Application of Sodium Butyrate for the Enhanced Production of hCTLA4Ig in Transgenic Rice Suspension Cell Cultures

초록

Plant cells have some advantages as a host for the production of therapeutic proteins, such as low production cost and safety from animal pathogens. Recently, many therapeutic proteins are produced using transgenic plant cell cultures. Transgenic rice cell cultures (Oryza sativa L.) with inducible RAmy3D promoter were used to express recombinant human cytotoxic T-lymphocyte antigen 4-immunoglobulin (hCTLA4Ig), a soluble fusion protein to be used for the treatment of rheumatoid arthritis. Commercial name of the fusion protein is Orencia, which was approved by US FDA in 2005. The RAmy3D promoter is strongly expressed under the induction condition by sugar starvation and the rice cells secreted hCTLA4Ig into the medium. Sodium butyrate (NaBu) has been used to enhance the production of foreign proteins in Chinese hamster ovary (CHO) cell cultures due to its harmlessness, easy manipulation and cost-effectiveness. However, it can also inhibit cell growth and induce cellular apoptosis. In this study, for the enhanced production of hCTLA4Ig, effects of NaBu on cell growth and protein production were investigated. Feeding time and methods were optimized in addition to the supplementation of additional energy sources. In conclusion, the production of hCTLA4Ig could be significantly enhanced by the optimization of NaBu feeding strategy with additional energy sources in transgenic rice cell cultures.