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BioMed Research International
Volume 2016 (2016), Article ID 8356435, 8 pages
Research Article

Mutation Detection in an Antibody-Producing Chinese Hamster Ovary Cell Line by Targeted RNA Sequencing

1Biologics & Vaccines, Merck Research Laboratories, Kenilworth, NJ 07033, USA
2Biology & Genetics Informatics, Merck Research Labs IT, Merck & Co, Boston, MA 02115, USA
3Discovery Pharmacogenomics, Merck Research Laboratories, Kenilworth, NJ 07033, USA

Received 18 November 2015; Revised 4 February 2016; Accepted 21 February 2016

Academic Editor: Jorge F. B. Pereira

Copyright © 2016 Siyan Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Chinese hamster ovary (CHO) cells have been used widely in the pharmaceutical industry for production of biological therapeutics including monoclonal antibodies (mAb). The integrity of the gene of interest and the accuracy of the relay of genetic information impact product quality and patient safety. Here we employed next-generation sequencing, particularly RNA-seq, and developed a method to systematically analyze the mutation rate of the mRNA of CHO cell lines producing a mAb. The effect of an extended culturing period to mimic the scale of cell expansion in a manufacturing process and varying selection pressure in the cell culture were also closely examined.