Challenging the workhorse: Comparative analysis of eukaryotic micro‐organisms for expressing monoclonal antibodies. Issue 6 (7th March 2019)

• Record Type: Journal Article
• Authors: Jiang, Hanxiao; Horwitz, Andrew A.; Wright, Chapman; Tai, Anna; Znameroski, Elizabeth A.; Tsegaye, Yoseph; Warbington, Hailley; Bower, Benjamin S.; Alves, Christina; Co, Carl; Jonnalagadda, Kanvasri; Platt, Darren; Walter, Jessica M.; Natarajan, Venkatesh; Ubersax, Jeffrey A.; Cherry, Joel R.; Love, J. Christopher
• Is Part Of: Biotechnology and bioengineering. Volume 116:Issue 6(2019)
• Page Start: 1449
• Page End: 1462
• Publication Date: 2019-03-07
• Subjects: alternate expression systems -- antibody -- genome engineering -- recombinant protein expression -- yeast expression systems; Biotechnology -- Periodicals; Bioengineering -- Periodicals; 660.6
• DOI: 10.1002/bit.26951
• Languages: English
• ISSNs: 0006-3592

Abstract

Abstract: For commercial protein therapeutics, Chinese hamster ovary (CHO) cells have an established history of safety, proven capability to express a wide range of therapeutic proteins and high volumetric productivities. Expanding global markets for therapeutic proteins and increasing concerns for broadened access of these medicines has catalyzed consideration of alternative approaches to this platform. Reaching these objectives likely will require an order of magnitude increase in volumetric productivity and a corresponding reduction in the costs of manufacture. For CHO‐based manufacturing, achieving this combination of targeted improvements presents challenges. Based on a holistic analysis, the choice of host cells was identified as the single most influential factor for both increasing productivity and decreasing costs. Here we evaluated eight wild‐type eukaryotic micro‐organisms with prior histories of recombinant protein expression. The evaluation focused on assessing the potential of each host, and their corresponding phyla, with respect to key attributes relevant for manufacturing, namely (a) growth rates in industry‐relevant media, (b) adaptability to modern techniques for genome editing, and (c) initial characterization of product quality. These characterizations showed that multiple organisms may be suitable for production with appropriate engineering and development and highlighted that yeast in general present advantages for rapid genome engineering and development cycles. Abstract : In this work, we present a comparative study of the potential of eight different eukaryotic microorganisms (yeasts, fungi, diatom, and protozoan) as alternative hosts for the expression of recombinant biopharmaceuticals. The study assesses the suitability of these hosts in a 'head‐to‐head' manner that would allow direct comparisons of their tractability for high‐density cultivation, engineering with advanced genome editing tools (CRISPR/Cas9), and the molecular attributes of recombinant antibodies expressed in the tractable hosts.