Freeze-dried, easily reconstituted cellular machinery can free biomanufacturing from the cold chains that are needed to preserve live cells. Instead, tiny pellets containing enzymes, ribosomes, RNA, and DNA can be stored at room temperature, taken where needed, and unleashed simply by adding water. Basically, the cell-free extracts can enable on-the-spot biomanufacturing for healthcare workers, military personnel, and educators—as well as travelers and adventurers who would appreciate unusually sophisticated first-aid kits. Imagine “smart bandages” that would detect an infection and then begin producing the appropriate antimicrobial peptide to treat the infection.

The freeze-dried pellets were devised by MIT researchers led by James Collins, Ph.D., a professor of biological engineering. Over the past few years, Dr. Collin’s team has shown that synthetic biology can be used to perform the work of cells, without the cells. For example, the team was able to extract and freeze-dry cellular components needed to produce drugs or biofuels. It began by freeze-drying materials onto paper or other materials.

In its most recent work, Dr. Collin’s team has not only done without the cells, it has also done without the paper substrate. Now the cellular components are simply freeze-dried into pellets, which remain stable for at least a year. To activate protein production, the researchers add water to rehydrate the pellets. Different combinations of pellets—protein machinery pellets and DNA pellets, for example—to accomplish different syntheses.

Details of the new work appeared September 22 in the journal Cell, in an article entitled, “Portable, On-Demand Biomolecular Manufacturing.” The article describes how to do without specialized equipment and refrigeration facilities, which are usually needed to support biomanufacturing production and distribution. Building and maintaining such facilities is challenging in the field and in low-resource areas.

“We present a portable platform that provides the means for on-site, on-demand manufacturing of therapeutics and biomolecules,” wrote the authors. “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.”

The authors described how they demonstrated their approach with the manufacture and functional validation of antimicrobial peptides and vaccines. The authors also presented combinatorial methods for the production of antibody conjugates and small molecules.

“This synthetic biology platform,” the authors concluded, “resolves important practical limitations in the production and distribution of therapeutics and molecular tools, both to the developed and developing world.”

In the current study, the researchers produced small proteins that could be used as a diphtheria vaccine, as well as antimicrobial peptides. They also programmed the pellets to generate enzymes that form a multistep metabolic pathway that synthesizes a complex drug known as violacein, which has anticancer and antibiotic activity. Finally, for diagnostic applications, the researchers used the pellets to produce several different types of antibodies, including one that can detect the bacterium Clostridium difficile, which can produce severe inflammation of the colon.

“It's a modular system that can be programmed to make what you need, on the spot,” said Dr. Collins. “You could have hundreds of different DNA pellets you can add in the field.”

“Collins and colleagues paint a future where freeze-dried, cell-free biomanufacturing platforms can be used to synthesize therapeutics, vaccines, and biochemicals on demand, without the need for a cold [supply] chain,” added Michael Jewett, Ph.D., an associate professor of chemical and biological engineering at Northwestern University, who was not involved in the research. “By moving manufacturing from the factory to the front lines, we might be able to provide patient-specific medicines where medicines are not available now.”

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