Challenging the workhorse: Comparative analysis of eukaryotic micro‐organisms for expressing monoclonal antibodies
Name
Jiang_et_al-2019-Biotechnology_and_Bioengineering.pdf
Description
Published version
Size
884.03 KB
Format
Adobe PDF
Checksum (MD5)
2daf7458f3689189de9e40138b00a3f1
Author(s)
Jiang, Hanxiao
Horwitz, Andrew A
Wright, Chapman
Tai, Anna
Znameroski, Elizabeth A
Tsegaye, Yoseph
Warbington, Hailley
Bower, Benjamin S
Alves, Christina
Co, Carl
Date Issued
2019
Journal
Biotechnology and Bioengineering
Publisher
Wiley
Version
Final published version
Abstract
© 2019 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc. 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.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1002/BIT.26951
