Versatile and on-demand biologics co-production in yeast

Jicong Cao, Pablo Perez-Pinera, Ky Lowenhaupt, Ming-Ru Wu, Oliver Purcell, Cesar de la Fuente-Nunez and Timothy K. Lu ()
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Jicong Cao: Massachusetts Institute of Technology
Pablo Perez-Pinera: Massachusetts Institute of Technology
Ky Lowenhaupt: Massachusetts Institute of Technology
Ming-Ru Wu: Massachusetts Institute of Technology
Oliver Purcell: Massachusetts Institute of Technology
Cesar de la Fuente-Nunez: Massachusetts Institute of Technology
Timothy K. Lu: Massachusetts Institute of Technology

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract Current limitations to on-demand drug manufacturing can be addressed by technologies that streamline manufacturing processes. Combining the production of two or more drugs into a single batch could not only be useful for research, clinical studies, and urgent therapies but also effective when combination therapies are needed or where resources are scarce. Here we propose strategies to concurrently produce multiple biologics from yeast in single batches by multiplexing strain development, cell culture, separation, and purification. We demonstrate proof-of-concept for three biologics co-production strategies: (i) inducible expression of multiple biologics and control over the ratio between biologic drugs produced together; (ii) consolidated bioprocessing; and (iii) co-expression and co-purification of a mixture of two monoclonal antibodies. We then use these basic strategies to produce drug mixtures as well as to separate drugs. These strategies offer a diverse array of options for on-demand, flexible, low-cost, and decentralized biomanufacturing applications without the need for specialized equipment.

Date: 2018
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DOI: 10.1038/s41467-017-02587-w

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