Portable, On-Demand Biomolecular Manufacturing

Keith Pardee; Shimyn Slomovic; Peter Q Nguyen; Jeong Wook Lee; Nina Donghia; Devin Burrill; Tom Ferrante; Fern R McSorley; Yoshikazu Furuta; Andyna Vernet; Michael Lewandowski; Christopher N Boddy; Neel S Joshi; James J Collins

doi:10.1016/j.cell.2016.09.013

Portable, On-Demand Biomolecular Manufacturing

Cell. 2016 Sep 22;167(1):248-259.e12. doi: 10.1016/j.cell.2016.09.013.

Authors

Affiliations

¹ Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada.
² Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
³ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
⁴ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
⁵ Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
⁶ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
⁷ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Harvard-MIT Program in Health Sciences and Technology, Cambridge, MA 02139, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: jimjc@mit.edu.

PMID: 27662092
DOI: 10.1016/j.cell.2016.09.013

Abstract

Synthetic biology uses living cells as molecular foundries for the biosynthesis of drugs, therapeutic proteins, and other commodities. However, the need for specialized equipment and refrigeration for production and distribution poses a challenge for the delivery of these technologies to the field and to low-resource areas. Here, we present a portable platform that provides the means for on-site, on-demand manufacturing of therapeutics and biomolecules. This flexible system is based on reaction pellets composed of freeze-dried, cell-free transcription and translation machinery, which can be easily hydrated and utilized for biosynthesis through the addition of DNA encoding the desired output. We demonstrate this approach with the manufacture and functional validation of antimicrobial peptides and vaccines and present combinatorial methods for the production of antibody conjugates and small molecules. This synthetic biology platform resolves important practical limitations in the production and distribution of therapeutics and molecular tools, both to the developed and developing world.

Keywords: antibody mimetic conjugates; antimicrobial peptides; cell-free expression; decentralized biomanufacturing; freeze-dried; on-demand biosynthesis; portable molecular manufacturing; synthetic biology; vaccine antigens; violacein biosynthetic pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibody Formation*
Antimicrobial Cationic Peptides / biosynthesis*
Antimicrobial Cationic Peptides / genetics
Cell-Free System
Combinatorial Chemistry Techniques
Humans
Protein Biosynthesis
Synthetic Biology
Transcription, Genetic
Vaccines / biosynthesis*
Vaccines / genetics

Substances

Antimicrobial Cationic Peptides
Vaccines