Portable, On-Demand Biomolecular Manufacturing.
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.
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S 3M2, Canada.
Keith
K
Pardee
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Shimyn
S
Slomovic
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Peter Q
PQ
Nguyen
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.
Jeong Wook
JW
Lee
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Nina
N
Donghia
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Devin
D
Burrill
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Tom
T
Ferrante
Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
Fern R
FR
McSorley
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Yoshikazu
Y
Furuta
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Andyna
A
Vernet
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Michael
M
Lewandowski
Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
Christopher N
CN
Boddy
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
Neel S
NS
Joshi
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.
James J
JJ
Collins
D000818:Animals; D000917:Antibody Formation; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis* / Q000235:genetics; D002474:Cell-Free System; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D014176:Protein Biosynthesis; D058615:Synthetic Biology; D014158:Transcription, Genetic; D014612:Vaccines / Q000096:biosynthesis* / Q000235:genetics
D023181:Antimicrobial Cationic Peptides; D014612:Vaccines
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