(681c) A Novel Plant Cell Based Production Platform for Secreted Protein Therapeutics

Plant cell cultures combine the merit of whole-plant system and those of microbial and animal cell culture, and have been recognized as one of the most promising production platform for therapeutic proteins. Among the various in vitro culture approaches, the suspension cells has been preferred and focused by the biochemical engineer because they are the most amenable to GMP procedures and they can be cultivated relatively easily in large-scale bioreactor. We develop a proprietary technology that allows us to produce secreted therapeutic proteins from the suspension cultured plant cells with protein yields up to 1500 fold increase. Our approach involves the expression of a heterologous protein as a fusion with a small peptide consisting of 2-20 tandem repeats of Ser-Pro motif. This peptide directs extensive Hydroxyproline-O-glycosylation upon expression in plant cells and significantly enhances the protein secretion. Furthermore, the fused Ser-Pro glycomodule improved the clinic effectiveness of the small protein therapeutics such as human growth hormone (hGH) and interferon (IFN), showing an increased in vivo serum half-life of up to 13 fold. We are currently applying this technology to hairy roots and microalgae culture system.