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Mapping the molecular basis for growth related phenotypes in industrial producer CHO cell lines using differential proteomic analysis

Authors
  • Bryan, Laura1
  • Henry, Michael1
  • Kelly, Ronan M.2
  • Frye, Christopher C.2
  • Osborne, Matthew D.3
  • Clynes, Martin1
  • Meleady, Paula1
  • 1 Dublin City University, Glasnevin, Dublin 9, Ireland , Dublin 9 (Ireland)
  • 2 Eli Lilly and Company, LTC-North, 1200 Kentucky Avenue, Indianapolis, IN, 46225, USA , Indianapolis (United States)
  • 3 Eli Lilly, Kinsale Limite, Cork, Ireland , Cork (Ireland)
Type
Published Article
Journal
BMC Biotechnology
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Jul 23, 2021
Volume
21
Issue
1
Identifiers
DOI: 10.1186/s12896-021-00704-8
Source
Springer Nature
Keywords
Disciplines
  • Research
License
Green

Abstract

BackgroundThe ability to achieve high peak viable cell density earlier in CHO cell culture and maintain an extended cell viability throughout the production process is highly desirable to increase recombinant protein yields, reduce host cell impurities for downstream processing and reduce the cost of goods. In this study we implemented label-free LC-MS/MS proteomic profiling of IgG4 producing CHO cell lines throughout the duration of the cell culture to identify differentially expressed (DE) proteins and intracellular pathways associated with the high peak viable cell density (VCD) and extended culture VCD phenotypes.ResultsWe identified key pathways in DNA replication, mitotic cell cycle and evasion of p53 mediated apoptosis in high peak VCD clonally derived cell lines (CDCLs). ER to Golgi vesicle mediated transport was found to be highly expressed in extended culture VCD CDCLs while networks involving endocytosis and oxidative stress response were significantly downregulated.ConclusionThis investigation highlights key pathways for targeted engineering to generate desirable CHO cell phenotypes for biotherapeutic production.

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