mRNA vaccines just won a Nobel Prize. Now they’re ready for the next act.

The other reason is that researchers can add in mRNA for many different flu strains to create a vaccine that might provide broader protection. Last year, a team at the University of Pennsylvania tested an mRNA vaccine containing antigens from all 20 known influenza subtypes that infect humans. In mice and ferrets, the vaccine protected against strains that matched the vaccine and strains that didn’t. This year, the National Institutes of Health launched a clinical trial to test another mRNA flu vaccine that doesn’t contain multiple antigens, but is designed to elicit a response to a portion of the virus that isn’t as likely to change from year to year.

Flu is just the beginning. The list of diseases for which mRNA vaccines are being developed goes on (and on and on): malaria, HIV, Zika virus, Epstein-Barr virus, cytomegalovirus, herpes, norovirus, Lyme disease, Nipah virus, C. difficile, hepatitis C, leptospirosis, tuberculosis, shingles, acne, chlamydia, and many others. 

But wait! There’s more. mRNA could be a powerful way to treat diseases, not just prevent them. In fact, it was originally envisioned as a therapeutic. mRNA-based therapies for cancer have been in trials for a decade. The idea here is to provide mRNA that codes for proteins on the surface of the tumor. The immune system would then learn to recognize these antigens, and it can more effectively detect and attack cancer tissue. 

Companies are also working on mRNA therapies for rare diseases, like cystic fibrosis. People with this disease have mutations in a gene called CFTR, the cystic fibrosis transmembrane conductance regulator. These mutations mean that the CFTR protein, which helps water move in and out of cells, doesn’t function correctly, leading to sticky mucus that clogs the lungs and causes recurring respiratory infections.

Vertex, in collaboration with Moderna, has developed mRNA that is designed to be inhaled. Once inside the lungs, cells translate the code into functional CFTR. Late last year, the Food and Drug Administration (FDA) gave Vertex the green light to launch a trial to test mRNA for cystic fibrosis. Moderna has also launched clinical trials to test therapies for methylmalonic acidemia, a disease that affects the function of the liver, and propionic acidemia, a rare metabolic disorder.

Not all of these efforts will succeed. In fact, many won’t. But the mRNA bonanza is sure to yield some wins. When Karikó and Weissman made their breakthrough discovery in 2005, “I told Kati our phones are going to ring off the hook,” Weissman said in an interview with Boston University’s alumni magazine in 2021. “But nothing happened. We didn’t get a single call.” Today, I think it’s safe to assume their phones won’t stop ringing.