The frequency of invasive Aspergillus-related disease is rapidly increasing worldwide and few effective treatments are available, thus the need for novel antifungals effective against Aspergillus is critical. A high-throughput screen for essential genes will be undertaken in Aspergillus fumigatus. The genes identified will be developed as new antifungal targets. An expression vector system suitable for screening libraries in Aspergillusfumigatus has been developed. Phase I of this project includes modification and optimization of the expression vector and construction of libraries capable of identifying essential genes. Preliminary screening will begin in Phase I. Phase II of the project will entail improving and expanding the process, identifying all susceptible essential genes in Aspergillusfumigatus and developing screens for new antifungals based on these essential genes. Elitra's exclusive license to Incyte Pharmaceutical's PathoSeqTM database, which includes A. furnigatus sequence, will greatly expedite bioinformatic analysis of positives. The method proposed for identifying essential genes can be automated and is well suited for Aspergillusfumigatus, a haploid human pathogen not amenable to classical genetic analysis.
Elitra is creating a unique relational database of both targets and drug screens for major gene/protein targets across multiple pathogens. This database will markedly enhance the ability of Elitra and its corporate partners to make informed decisions about which novel targets to pursue. Elitra has built a unique, ultra rapid Gene-to-Screen technology platform that will allow miniaturized drug screens to be rapidly developed for any validated target in its proprietary database. Screening will be undertaken with Elitra's in-house chemical library of 250,000 plus compounds.