Production of Functional Anti-Ebola Antibodies in Pichia pastoris

Oliver Purcell, Patrick Opdensteinen, William Chen, Ky Lowenhaupt, Alexander Brown, Mario Hermann, Jicong Cao, Niklas Tenhaef, Eric Kallweit, Robin Kastilan, Anthony J. Sinskey, Pablo Perez-Pinera, Johannes F. Buyel, Timothy K. Lu

Research output: Contribution to journalArticle

Abstract

The 2013-2016 Ebola outbreak highlighted the limited treatment options and lack of rapid response strategies for emerging pathogen outbreaks. Here, we propose an efficient development cycle using glycoengineered Pichia pastoris to produce monoclonal antibody cocktails against pathogens. To enable rapid genetic engineering of P. pastoris, we introduced a genomic landing pad for reliable recombinase-mediated DNA integration. We then created strains expressing each of the three monoclonal antibodies that comprise the ZMapp cocktail, and demonstrated that the secreted antibodies bind to the Ebola virus glycoprotein by immunofluorescence assay. We anticipate that this approach could accelerate the production of therapeutics against future pathogen outbreaks.

Original languageEnglish (US)
Pages (from-to)2183-2190
Number of pages8
JournalACS synthetic biology
Volume6
Issue number12
DOIs
StatePublished - Dec 15 2017

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Keywords

  • Ebola
  • Pichia pastoris
  • antibodies
  • biologics

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

Cite this

Purcell, O., Opdensteinen, P., Chen, W., Lowenhaupt, K., Brown, A., Hermann, M., Cao, J., Tenhaef, N., Kallweit, E., Kastilan, R., Sinskey, A. J., Perez-Pinera, P., Buyel, J. F., & Lu, T. K. (2017). Production of Functional Anti-Ebola Antibodies in Pichia pastoris. ACS synthetic biology, 6(12), 2183-2190. https://doi.org/10.1021/acssynbio.7b00234