Portable, On-Demand Biomolecular Manufacturing

被引:239
|
作者
Pardee, Keith [1 ]
Slomovic, Shimyn [2 ]
Nguyen, Peter Q. [3 ]
Lee, Jeong Wook [2 ,3 ]
Donghia, Nina [3 ]
Burrill, Devin [3 ]
Ferrante, Tom [3 ]
McSorley, Fern R. [4 ]
Furuta, Yoshikazu [2 ]
Vernet, Andyna [3 ]
Lewandowski, Michael [3 ]
Boddy, Christopher N. [4 ]
Joshi, Neel S. [3 ,5 ]
Collins, James J. [2 ,3 ,6 ,7 ,8 ,9 ]
机构
[1] Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON M5S 3M2, Canada
[2] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[3] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA
[4] Univ Ottawa, Dept Chem & Biomol Sci, Ottawa, ON K1N 6N5, Canada
[5] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA
[6] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[7] MIT, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[8] Harvard MIT Program Hlth Sci & Technol, Cambridge, MA 02139 USA
[9] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
关键词
FREE PROTEIN-SYNTHESIS; CELL-FREE PRODUCTION; BIOSYNTHETIC-PATHWAY; DIPHTHERIA-TOXIN; VACCINE; BIOLOGY; POLYPEPTIDES; VIOLACEIN; MOLECULES; PLATFORMS;
D O I
10.1016/j.cell.2016.09.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:248 / +
页数:24
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