By Sarah Hansen ’15, M.S., Biological Sciences
The Defense Advanced Research Projects Agency (DARPA) recently renewed a grant for approximately eight million dollars over two years for a team at UMBC’s Center for Advanced Sensor Technology (CAST). The team is developing a portable device the size of a briefcase that can produce therapeutic proteins, such as insulin, in only a few hours and in small batches. The device would be critical in situations where medical supply lines have been cut, such as in war zones or following natural disasters. The project is known as BioMOD, for “biologically-derived medicines on demand.”
The new device, which could eventually replace the current centralized model of pharmaceutical production, is like “going from a mainframe computer to a laptop,” said Govind Rao, CAST director and professor of biochemical, chemical, and environmental engineering (CBEE) at UMBC. “It empowers people in ways that are unimaginable,” he said. The device would first be used in hospitals, but the team’s vision includes eventual home use.
UMBC is the lead of a consortium including the Ohio State University (protein purification), Thermo Scientific (cell-free expression system), and Latham BioPharm (system integration), and there are approximately 30 team members across all sites. UMBC teammates come from several departments: CBEE, Computer Science and Electrical Engineering, Mechanical Engineering, Chemistry, and Biological Sciences.
During the first two years of the grant, the team showed that their general approach can work. A bioreactor approximately the size of half of a soda can contains cellular extracts from Chinese hamster ovarian (CHO) cells. CHO cells are “an industry workhorse for producing pharmaceuticals,” said Rao. The beauty of this device is that the cellular extracts are “essentially the cell minus the nucleus,” Rao said. That means the tricky task of keeping cells alive isn’t necessary, but the protein-production machinery is ready to go when one adds DNA coding for the desired protein product. The bioreactor builds the desired protein in two to four hours. The short time scale also reduces contamination risk. The next step is purification, where you “fish the product out” of the cellular slurry in the bioreactor, Rao explained. The third step, polishing, is an even finer process to remove any remaining impurities.
The team knows the device works, so “now it’s the real deal to show that it works in a robust enough fashion to produce molecules of the necessary purity to safely administer to a human,” Rao said. The team will be carrying out “an exhaustive amount of validation” to show that the protein product is of similar “purity, potency, and structure to that made by a conventional commercial process,” Rao explained.
This next two-year phase will stop short of clinical trials, however. The team is looking for commercial partners to help support extraordinarily expensive clinical trials once they thoroughly validate the prototype and procedures in the lab.
Rao appreciates working with DARPA. “They are not afraid of risks, and they have an extraordinary tolerance for failure. That allows us to try bold things that we ordinarily wouldn’t,” he said.
That tolerance for failure has certainly been tested. This spring, a key piece of equipment used for validation had consistent problems. It required a major overhaul and new training for CAST team members, plus it was out of operation for several weeks. I experienced the frustrations of the scientific process firsthand in my role as a CAST graduate assistant whose primary responsibility was this particular instrument. Before I left, though, the machine was up and running again. It hadn’t produced any important results yet, but Rao was quick to emphasize that “every little bit is important. It’s all about the team.”
It has its challenges, like all worthwhile endeavors, but, “This is going to be making history,” Rao said. “Someday 20 years from now, when you’re injecting yourself with a drug you made yourself, you’ll say, ‘I was there.’”