Vaccines, Supercharged

Two BU doctoral students investigating RNA may have found more exciting results than they expected.

Joshua McGee (ENG’24,’24) and Jack Kirsch (ENG’23,’23) were tinkering with RNA sequences—strands of ribonucleic acid—to see if small tweaks to their nucleotides could lead to improved drugs and vaccines.

Instead, they found a way to advance vaccines, gene therapy, and cancer treatments using self-amplifying RNA (saRNA), a type of RNA that repeatedly replicates its programmed instructions, producing more proteins than normal.

Working with chemist and biomedical engineer Mark Grinstaff, who is a William Fairfield Warren Distinguished Professor, and Wilson Wong, an associate professor of biomedical engineering, McGee and Kirsch identified a way to alter the chemical structure of saRNA that makes it a more powerful, efficient vaccine.

This development kicked off a yearlong, multidisciplinary project that spanned Grinstaff’s chemistry lab and Wong’s genetics engineering lab; it also enlisted Florian Douam, a Peter Paul Career Development Professor and assistant professor of virology, immunology, and microbiology at BU’s National Emerging Infectious Diseases Laboratories.

While standard mRNA COVID vaccines tell cells to produce a spike protein that mimics the real virus, saRNA keeps going, repeating instructions to the cell, multiplying its effect (with less medicine), and prompting the immune system to remember how to fight the virus for a longer period of time.

There’s more testing to be done, but results are promising. It’s possible that saRNA could be programmed to produce a missing gene or replace a defective one. It could also be used in treating lung, breast, and other cancers by compounding the effects of an anticancer drug with a lower, less harmful dose.

The National Science Foundation (NSF) awarded Grinstaff a $3 million Trailblazer Engineering Impact Award to continue exploring saRNA technology. It is a discovery that could, as the NSF abstract puts it, “fundamentally change the genetic engineering paradigm.”