Recurring genomic structural variation leads to clonal instability and loss of productivity

Biotechnology and Bioengineering
Arpan A BandyopadhyayWei-Shou Hu

Abstract

Chinese hamster ovary cells, commonly used in the production of therapeutic proteins, are aneuploid. Their chromosomes bear structural abnormality and undergo changes in structure and number during cell proliferation. Some production cell lines are unstable and lose their productivity over time in the manufacturing process and during the product's life cycle. To better understand the link between genomic structural changes and productivity stability, an immunoglobulin G producing cell line was successively single-cell cloned to obtain subclones that retained or lost productivity, and their genomic features were compared. Although each subclone started with a single karyotype, the progeny quickly diversified to a population with a distribution of chromosome numbers that is not distinctive from the parent and among subclones. The comparative genomic hybridization (CGH) analysis showed that the extent of copy variation of gene coding regions among different subclones stayed at levels of a few percent. Genome regions that were prone to loss of copies, including one with a product transgene integration site, were identified in CGH. The loss of the transgene copy was accompanied by loss of transgene transcript level. Sequence analysi...Continue Reading

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Citations

Feb 9, 2020·Biotechnology Progress·Sofie A O'BrienWei-Shou Hu
Feb 19, 2021·Molecular Cytogenetics·Victoria I TurilovaTatiana K Yakovleva
Feb 2, 2021·Biotechnology and Bioengineering·Zion LeeWei-Shou Hu
Apr 26, 2021·Biotechnology Progress·Erik LangsdorfAnurag Khetan
Jan 5, 2021·Current Opinion in Chemical Engineering·Sofie A O'Brien, Wei-Shou Hu
Dec 12, 2021·Nucleic Acids Research·Raffaele AltamuraYaakov Benenson
Dec 26, 2021·Biotechnology and Bioengineering·Philipp N SpahnNathan E Lewis
Dec 23, 2021·Biotechnology and Bioengineering·Anna StadermannIngo H Gorr

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