A Novel System for Producing Pharmaceutical Proteins

DESCRIPTION (provided by applicant): Rxoa Biosciences, in collaboration with Arizona State University, is developing a novel maize-based production system for manufacturing pharmaceutical proteins. Transgenic maize seeds are employed as bioreactors to produce desired proteins to high intracellular concentrations. These proteins are then purified from the seed in a process analogous to purification from more traditional biomanufacturing systems. The system is based on existing technology that uses a stable transgenic expression vector carrying fragments of a plant geminivirus (a Gemini vector). In the presence of a geminivurus replication associated protein (Rep), the Gemini vector DMA is precisely excised from the plant genome and replicated episomally. Episomal vector amplification leads to very high intracellular concentrations of transgene mRNA and the encoded transgenic protein product. In this research, the technology will be transferred from the dicot systems used previously to create a hybrid maize system that permits controlled amplification of the transgene following seed fertilization. Whereas earlier incarnations of the technology were impractical at large scale, this system will provide a commercially applicable process. The specific aims of the Phase I proposal are to: 1. Design and assemble the molecular reagents for a monocot seed-based Gemini vector system. 2. Validate the molecular reagents in a maize cell system. 3. Assemble the necessary molecular and biochemical components for producing and analyzing transgenic maize plants during Phase II. Protein based pharmaceuticals are an increasingly important tool for addressing major heath issues such as cancer, viral infections, autoimmune diseases and heart disease. Current protein drug manufacturing processes may not meet future production demands. Rxoa Biosciences is developing a novel plant-based production system to increase protein production capacity and reduce overall protein drug costs.