ISOLATION OF TARGETS FOR ANTIFUNGAL DRUGS IN C. ALBICANS

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Candida albicans is an important human pathogen that is the leading cause of invasive fungal disease in surgical patients, infants, diabetics and immunocomprimised individuals. Despite treatment with cytostatic drugs, the rate of mortality from systemic Candida infections approaches 30%. A major impediment to the development of new drugs is the difficulty of identifying suitable targets for drug design. The biology of Candida precludes the use of a classical genetic approach to identify target genes. In this phase application, we propose to apply novel approaches to inhibit gene function in Candida. First, we will apply an approach that we have employed successfully in mammalian cells: to inhibit the function of genes by the expression of antisense RNA. We also propose to assess the utility of a newly emerging method for creating loss-of-function phenotypes: the expression of double-stranded RNA. The goal of this phase I application is to demonstrate the feasibility of performing genetic screens in Candida by ablating gene function with antisense RNA or with double-stranded RNA. PROPOSED COMMERCIAL APPLICATION: The ability to identify suitable targets for drug design in Candida albicans will yield two potential avenues for commercialization. First, the targets can be deployed as drug-discovery candidates with the help of corporate partners. Second, the technical approaches described herein may be applied in collaboration with one or more corporate partners.