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Merck

Portable, On-Demand Biomolecular Manufacturing.

Cell (2016-09-24)
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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
β-Nicotinamide adenine dinucleotide, reduced disodium salt hydrate, ≥97% (HPLC)
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)
Sigma-Aldrich
Carboxy-terminal FLAG-BAP Fusion Protein
Sigma-Aldrich
Anti-Mouse IgG - Atto 655 antibody produced in goat, ~1 mg/mL IgG