Challenging the workhorse: Comparative analysis of eukaryotic micro-organisms for expressing monoclonal antibodies |
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Authors: | Hanxiao Jiang Andrew A Horwitz Chapman Wright Anna Tai Elizabeth A Znameroski Yoseph Tsegaye Hailley Warbington Benjamin S Bower Christina Alves Carl Co Kanvasri Jonnalagadda Darren Platt Jessica M Walter Venkatesh Natarajan Jeffrey A Ubersax Joel R Cherry J Christopher Love |
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Institution: | 1. Research and Development, Amyris Inc., Emeryville, California;2. Research and Development, Amyris Inc., Emeryville, California
Jiang and Horwitz contributed equally to this work.;3. Engineering & Technology, Biogen, Cambridge, Massachusetts |
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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. |
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Keywords: | alternate expression systems antibody genome engineering recombinant protein expression yeast expression systems |
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