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Peptonics: a new family of cell-protecting surfactants for the recombinant expression of therapeutic proteins in mammalian cell cultures
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  • Ka Zhang,
  • Eduardo Barbieri,
  • Jacob LeBarre,
  • Shahid Rameez,
  • Sigma Mostafa,
  • Stefano Menegatti
Ka Zhang
NC State University
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Eduardo Barbieri
NC State University
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Jacob LeBarre
NC State University
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Shahid Rameez
Merck & Co Inc
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Sigma Mostafa
KBI Biopharma
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Stefano Menegatti
NC State University

Corresponding Author:[email protected]

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Polymer surfactants are key components of cell culture media as they prevent mechanical damage during fermentation in stirred bioreactors. Among cell-protecting surfactants, Pluronics are widely utilized in biomanufacturing to ensure high cell viability and productivity. Mono-dispersity of monomer sequence and length is critical for the effectiveness of Pluronics - since minor deviations can damage the cells - but is challenging to achieve due to the stochastic nature of polymerization. Responding to this challenge, this study introduces Peptonics, a novel family of peptide and peptoid surfactants whose monomer composition and sequence are de-signed to achieve high cell viability and productivity at a fraction of chain length and cost of Pluronics. A designed ensemble of Peptonics was initially characterized via light scattering and tensiometry to select sequences whose phase behavior and tensioactivity align with those of Pluronics. Selected sequences were evaluated as cell-protecting surfactants using Chinese hamster ovary (CHO) cells expressing therapeutic monoclonal antibodies (mAb). Peptonics IH-T1010, ih-T1010, and ih-T1020 afforded high cell density (up to 3·107 cells·mL-1) and viability (up to 95% within 10 days of culture), while reducing the accumulation of ammonia (a toxic metabolite) by ~10% compared to Pluronic F-68. Improved cell viability afforded high mAb titer (up to 5.5 mg·mL-1) and extended the production window beyond 14 days; notably, Peptonic IH-T1020 decreased mAb fragmentation and aggregation ~5%, and lowered the titer of host cell proteins by 16% compared to Pluronic F-68. These features can improve significantly purification of mAbs, thus increasing their availability at lower cost to patients.
02 Jun 2023Submitted to Biotechnology Journal
02 Jun 2023Submission Checks Completed
02 Jun 2023Assigned to Editor
05 Jun 2023Reviewer(s) Assigned
08 Jul 2023Review(s) Completed, Editorial Evaluation Pending
10 Jul 2023Editorial Decision: Revise Major
06 Aug 20231st Revision Received
09 Aug 2023Submission Checks Completed
09 Aug 2023Assigned to Editor
09 Aug 2023Reviewer(s) Assigned
04 Oct 2023Review(s) Completed, Editorial Evaluation Pending
05 Oct 2023Editorial Decision: Accept