Utilization of Alternative Carbon Sources for hCTLA4Ig Production in Transgenic Rice Cell Cultures

초록

Plant cells have received considerably interest for the production of biopharmaceuticals as they were inexpensive and do not provide human pathogens. One bottleneck in plant cell cultures for commercial purposes has been low productivity. In order to overcome the constraint of low production level, Ramy3D promoter has been used for the production of the recombinant therapeutic protein in this rice cell cultures. In this study, improved production of hCTLA4Ig in transgenic rice cell line was investigated in flask cultures by supplementing alternative carbon sources. Fumarate, which is a tricarboxylic acid (TCA) cycle intermediate, was used as an alternative energy source to increase cell viability as well as the productivity of target protein. Different concentrations of fumarate (10, 20, 40 mM) was added to the sugar-depleted medium in the production phase. Cell culture conditions were also investigated to promote the productivity of targeted protein. When 5 g fresh cells in 50 mL working volume was cultivated with fumarate, the production of hCTLA4Ig was 1.3-fold higher than that of control. At 40 mM of fumarate with controlled culture condition, hCTLA4Ig production was found to be the best.