Engineered and Natural Promoters and Chromatin‐Modifying Elements for Recombinant Protein Expression in CHO Cells

Engineered and Natural Promoters and Chromatin‐Modifying Elements for Recombinant Protein... IntroductionChinese hamster ovary (CHO) cell lines are the most commonly used mammalian cells both for research and for industrial recombinant protein therapeutics production. In the last decades, CHO cell productivity has reached gram‐per liter mark, which is a 100‐fold increase since the first product approval of tissue plasminogen activator (tPA), in 1986.Due to their metabolic plasticity, immense adaptability, and ease of maintenance CHO cells remain widely exploited for various purposes. Discovery of auxotrophic mutants deficient in the dihydrofolate reductase (DHFR) enzyme aided establishment of the expression system, allowing easy clonal selection and gene amplification. The resulting double deletion cell line CHO‐DG44 became a workhorse for many recombinant products. CHO cells are capable of correct protein folding and post‐translational modifications, compatible with the human immune system, increasing their value for therapeutic recombinant product production.Despite recent advances, the generation of high‐producing cell lines is still a very demanding, arduous, and multi‐step process which involves vector design, transformation, and an elaborate selection for high producing clones. It is estimated that the complete process required for the establishment of designated stable producing cell line can require 4 to 12 months.Many technologies for optimization of heterologous protein production have been generated over the last http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biotechnology Journal Wiley

Engineered and Natural Promoters and Chromatin‐Modifying Elements for Recombinant Protein Expression in CHO Cells

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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.201700232
Publisher site
See Article on Publisher Site

Abstract

IntroductionChinese hamster ovary (CHO) cell lines are the most commonly used mammalian cells both for research and for industrial recombinant protein therapeutics production. In the last decades, CHO cell productivity has reached gram‐per liter mark, which is a 100‐fold increase since the first product approval of tissue plasminogen activator (tPA), in 1986.Due to their metabolic plasticity, immense adaptability, and ease of maintenance CHO cells remain widely exploited for various purposes. Discovery of auxotrophic mutants deficient in the dihydrofolate reductase (DHFR) enzyme aided establishment of the expression system, allowing easy clonal selection and gene amplification. The resulting double deletion cell line CHO‐DG44 became a workhorse for many recombinant products. CHO cells are capable of correct protein folding and post‐translational modifications, compatible with the human immune system, increasing their value for therapeutic recombinant product production.Despite recent advances, the generation of high‐producing cell lines is still a very demanding, arduous, and multi‐step process which involves vector design, transformation, and an elaborate selection for high producing clones. It is estimated that the complete process required for the establishment of designated stable producing cell line can require 4 to 12 months.Many technologies for optimization of heterologous protein production have been generated over the last

Journal

Biotechnology JournalWiley

Published: Jan 1, 2018

Keywords: ; ; ; ;

References

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