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Recombinant CHO (Chinese hamster ovary) cell lines producing therapeutic proteins often lose their production capability during long-term cultivation. To ensure that CHO production cell lines can be up-scaled to high-volume bioreactors, labor intensive stability studies of several months have to be performed to deselect clones that are losing productivity over time. The ability to predict whether clones will produce recombinant proteins at constant high levels, for example, through determination of biomarkers such as expression of specific genes, plasmid integration sites, or epigenetic patterns, or even to improve CHO host cell lines to increase the probability of the generation of stable clones would be highly beneficial. Previously, we reported that the lack of a telomeric region of chromosome 8 correlates with increased productivities and higher production stabilities of monoclonal antibody expressing CHO cell lines (Ritter A, Voedisch B, Wienberg J, Wilms B, Geisse S, Jostock T, Laux H. 2016a. Biotechnol Bioeng 113(5):1084-1093). Herein, we describe that the knock-out of the gene Fam60A, which is one of the genes located within the telomeric region of chromosome 8, in CHO-K1a cells leads to the isolation of significantly more clones with higher protein production stabilities of monoclonal antibodies during long-term cultivation. |
