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

doi:10.1021/acssynbio.7b00234

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 journal › Article › peer-review

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 language	English (US)
Pages (from-to)	2183-2190
Number of pages	8
Journal	ACS synthetic biology
Volume	6
Issue number	12
DOIs	https://doi.org/10.1021/acssynbio.7b00234
State	Published - Dec 15 2017

Keywords

Ebola
Pichia pastoris
antibodies
biologics

ASJC Scopus subject areas

Biomedical Engineering
Biochemistry, Genetics and Molecular Biology (miscellaneous)

Online availability

10.1021/acssynbio.7b00234

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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.",

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AU - Purcell, Oliver

AU - Opdensteinen, Patrick

AU - Chen, William

AU - Lowenhaupt, Ky

AU - Brown, Alexander

AU - Hermann, Mario

AU - Cao, Jicong

AU - Tenhaef, Niklas

AU - Kallweit, Eric

AU - Kastilan, Robin

AU - Sinskey, Anthony J.

AU - Perez-Pinera, Pablo

AU - Buyel, Johannes F.

AU - Lu, Timothy K.

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Y1 - 2017/12/15

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AB - 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.

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Production of Functional Anti-Ebola Antibodies in Pichia pastoris

Abstract

Keywords

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