Michellamine B is a potential anti-HIV agent in advanced preclinical development within the NCI. Further clinical development and trials are limited by an acute shortage of supply and no long-term source for commercial supply has been identified. The long-term objective of this proposal is to produce Michellamine B in bulk using a plant cell-culture process. Innovative cell culture growth establishment and maintenance, product formation and monitoring, and germplasm screening strategies will be developed in a comprehensive and integrated manner.
The specific aim of Phase I research is to establish the feasibility using plant cell cultures for Michellamine B production by accomplishing five enabling objectives: 1) Develop network for germplasm collection. 2) Establish callus cultures and develop maintenance techniques. 3) Refine analytical methods for the detection and quantitation of Michellamine B. 4) Establish cell suspensions from callus cell lines and develop preliminary conditions favoring growth and product formation. 5) Screen cell lines from an available germplasm pool and identify a few elite lines capable of producing Michellamine B. Technologically innovative components include i) the use of plant cell cultures for production of pharmaceuticals, ii) the use of comprehensive optimization of variables for establishment and enhancement of callus and cell suspension growth, and iii) the use of novel rapid-screening methods for identifying productive cell lines. The proposed research will help to form the basis for a scalable and commercially successful route to Michellamine B production that will be superior to other approaches.
