A New Type of RNA Could Revolutionize Vaccines and Cancer Treatments

Original article from The Brink by Jessica Collarossi, September 9, 2024.

It all started in the lab. Two Boston University doctoral students, Joshua McGee (ENG’26) and Jack Kirsch (ENG’23), were creating and testing different types of RNA—strands of ribonucleic acid, built from chains of chemical compounds called nucleotides, that help carry out genetic instructions in cells. They were determined to see if RNA sequences crafted with small changes to their nucleotides can still work. After running dozens of experiments, they hit a dead end.

“At first, it was a failure,” McGee says.

Decades of research have uncovered the mysteries of RNA in living cells. Without it, our cells couldn’t perform fundamental tasks, like constructing other cells, carrying amino acids from one part of the cell to the other, or mounting immune responses to viruses.

But, more recently, scientists have figured out how to harness RNA to make treatments aimed at fighting genetic diseases and cancer. They’ve also learned how to use messenger RNA (mRNA) to make COVID-19 vaccines. The experiments that McGee and Kirsch perform are aimed at using RNA to deliver lifesaving drugs and create more effective vaccines than we have today.
Working alongside Mark Grinstaff, BU’s William Fairfield Warren Distinguished Professor of biomedical engineering and chemistry, and Wilson Wong, a College of Engineering associate professor of biomedical engineering, they started talking about what to do next—and what to do with the chemical components left over from the initial experiments. They decided to focus on modifying the chemical structure of a lesser-known type of RNA, called self-amplifying RNA (saRNA), which is manufactured in the lab and replicates itself multiple times in a cell to produce a higher number of the proteins it’s programmed to make.
The new method worked: their modified saRNA was replicating itself in a petri dish.


Grinstaff, Wong, and the team collaborated closely with Florian Douam, a BU Chobanian & Avedisian School of Medicine assistant professor of virology, immunology, and microbiology and a core faculty member at NEIDL. He and his team performed a study—called a “viral challenge”—to evaluate if a COVID-19 vaccine built with the modified saRNA technology could protect mice more effectively against severe COVID-19 disease than earlier saRNA and mRNA vaccines.

“The viral challenge aspect was particularly important,” Douam says. “It exposed how a very low dose of this novel saRNA technology is able to protect mice against lethal disease much more effectively than traditional saRNA and mRNA COVID-19 vaccines at a similar dose.” Douam says that the new vaccine, which incorporates modified nucleotides called m5C (5-methylcytidine), also triggered very low levels of inflammation upon vaccination comparable to mRNA vaccines.
“There is still plenty of work to be done to unveil all of the advantages of this technology over other existing RNA vaccine approaches,” Douam says. But this was a promising start.

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