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

利用靶向RNA测序技术检测产生抗体的中国仓鼠卵巢细胞系中的突变

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作者:Siyan Zhang ,Jason D Hughes ,Nicholas Murgolo ,Diane Levitan ,Janice Chen ,Zhong Liu ,Shuangping Shi

Abstract

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.

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