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Multiplex secretome engineering enhances recombinant protein production and purity

Author

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  • Stefan Kol

    (The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet)

  • Daniel Ley

    (The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet)

  • Tune Wulff

    (The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet)

  • Marianne Decker

    (The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet)

  • Johnny Arnsdorf

    (The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet)

  • Sanne Schoffelen

    (The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet)

  • Anders Holmgaard Hansen

    (The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet)

  • Tanja Lyholm Jensen

    (The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet)

  • Jahir M. Gutierrez

    (The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, School of Medicine
    Department of Bioengineering, University of California, San Diego, School of Medicine)

  • Austin W. T. Chiang

    (The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, School of Medicine
    Department of Pediatrics, University of California, San Diego, School of Medicine)

  • Helen O. Masson

    (The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, School of Medicine
    Department of Bioengineering, University of California, San Diego, School of Medicine)

  • Bernhard O. Palsson

    (The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet
    The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, School of Medicine
    Department of Bioengineering, University of California, San Diego, School of Medicine
    Department of Pediatrics, University of California, San Diego, School of Medicine)

  • Bjørn G. Voldborg

    (The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet)

  • Lasse Ebdrup Pedersen

    (The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet)

  • Helene Faustrup Kildegaard

    (The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet)

  • Gyun Min Lee

    (The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Building 220, Kemitorvet
    Department of Biological Sciences, KAIST, 291 Daehak-ro, Yuseong-gu)

  • Nathan E. Lewis

    (The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, School of Medicine
    Department of Bioengineering, University of California, San Diego, School of Medicine
    Department of Pediatrics, University of California, San Diego, School of Medicine)

Abstract

Host cell proteins (HCPs) are process-related impurities generated during biotherapeutic protein production. HCPs can be problematic if they pose a significant metabolic demand, degrade product quality, or contaminate the final product. Here, we present an effort to create a “clean” Chinese hamster ovary (CHO) cell by disrupting multiple genes to eliminate HCPs. Using a model of CHO cell protein secretion, we predict that the elimination of unnecessary HCPs could have a non-negligible impact on protein production. We analyze the HCP content of 6-protein, 11-protein, and 14-protein knockout clones. These cell lines exhibit a substantial reduction in total HCP content (40%-70%). We also observe higher productivity and improved growth characteristics in specific clones. The reduced HCP content facilitates purification of a monoclonal antibody. Thus, substantial improvements can be made in protein titer and purity through large-scale HCP deletion, providing an avenue to increased quality and affordability of high-value biopharmaceuticals.

Suggested Citation

  • Stefan Kol & Daniel Ley & Tune Wulff & Marianne Decker & Johnny Arnsdorf & Sanne Schoffelen & Anders Holmgaard Hansen & Tanja Lyholm Jensen & Jahir M. Gutierrez & Austin W. T. Chiang & Helen O. Masson, 2020. "Multiplex secretome engineering enhances recombinant protein production and purity," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15866-w
    DOI: 10.1038/s41467-020-15866-w
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