Cell Culture Engineering

Many recombinant therapeutics are complex glycoproteins for which mammalian cells are the preferred expression systems. With the advent of biosimilars, there is a further need to increase the productivity of these cell lines and accelerate process development. We are investigating the role of the protein secretion pathway in limiting the productivity of a panel of CHO cell lines that produce monoclonal antibodies at varying productivity levels from 5 pg/cell/day to 50 pg/cell/day. The experiments are coupled with a mathematical model to guide our efforts to modulate the levels of unfolded protein response UPR pathways genes, using siRNA or chemical inhibitors. Further, we wish to understand the effect of process parameters and reactor configurations on cellular stress and productivity