The overall goal of the proposed R&D program is to develop improved methodologies and manufacturing processes for the isolation of marine natural products with anticancer or anti-HIV activity. The therapeutic potential of marine natural products has rapidly advanced in recent years. One such potential therapeutic is bryostatin I which is derived from the marine bryozoan Bugula neritana. While harvesting the bryozoan with consistent sources of the active agent will become a significant portion of the supply problem, large-scale manufacturing of the natural product agent will also pose significant challenges to processing logistics and manufacturing costs. In the proposed effort, our specific aim is to investigate the application of supercritical fluid extraction and chromatography for the isolation and purification of bryostatin I since these techniques have shown promise for the large scale manufacturing of certain anti cancer agents such as taxol from terrestrial biomass sources. In this effort, we plan to collaborate with CalBioMarine who will supply both naturally occurring and aquacultured quantities of B. neritina. This investigation should lead to the establishment of improved manufacturing processes for producing large quantities of marine natural product agents needed for preclinical and clinical development.