Simply Add Water: On-Demand Production of Drugs and Vaccines

Rehydrating freeze-dried cellular components produces useful proteins.

Tiny freeze-dried pellets containing cellular extracts can activate protein production, simply by adding water and DNA, a study published in Cell found.

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

The pellets, which carry dozens of enzymes and other molecules extracted from cells, can be stored for an extended period of time at room temperature. Since the pellets are only a few millimeters in diameter, researchers believe that they could easily be carried by health care workers, soldiers, or astronauts who are going to remote areas.

“It could be used in a very simple carry kit for health care workers going in the field in developing regions,” Collins said. “We think it could be very useful for the military, when you’re going out on a mission in the field, or for hikers and athletes going for long hauls. You could even have it in the back of your car as an expanded first aid kit.”

Previously, Collins and others in the synthetic biology field designed cells that can perform numerous functions, such as producing drugs or biofuels. However, over the past few years, Collins has shown that this design type can also be done outside of cells, through the process of extracting necessary cellular components and freeze-drying them onto paper or other materials.

“The cell-free extracts consist of a few dozen enzymes, DNA, and RNA, as well as ribosomes and other molecular machines leading to transcription and translation,” Collins said.

However, in the current study the research team decided to take the paper out of the equation, and instead the extracts were freeze-dried into pellets, remaining stable for at least a year. Authors noted that the new approach may be useful in generating a wide array of products, including both drugs and molecules that could be used to diagnose illness.

In the study, researchers chose to produce small proteins that could be used as a diphtheria vaccine, and antimicrobial peptides, which could potentially fight bacterial infections. Additionally, researchers programmed the pellets to generate enzymes that form a multistep metabolic pathway that synthesizes the complex drug called violacein, which has antibiotic and anticancer activity.

For diagnostic applications, the pellets were used to produce different types of antibodies, including one that can detect Clostridium difficile, a bacterium that can produce severe inflammation in the colon.

Overall, researchers believe that the novel approach could prove to be easier to use than live cells to generate biopharmaceuticals. This is because the freeze-dried pellets are easy to store and ship and they don’t require refrigeration.

“Collins and colleagues paint a future where freeze-drive, cell-free biomanufacturing platforms can be used to synthesize therapeutics, vaccines, and biochemical on demand, without the need for a cold [supply] chain,” said Michael Jewett, associate professor at Northwestern University, who was not involved in the study. “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.”

Besides being used in military, health care, and other settings, study authors believe that the pellets could also be incorporated into educational tools.

“The biotech equivalent of a chemistry kit,” Collins said. “You could envision using these pellets to allow students to conduct synthetic biology experiments at home, or in middle schools and high schools.”

Study authors noted that they plan to pursue the integration of the pellets into smart bandages that would be able to detect an infection, and then begin producing the correct antimicrobial peptide to treat that infection.