Background
The bioproduction of therapeutic proteins such as monoclonal antibodies (mAb) continues to be a fast growing sector of advanced manufacturing. The ever increasing repertoire of therapeutic proteins coupled with the emergence of biosimilars led to increasing global demand for higher, faster, more cost-effective manufacturing process. Central to any good production platform is the capacity of the production cell line. A suitable production cell line exhibit physiological traits such as high specific productivity (qp), rapid doubling time, high peak cell density and efficient metabolism. The emergence of a suitable production cell with all the aforementioned traits is an extremely rare event, as it requires all facets of cellular transcription, translation, secretion and metabolic efficiency are individually optimized and collectively synchronized into a system capable of high level protein expression. One of the major cellular bottlenecks thought to limit protein production in mammalian cells lies in the cellular translation and secretion capacity. The over-expression of complex recombinant proteins such as mAbs driven by strong viral promoters exert considerable burden in the Endoplasmic Reticulum (ER) and Golgi apparatus. The increase in ER stress triggers the Unfolded Protein Response (UPR) which can result in cell apoptosis and possibly eliminating cells with high uptake of the Gene of Interest (GOI). We adopted host cell engineering approach using XBP1 spice ratio to expand cellular translation and secretion capacity to increase qp and improve the probability of isolating suitable high producers.