Multiplex secretome engineering enhances recombinant protein production and purity

Stefan Kol, Daniel Ley, Tune Wulff, Marianne Decker, Johnny Arnsdorf, Sanne Schoffelen, Anders Holmgaard Hansen, Tanja Lyholm Jensen, Jahir M. Gutierrez, Austin W.T. Chiang, Helen O. Masson, Bernhard O. Palsson, Bjørn G. Voldborg, Lasse Ebdrup Pedersen, Helene Faustrup Kildegaard, Gyun Min Lee, Nathan E. Lewis

Rannsóknarafurð: Framlag til fræðitímaritsGreinritrýni

14 Tilvitnanir (Scopus)


Host cell proteins (HCPs) are process-related impurities generated during biotherapeutic protein production. HCPs can be problematic if they pose a significant metabolic demand, degrade product quality, or contaminate the final product. Here, we present an effort to create a “clean” Chinese hamster ovary (CHO) cell by disrupting multiple genes to eliminate HCPs. Using a model of CHO cell protein secretion, we predict that the elimination of unnecessary HCPs could have a non-negligible impact on protein production. We analyze the HCP content of 6-protein, 11-protein, and 14-protein knockout clones. These cell lines exhibit a substantial reduction in total HCP content (40%-70%). We also observe higher productivity and improved growth characteristics in specific clones. The reduced HCP content facilitates purification of a monoclonal antibody. Thus, substantial improvements can be made in protein titer and purity through large-scale HCP deletion, providing an avenue to increased quality and affordability of high-value biopharmaceuticals.

Upprunalegt tungumálEnska
Númer greinar1908
FræðitímaritNature Communications
Númer tölublaðs1
ÚtgáfustaðaÚtgefið - 1 des. 2020


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