rapid path to discovery and eventual introduction of a novel class of anti-parasite drugs with broad-spectrum activity.