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Cited by 322Viral Infectious Diseases and Gene Expression in InsectsProtein purification and stabilityMonoclonal and Polyclonal Antibodies Research

Advances in Mammalian cell line development technologies for recombinant protein production

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Lai, Tingfeng, Yang, Yuansheng, Ng, Say·2013·Pharmaceuticals
DOI 10.3390/ph6050579PMC PMC3817724
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Abstract

From 2006 to 2011, an average of 15 novel recombinant protein therapeutics have been approved by US Food and Drug Administration (FDA) annually. In addition, the expiration of blockbuster biologics has also spurred the emergence of biosimilars. The increasing numbers of innovator biologic products and biosimilars have thus fuelled the demand of production cell lines with high productivity. Currently, mammalian cell line development technologies used by most biopharmaceutical companies are based on either the methotrexate (MTX) amplification technology or the glutamine synthetase (GS) system. With both systems, the cell clones obtained are highly heterogeneous, as a result of random genome integration by the gene of interest and the gene amplification process. Consequently, large numbers of cell clones have to be screened to identify rare stable high producer cell clones. As such, the cell line development process typically requires 6 to 12 months and is a time, capital and labour intensive process. This article reviews established advances in protein expression and clone screening which are the core technologies in mammalian cell line development. Advancements in these component technologies are vital to improve the speed and efficiency of generating robust and highly productive cell line for large scale production of protein therapeutics.

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  • CHO cells can achieve substantial production rate, are suitable for large-scale industrial suspension culture, and can be adapted to grow in various serum-free and chemically defined culture media.

    “These cells can achieve substantial production rate, are suitable for large-scale industrial suspension culture and can be adapted to grow in various serum-free and chemically defined culture media (Kim et al., 2012;Lai et al., 2013).”

    From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Lai et al., 2013

  • Because CHO cells produce recombinant glycoproteins with human-like glycans, the generated products are more likely to be compatible and bioactive within human hosts.

    “Since CHO cells produce recombinant glycoproteins with human-like glycans, the generated products are to more likely be compatible and bioactive within human hosts (Kim et al., 2012;Lai et al., 2013).”

    From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Lai et al., 2013

  • Different gene amplification systems developed and used in CHO cells allow high titer yields and good specific productivity.

    “Moreover, different gene amplification systems have been developed and used in CHO cells, which allow for high titer yields and good specific productivity (Durocher and Butler, 2009;Kim et al., 2012;Lai et al., 2013).”

    From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Lai et al., 2013

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Cited by

Sorted by citations

Authors
Lai, T., Yang, Y., & Ng, S.
Affiliations
Agency for Science, Technology and Research (SG)
Corresponding author
Ng, Say
ORCID
Venue
Pharmaceuticals
Publisher
MDPI AG
Published
2013-04-26
Volume
6
Issue
5
Pages
579-603
ISSN
1424-8247 (ISSN-L)
DOI
10.3390/ph6050579
PMC
PMC3817724
OpenAlex
W2123607534
Cited by
322
References
6
Citations by year
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FWCI
8.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Pharmaceuticals (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • National University of Singapore (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DR-NTU (Nanyang Technological University) (submittedVersion)
Funders
  • Agency for Science, Technology and Research
  • Biomedical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
Keywords
recombinant protein expression, therapeutic proteins, biosimilars, clone screening, gene amplification, biopharmaceutical manufacturing

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