Large-Scale Transient Transfection of Suspension-Adapted Chinese Hamster Ovary Cells for the Production of the Trimeric SARS-CoV-2 Spike Protein

Methods Mol Biol. 2025:2853:7-16. doi: 10.1007/978-1-0716-4104-0_2.

Abstract

The production and purification of the secreted ectodomain of SARS-CoV-2 spike protein (S protein) were performed by transiently transfecting suspension-adapted Chinese hamster ovary cells (ExpiCHO). The method involved the separate addition of plasmid DNA expressing the S protein and polyethyleneimine to a suspension culture at a density of 5 × 106 cells/mL; and the subsequent addition of dimethyl sulfoxide at 2% (v/v). The transfected ExpiCHO cells were cultivated at 31 °C with agitation by orbital shaking under 5% CO2. On day six post-transfection, the culture was centrifuged, and the supernatant was filtered to remove cells and cell debris. Finally, the secreted recombinant S protein was recovered from the supernatant by a single step of affinity chromatography to the Twin-Strep-Tag of the recombinant S protein.

Keywords: CHO cells; Orbital shaking; Polyethyleneimine; Protein purification; Recombinant protein; Transfection.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus*
  • Plasmids / genetics
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / metabolism
  • Spike Glycoprotein, Coronavirus* / genetics
  • Spike Glycoprotein, Coronavirus* / metabolism
  • Transfection* / methods

Substances

  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • Recombinant Proteins