CHO Cell Engineering for Improved Process Performance and Product Quality

Although CHO cells have been successfully employed as a manufacturing host cell system for decades, these cell lines still suffer from naturally occurring limitations with regard to growth rates and recombinant protein production capacity. Especially with the advent of difficulty to express protein therapeutics as multispecific antibody formats as well as fusion proteins, there is an urgent demand to steadily improve industrial CHO host cell lines in order to be prepared for future bioprocessing challenges. Therefore, host cell engineering of CHO cells represents a valuable strategy to overcome the limitations in the production of biologics. There are different opportunities to counteract limitations of mammalian cell factories. Increasing cellular growth rates or suppressing cell death will result in accelerated biomass accumulation and prolonged cultivation processes. Furthermore, increasing cell viabilities toward the end of the production run facilitates cell culture harvesting and contributes to successful bioprocess development and hence reduces scale‐up issues. Enhancing cell‐specific productivity can improve final product yields, and modulating endogenous proteins involved in post‐translational modifications can lead to tailored product quality. In the following chapters, we have summarized the most relevant cell line engineering techniques currently applied for CHO cell engineering and provide an overview on the current state of the art.