Growth Rate Changes in CHO Host Cells Are Associated with Karyotypic Heterogeneity

Growth Rate Changes in CHO Host Cells Are Associated with Karyotypic Heterogeneity IntroductionChinese hamster ovary (CHO) cells have been widely used for biopharmaceutical manufacturing. While many efforts have been made to achieve improved productivity and product quality of recombinant proteins produced in CHO cells, a number of studies have described cell line instability, such as a decrease in productivity, reduced culture longevity, or varied host cell protein expression during extended cell cultures. Cell line instability results in variability in the biomanufacturing process that can affect cost or regulatory compliance, yet the causes and mechanisms of cell line instability remain elusive. Given the hypothesis that cell line instability is associated with chromosomal rearrangements, we previously developed and applied a karyotype‐based framework to quantify chromosomal rearrangements in secreted alkaline phosphatase (SEAP)‐producing CHO cells that exhibited production instability. Karyotyping and fluorescence in situ hybridization analysis demonstrated that the SEAP production instability was associated with a particular chromosomal rearrangement, suggesting a mutation‐and‐selection mechanism. It has also recently been shown that a substantial number of genomic rearrangements occur after transgene integration.Cell line instability in CHO host cells has not been well understood compared to that in production cell lines. As production cell lines are generated through transfection of host cells with transgenes followed by isolation of http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biotechnology Journal Wiley

Growth Rate Changes in CHO Host Cells Are Associated with Karyotypic Heterogeneity

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Publisher
Wiley
Copyright
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
ISSN
1860-6768
eISSN
1860-7314
D.O.I.
10.1002/biot.201700230
Publisher site
See Article on Publisher Site

Abstract

IntroductionChinese hamster ovary (CHO) cells have been widely used for biopharmaceutical manufacturing. While many efforts have been made to achieve improved productivity and product quality of recombinant proteins produced in CHO cells, a number of studies have described cell line instability, such as a decrease in productivity, reduced culture longevity, or varied host cell protein expression during extended cell cultures. Cell line instability results in variability in the biomanufacturing process that can affect cost or regulatory compliance, yet the causes and mechanisms of cell line instability remain elusive. Given the hypothesis that cell line instability is associated with chromosomal rearrangements, we previously developed and applied a karyotype‐based framework to quantify chromosomal rearrangements in secreted alkaline phosphatase (SEAP)‐producing CHO cells that exhibited production instability. Karyotyping and fluorescence in situ hybridization analysis demonstrated that the SEAP production instability was associated with a particular chromosomal rearrangement, suggesting a mutation‐and‐selection mechanism. It has also recently been shown that a substantial number of genomic rearrangements occur after transgene integration.Cell line instability in CHO host cells has not been well understood compared to that in production cell lines. As production cell lines are generated through transfection of host cells with transgenes followed by isolation of

Journal

Biotechnology JournalWiley

Published: Jan 1, 2018

Keywords: ; ; ; ; ;

References

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