Enabling Drug Discovery for Malaria

Agave BioSystems has been highly successful in accomplishing the Phase I objectives. In this Phase II proposal, Agave BioSystems will build upon the results generated in the Phase I to isolate additional shikimate pathway genes. We will continue to usestate-of-the-art-bioinformatics computational analysis to assist in identifying genes in this pathway. We will also continue our use of both genetic and functional approaches for gene isolation. The genes for these enzymes will then be cloned into aheterologous system such as E. coli so that the enzymes can be overexpressed and purified. Additionally, rapid, highly sensitive biochemical assays for these enzymes will be developed for screening of potential drug libraries. The development of methodsfor identifying and isolating genes from Plasmodium, as well as biochemical assays for the shikimate pathway genes, will greatly enhance the rate at which drugs can be screened for potential anti-malarial activity. As a result of the successful completionof both the Phase I and Phase II programs, Agave BioSystems will have established the core technology to validate genes isolated from a particular group of organisms and express and isolate them in recombinant form to enable drug discovery. This processcan then be used to develop drugs for other significant pathogens.The import of the information is reflected in the prevalence and mortality resulting from malaria (300 million cases, 1 million deaths per year). Thus, the commercial value of any information that could serve as the foundation for anti-malarial drugdevelopment is extremely high. Organizations that could benefit from this Phase I project include not only pharmaceutical companies, but also federal agencies and international organizations engaged in fighting tropical illnesses.