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Nat Commun. 2018 Jan 8;9(1):77. doi: 10.1038/s41467-017-02587-w.

Versatile and on-demand biologics co-production in yeast.

Author information

1
Synthetic Biology Group, Department of Biological Engineering and Electrical Engineering & Computer Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
2
Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
3
The Broad Institute of MIT and Harvard, Cambridge, MA, 02139, USA.
4
Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
5
Synthetic Biology Group, Department of Biological Engineering and Electrical Engineering & Computer Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. timlu@mit.edu.
6
Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. timlu@mit.edu.
7
The Broad Institute of MIT and Harvard, Cambridge, MA, 02139, USA. timlu@mit.edu.

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.

PMID:
29311542
PMCID:
PMC5758815
DOI:
10.1038/s41467-017-02587-w
[Indexed for MEDLINE]
Free PMC Article

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