PRODUCTION OF SPONGE NATURAL PRODUCTS VIA CELL CULTURE

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The long-term objective of this project is to develop sponge cell culture methods that will satisfy and stimulate demand for marine sponge compounds for drug discovery and development: 1. Metabolite expression systems to provide small samples (<1 mg) for discovery research. 2. Optimization protocols for the development of high-yield, compound- specific production systems to support development research. 3. Controlled manufacturing systems to supply chemically-complex molecules for late development and marketing. Together these technologies will enable a series of value-added steps for each sponge-derived drug on a cost-effective and timely basis. At present, development of sponge natural products is dependent on ocean collections that are often difficult or impossible. The Developmental Therapeutics Program of the NCI plans to test thousands of sponge-derived metabolites over the next few years and has already reported sponge metabolites with antiAIDS activities. Pharmaceutical companies are also actively evaluating sponge metabolites. This project will develop technologies to support this work and ensure that adequate clinical supplies are available as needed. The proposed Phase I study will evaluate the feasibility of applying, with minor modifications, extant technologies for culture and cryopreservation of mammalian and sponge cells.