Disruption of the gene C12orf35 leads to increased productivities in recombinant CHO cell lines

Abstract

Recently, we reported that the loss of a telomeric region of chromosome 8 in Chinese Hamster Ovary (CHO) cells correlates with higher recombinant productivities. New cell lines lacking this region, called CHO-C8DEL, showed several advantages during cell line generation and for the production of recombinant proteins (Ritter et al., 2016, Biotechnol Bioeng). Here, we performed knock-down and knock-out experiments of genes located within this telomeric region of chromosome 8 to identify the genes causing the observed phenotypes of CHO-C8DEL cell lines. We present evidence that loss or reduced expression of the gene C12orf35 is responsible for higher productivities and shorter recovery times during selection pressure. These effects are mediated by increased levels of mRNA of the exogenes heavy chain (HC) and light chain (LC) as well as dihydrofolate reductase (DHFR) and neomycin phosphotransferase (Neo) during the stable expression of antibodies. Biotechnol. Bioeng. 2016;113: 2433-2442. © 2016 Wiley Periodicals, Inc.

Keywords: Chinese hamster ovary cells; cell line engineering; chromosomal deletion; mRNA; productivity; recombinant gene expression.