Selection of CHO host and recombinant cell pools by inhibition of the proteasome results in enhanced product yields and cell specific productivity

Chinese hamster ovary (CHO) cells are the leading mammalian cell expression platform for biotherapeutic recombinant molecules yet some proteins remain difficult to express (DTE) in this, and other, systems. In lines expressing DTE proteins, cellular processes restore proteostasis can be triggered when folding modification capabilities exceeded, including unfolded protein response ER-associated degradation (ERAD) proteasomal degradation. We therefore investigated whether proteasome activity of CHO was linked their ability produce proteins. found with diverse monoclonal antibody (mAb) productivity show different susceptibilities inhibitors activity. Subsequently, we applied selective pressure using on mAb producing determine impact growth production, apply above that a metabolic selection marker during pool construction. The presence construction two model molecules, Fc-fusion protein, resulted generation pools enhanced productivity. increased productivities, select higher cells, has potential improve clonal upstream