Just-in-time therapeutics manufacturing project receives additional DARPA funding

Posted: July 28, 2015

Student Tzu-Chiang Han and Associate Professor David Wood in the lab purifying recombinant biopharmaceutical proteins from a mammalian cell culture supernatant.
Engineers at The Ohio State University are another step closer in their efforts to help develop a portable briefcase-sized device capable of producing protein-based biopharmaceuticals on demand, thanks to renewed funding from the Defense Advanced Research Projects Agency (DARPA).

David Wood, associate professor of chemical and biomolecular engineering, received an additional $500,000 to adapt his intein-based protein purification system into a portable device that could produce and purify a ready-for-delivery therapeutic protein in just a few hours. The funding is part of a larger $8 million dollar DARPA renewal grant to a team led by the University of Maryland, Baltimore County (UMBC) as part of the agency’s Biologically-derived Medicines on Demand (Bio-MOD) project.

By producing therapeutic proteins more quickly and efficiently via a cell-free system, the device could provide critically needed medicines on the battlefield or following natural disasters. 

Protein-based drugs, which are used in the treatment of diabetes, cancer and rheumatoid arthritis, among others, currently take weeks to manufacture and ship. 

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, principal investigator and director of UMBC’s Center for Advanced Sensor Technology. “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.

During the first two years of the contract, the team created a proof of concept to demonstrate that their general approach can work. For the next phase, researchers will need to prove that the device is able to produce molecules of the necessary purity to safely administer to humans. The project will stop short of clinical trials. Researchers are looking for commercial partners to help support the extraordinarily expensive clinical trials once they thoroughly validate the prototype and procedures in the lab.

“The process basically involves expressing a protein in a cellfree system very quickly, then capturing the protein and purifying it,” Wood explained. “My part is capturing the protein.”

Wood was recruited to participate in the project because of the innovative intein-based purification system he developed as a graduate student. It provides a general method that can be applied to any target protein, making it a single core platform compatible with the dozens of products the device will eventually produce. 

Wood’s technology creates self-cleaving affinity tags, which enable simple and cheap protein purification. It’s used in the initial capture step of the device’s manufacturing process during which 90 to 95 percent of the purification is completed and is followed by polishing steps to further purify the drug. 

Wood’s group has already created a set of inteins and showed that they work well to purify a variety of proteins in a laboratory scale environment. Over the next two years, the Buckeye engineers will be focused on using the technology to purify six model proteins and incorporate it into the miniaturized device.

Although the technology is being researched and developed with a focus on military use, it could eventually benefit the civilian patient population.

"The ability to produce single-dose protein drugs at minimal expense will allow for the development of highly specific therapeutics for very small patient populations,” Wood said. “These drugs have been impossible to develop economically in the past, but this device may enable truly personalized medicine, providing relief to those who have been previously left untreated." 

Read more about the research via the University of Maryland, Baltimore County, BioProcess Online and Buckeye Engineering (2013 article).

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