Changes in Chromosome Counts and Patterns in CHO Cell Lines upon Generation of Recombinant Cell Lines and Subcloning

Changes in Chromosome Counts and Patterns in CHO Cell Lines upon Generation of Recombinant Cell... IntroductionMammalian‐based expression systems make up more than 60% of the biopharmaceutical market, with sales exceeding 140 billion dollars in 2013. Among these systems, Chinese hamster ovary (CHO) cells account for the majority of approved products and are state of the art for the production of recombinant protein therapeutics. Large and complex‐structured biologics require human‐like post‐translational modifications in order to be non‐immunogenic and functional, a feature that is adequately fulfilled by CHO cells. On the downside, CHO cells, like all rapidly growing and immortalized cell lines, are genomically unstable, intraclonally heterogeneous, and frequently undergo genotypic variations. These lead to phenotypic instability and hence problems with respect to process reproducibility or production instability. As a consequence of such genotypic drifts, CHO cells are quasi‐diploid with a chromosome number that diverges from that of the primary Chinese hamster and with different karyotypes and modal chromosome numbers for each cell line analyzed.To overcome the heterogenic nature of CHO cells, a lot of effort is put into clone and cell line development in order to obtain a clonal cell line with advantageous growth, productivity, and stable properties. The requirement for clonality is based on the assumption that subclones are phenotypically and genetically homogenous and http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biotechnology Journal Wiley

Changes in Chromosome Counts and Patterns in CHO Cell Lines upon Generation of Recombinant Cell Lines and Subcloning

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
ISSN
1860-6768
eISSN
1860-7314
D.O.I.
10.1002/biot.201700495
Publisher site
See Article on Publisher Site

Abstract

IntroductionMammalian‐based expression systems make up more than 60% of the biopharmaceutical market, with sales exceeding 140 billion dollars in 2013. Among these systems, Chinese hamster ovary (CHO) cells account for the majority of approved products and are state of the art for the production of recombinant protein therapeutics. Large and complex‐structured biologics require human‐like post‐translational modifications in order to be non‐immunogenic and functional, a feature that is adequately fulfilled by CHO cells. On the downside, CHO cells, like all rapidly growing and immortalized cell lines, are genomically unstable, intraclonally heterogeneous, and frequently undergo genotypic variations. These lead to phenotypic instability and hence problems with respect to process reproducibility or production instability. As a consequence of such genotypic drifts, CHO cells are quasi‐diploid with a chromosome number that diverges from that of the primary Chinese hamster and with different karyotypes and modal chromosome numbers for each cell line analyzed.To overcome the heterogenic nature of CHO cells, a lot of effort is put into clone and cell line development in order to obtain a clonal cell line with advantageous growth, productivity, and stable properties. The requirement for clonality is based on the assumption that subclones are phenotypically and genetically homogenous and

Journal

Biotechnology JournalWiley

Published: Jan 1, 2018

Keywords: ; ; ; ;

References

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