Portable biological factories create pharmaceuticals

October 3, 2016, Cell Press

Pellets made from freeze-dried molecular components make it possible to "just add water" to create diverse compounds without the need for refrigeration. This portable and inexpensive platform, intended to help those far away from hospitals or even astronauts on the space station, could allow for the creation of pharmaceuticals, specialized therapies, and experimental biomolecules. The technology, developed by Harvard and MIT researchers, is presented September 22 in Cell.

"I think this opens up possibilities of creating a biotech equivalent of the chemistry kits many of us grew up with that consisted of powders and chemicals," says senior author James Collins, who runs a lab at the Wyss Institute for Biologically Inspired Engineering. "Now, we show that you can actually have freeze-dried DNA components and other biomolecules that can be used in an easy, low-resource way to explore the power of our technology."

Rather than freeze-drying the end molecules and re-hydrating them, the Collins Lab freeze-dries the molecular machinery for transcription and translation, which are then made into reaction pellets. After water is added to rehydrate the pellets, the gets to work creating the desired end molecule.

The technology is applicable in a wide variety of applications. For example, since antibodies are increasingly being used to treat microbial infections and diseases ranging from cancer to immune disorders, the researchers used their system to create a portable, modular toolbox for making designer antibodies against a variety of disease-relevant targets. This included one that could neutralize C. difficile bacteria, which cause fatal infections in people, and another that was able to target and kill .

The researchers also explored on-site vaccine production by testing the ability of the pellets to synthesize a vaccine against diphtheria. The vaccine is sensitive to both heating and freezing, making its storage and global distribution challenging, and the ability to rapidly synthesize it on site would thus be an important advance. The scientists found that the pellet-synthesized vaccine was able to elicit a protective response in mice.

"We showed that you could get an appropriate biological response," says Collins. "We're not developing novel vaccines, but we're showing that if we can encode the antigens in DNA, then we can harness that ability and have the vaccines in an easy-to-ship and -store format."

This new approach to biomolecular manufacturing costs an average of $0.03 per microliter, making it about 10 times less expensive than its commercial counterpart, although the exact cost can vary depending on the molecules being manufactured. The reaction pellets can be transported at room temperature and may provide a solution for problems doctors and scientists may face when they lack adequate refrigeration facilities. Additionally, because, for most uses, the pellets have simple instructions for use—"just add water"—very little training would be required for therapeutic use.

Collins and his team are optimistic about other potential uses of this technology, including futuristic applications for long-term medical treatment during space travel. Although Collins admits that scalability may be an issue with certain molecules that are not immediately amenable to the freeze-drying process, his team is discussing the next steps they can take with this technology.

In addition to expanding the process to work with more complex molecules, his lab is looking to adapt the platform so that it can be used in field work, to extend the platform to educational applications, and to determine how the technology could be used for additional small-molecule production.

Explore further: To produce biopharmaceuticals on demand, just add water

More information: Keith Pardee et al, Portable, On-Demand Biomolecular Manufacturing, Cell (2016). DOI: 10.1016/j.cell.2016.09.013

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