BU's Mark Grinstaff one of six researchers to receive NSF Trailblazer Engineering Impact Awards

A new technology that could revolutionize vaccines has garnered Boston University’s Mark Grinstaff one of just six inaugural Trailblazer Engineering Impact Awards from the National Science Foundation (NSF). The $3 million award will allow Grinstaff to explore new possibilities in the engineering of messenger RNA for vaccines with reduced side effects, along with other applications.

“The vaccine we’ve created is effective at a 100-fold lower dose” than is currently common, says Grinstaff, a William Fairfield Warren Distinguished Professor. Building on these early results, which have upended conventional wisdom, Grinstaff will lead an interdisciplinary BU team in further developing and testing the technology over the next three years. “This award might open up new avenues of treatment that are not available today.”

Messenger ribonucleic acid (mRNA) technology gained fame as a key component in the vaccines that halted the COVID-19 pandemic. Adding modified mRNA to a cell can trigger the production of proteins, including antibodies that fight bacteria and viruses.

“The messenger RNA vaccine is quite effective,” says Grinstaff, who is also a professor of biomedical engineering in the College of Engineering and a professor of chemistry in the College of Arts & Sciences. “However, there are some limitations to that technology. The amount of protein produced, which would then bring about the immune protection, is quite low. And the time span during which that protein is produced is very short. Thus, we have to re-dose, or we have to use large doses, to make the vaccine effective.”

Grinstaff’s doctoral students Joshua McGee (ENG’24) and Jack Kirsch (ENG’23) began studying one alternative: self-amplifying RNA (saRNA). McGee calls it “a form of RNA that includes machinery to make more copies of itself—sort of like delivering a printed message along with a photocopier.” That means a smaller dose of vaccine could last a lot longer—or so researchers have been hoping for years. Unfortunately, for various reasons, study after study seemed to show that the saRNA method was a pipe dream.

Grinstaff’s team tackled it anyway. After much iteration, they introduced a kind of modified cell building block, called an NTP, into an saRNA. When formulated as a vaccine, this combination protected against lethal SARS-CoV-2 (the virus that causes the COVID-19 disease) in live animal models at dramatically lower dosage levels than required of standard mRNA vaccines.

“And if we have low doses, that might mean fewer side effects,” says Grinstaff. “And maybe even multiple vaccinations in a single shot, or one vaccine that would protect against all the current variants.” The team published their findings in Nature Biotechnology.

“saRNA could revolutionize vaccines and gene/cell therapy, making them more potent, less expensive, and more accessible,” says Grinstaff’s collaborator Wilson Wong, an ENG associate professor of biomedical engineering.

Beyond vaccines, the technology carries potential implications for combating genetic diseases and cancer, which Grinstaff and colleagues will also study. “We have a way to produce a protein with an intramuscular injection,” says Grinstaff. “It could be a protein that’s missing in your body because of a genetic disease.”

Much work remains, but the experience has already taught McGee a powerful lesson. “It is OK to challenge widely held scientific ideas,” he says. “I am fortunate for the support that Mark provided in allowing us to explore this research direction that was likely to fail, per the 10-plus published articles that said so. It is through the process of challenging ideas that innovation is born.”

In addition to McGee, Kirsch, and other doctoral students in BU’s biomedical engineering, chemistry, and virology, immunology, and microbiology (VIM) programs, Grinstaff and Wong are working with Florian Douam, an assistant professor of VIM programs, and a Peter Paul Career Development Professor at BU’s Chobanian & Avedisian School of Medicine, and a researcher at the BU National Emerging Infectious Diseases Laboratories. Although the NSF grant is an individual award for Grinstaff, it nonetheless recognizes the groundbreaking and ongoing work of a collection of experts. “It’s quite nice to see all of these people come together over a single theme of research,” says Grinstaff. “That’s one of the strengths of BU.”

Still, Grinstaff is the right researcher to receive the NSF award, his colleagues say. “Mark is a visionary pioneer who has made seminal contributions to multiple disciplines, such as biomaterials, drug delivery, and nanotechnology,” says Wong. “He is also a proven leader who can bring our community together to do great science. He is precisely the type of leader and trailblazer that we should celebrate, and I am proud to be his colleague and collaborator.”

“Through the Trailblazer program, NSF is enabling innovative researchers to explore new directions beyond today’s frontiers,” says Susan Margulies, NSF assistant director for engineering. “Our investment will lead to engineering impacts in biotechnology, sustainability, quantum technology, and other areas that ultimately strengthen US resilience and competitiveness.”