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

Loading next page...
 
/lp/wiley/growth-rate-changes-in-cho-host-cells-are-associated-with-karyotypic-0EtfL5WM53
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.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

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

Monthly Plan

  • Read unlimited articles
  • Personalized recommendations
  • No expiration
  • Print 20 pages per month
  • 20% off on PDF purchases
  • Organize your research
  • Get updates on your journals and topic searches

$49/month

Start Free Trial

14-day Free Trial

Best Deal — 39% off

Annual Plan

  • All the features of the Professional Plan, but for 39% off!
  • Billed annually
  • No expiration
  • For the normal price of 10 articles elsewhere, you get one full year of unlimited access to articles.

$588

$360/year

billed annually
Start Free Trial

14-day Free Trial