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Recombinant antibody-producing stable CHOK1 pool stability study
  • +15
  • Bailin Tu,
  • Zhihong Lin,
  • Jeff Moore,
  • Archana Sekaran,
  • Miranda Wesley,
  • De Yu Mao,
  • Mark Gibson,
  • Wan-Ching Lai,
  • John Boggs,
  • Thomas Slowik,
  • Yeni Natalia Perez-Gelvez,
  • Ryan Bonn,
  • Tracey Rae,
  • Jeremy Minshull,
  • Ferenc Boldog,
  • Varsha Sitaraman,
  • Scott Muerhoff,
  • Philip Hemken
Bailin Tu
Abbott Laboratories

Corresponding Author:[email protected]

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Zhihong Lin
Abbott Laboratories
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Jeff Moore
Abbott Laboratories
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Archana Sekaran
Abbott Laboratories
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Miranda Wesley
Abbott Laboratories
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De Yu Mao
Abbott Laboratories
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Mark Gibson
Abbott Laboratories
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Wan-Ching Lai
Abbott Laboratories
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John Boggs
Abbott Laboratories
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Thomas Slowik
Abbott Laboratories
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Yeni Natalia Perez-Gelvez
Abbott Laboratories
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Ryan Bonn
Abbott Laboratories
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Tracey Rae
Abbott Laboratories
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Jeremy Minshull
ATUM
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Ferenc Boldog
ATUM
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Varsha Sitaraman
ATUM
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Scott Muerhoff
Abbott Laboratories
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Philip Hemken
Abbott Laboratories
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Abstract

Mammalian cell line stability is an important consideration when establishing a biologics manufacturing process in the biopharmaceutical and in vitro diagnostics (IVD) industries. Traditional CHO cell line development methods use a random integration approach that requires transfection, selection, optional amplification, screenings, and single-cell cloning to select clones with acceptable productivity, product quality, and genetic stability. Site-specific integration reduces these disadvantages, and new technologies have been developed to mitigate risks associated with genetic instability. In this study, we applied the Leap-In® transposase-mediated expression system from ATUM to generate stable CHOK1 pools for the production of four recombinant antibody reagents for IVD immunoassays. CHO cell line stability is defined by consistent antibody production over time. Three of the CHOK1 pools maintained productivity suitable for manufacturing, with high antibody yields. The productivity of the remaining CHOK1 pool decreased over time; however, derivative clones showed acceptable stability. L-glutamine had variable effects on CHOK1 cell line or stable pool stability and significantly affected antibody product titer. Compared with traditional random integration methods, the ATUM Leap-In system can reduce the time needed to develop new immunoassays by using semi-site specific integration to generate high yield stable pools that meet manufacturing stability requirements.