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

Ritter, Anett and Rauschert, Tatjana and Oertli, Mevion and Piehlmaier, Daniel and Mantas, Panagiotis and Kuntzelmann, Genevieve and Lageyre, Nadine and Brannetti, Barbara and Voedisch, Bernd and Geisse, Sabine and Jostock, Thomas and Laux, Holger (2016) Disruption of the gene C12orf35 leads to increased productivities in recombinant CHO cell lines. Biotechnology and Bioengineering.

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. 2015). Here, we performed knock-down and knock-out experiments of genes located within this telomeric region of chromosome 8 to identify the gene causing the observed phenotypes of CHO-C8DEL cell lines. We present evidence that loss or reduced expression of the gene C12orf35 is responsible for 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 during the stable expression of antibodies.

Item Type: Article
Date Deposited: 15 Jun 2016 23:45
Last Modified: 15 Jun 2016 23:45
URI: https://oak.novartis.com/id/eprint/28218

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