U.S. President Joe Biden announced on Aug. 23 that Emory University will receive a $24.8 million cooperative agreement from the newly-established Advanced Research Projects Agency for Health (ARPA-H). Emory is the first-ever recipient of ARPA-H funding, according to Assistant Professor in the Department of Medicine Matthew Woodruff.
Philip Santangelo, who is a professor in the Wallace H. Coulter Department of Biomedical Engineering at Emory and the Georgia Institute of Technology, is leading the project, using mRNA technology to create new therapeutics to combat diseases, including cancer and facilitate organ transplants.
The project will receive funding for three years. Santangelo has worked on developing mRNA technology and said it has become clear that mRNA technology can help fight “chronic or systemic dysregulation of the immune system.”
mRNA technology can control gene expression within cells, according to Santangelo. He believes mRNA is the best way to address issues of compromised immune systems because mRNA does not change DNA, making it a temporary fix.
Over the course of a month, Santangelo and his team put together a proposal with around 400 pages for ARPA-H to review.
“Both the cost proposal and the science are very detailed,” Santangelo said. “So for 30 days, pretty much you eat, sleep and breathe that.”
Professor of Surgery Christian Larsen, Emory Vaccine Center Director Rafi Ahmed and Mason I. Lowance Professor of Medicine and Pediatrics Ignacio Sanz will lead research under Santangelo as part of the project. The group will also collaborate with researchers from the University of Georgia and Yale University (Conn.).
“I’m not an expert in everything,” Santangelo said. “We needed the right group, but they also needed to be committed to doing this because you have to respond, you have to move, you have to move quickly.”
Larsen will focus on applying Santangelo’s mRNA technology to decrease organ transplant rejection. According to Larsen, organ recipients must take immunosuppressants indefinitely once they receive the new organ, but the drugs compromise the immune system and increase a recipient’s chances of getting sick. Larsen hopes his lab will allow organ recipients to receive mRNA immunotherapy instead of taking immunosuppressants.
Professor in the Wallace H. Coulter Department of Biomedical Engineering at Emory and the Georgia Institute of Technology Phillip Santangelo believes that mRNA technology could be the key in developing new therapeutics for various diseases. Courtesy of Georgia Institute of Technology
“The goal [is] that we’re trying to use this mRNA technology is to silence the immune response specifically against the proteins from the donor,” Larsen said. “The goal of that would be to prevent the development of antibodies against your donor, and antibodies against your donor organ can lead to accelerated failure and death.”
Ahmed’s research uses Santangelo’s mRNA technology to reverse “T-cell exhaustion.” T-cells become dysfunctional after long battles with chronic diseases and cancer, Ahmed explained, making them less effective in fighting against infected cells.
“These killer cells are the most important mechanism of eliminating either virally infected cells or tumor cells,” Ahmed said.
PD-1 blockades are used to “reawaken” T-cells and fight T-cell exhaustion but are only successful in 20% to 30% of cancer patients, creating a need for new T-cell-aiding therapies, according to Ahmed.
Sanz will work alongside Woodruff, performing autoimmune modeling with humans, while Woodruff will work with mice. Sanz’s lab has been working with B-cells, which are immune cells that destroy pathogens and other foreign substances that enter the body to fight infections, for the last 10 to 15 years.
Woodruff hopes Sanz’s research will create a more robust immune response by modifying B-cells with mRNA technology.
The feasibility of mRNA-based vaccines has expanded since the Pfizer-BioNTech and Moderna COVID-19 vaccines used mRNA technology, according to Woodruff. He added that while mRNA technology has been around for many years, it was not tested in humans until the pandemic created a pressing need and demonstrated that mRNA vaccines are feasible.
“We could develop the mRNA vaccines much, much faster than we would have been able to develop the protein vaccines,” Woodruff said.
Santangelo, Woodruff, Larsen and Ahmed agreed that the funding for this research is monumental. Larsen explained that the money ARPA-H is awarding Emory is unique because this project is “high-risk, high-reward,” as opposed to funding from the National Institutes of Health, which Woodruff said is typically based on “a really long-standing foundation of support [for] potential success.”
“Investigators are pretty excited to sort of be on the front end of where the federal government is trying to drive research in the United States,” Woodruff said. “We’re looking forward to getting started on it. We’ll see how it goes over the next three years.”
Spencer Friedland (26C) is from Long Island, New York and is the Emory Wheel's Managing News Editor. He is a Philosophy, Politics and Law major and has a secondary major in Film. Spencer is also a part of the Franklin Fellows program at Emory.
