Vaccines are just the beginning for RNA. The technology is being tested on heart and liver diseases.

Seven people who underwent heart-bypass surgery recently in Europe volunteered to receive an additional treatment: injections of messenger RNA.

This was not one of the COVID-19 vaccines, in which the RNA code is used to teach the recipient’s immune system. Instead, the RNA for the surgery patients was designed to heal their hearts — by promoting the growth of new blood vessels.

The study, a collaboration between drugmakers AstraZeneca and Moderna, is among dozens underway to harness the potential of RNA. Some of them started before the pandemic, but with the real-world success of the vaccines, they have now picked up steam.

At Duke University Medical Center, researchers are testing a different RNA-based drug from Moderna in patients with propionic acidemia, a rare disorder in which the liver is unable to break down certain amino acids and fats. Others are testing messenger RNA against a variety of cancers.

And, of course, RNA is being used to make more vaccines. Among those being tested are vaccines against Zika virus, respiratory syncytial virus (RSV), cytomegalovirus, and the flu.

All these efforts rely on RNA’s ability to carry the recipe for proteins, the building blocks of life. In a vaccine, the protein is a harmless fragment of the virus in question, allowing the recipient’s immune system to practice in the event of infection. In the other drugs, the RNA can prompt patients’ cells to make beneficial proteins that they are unable to make themselves.

It is too soon to say how well the various non-vaccine RNA drugs will work, said cardiologist Howard J. Eisen, a medical director at the Penn State Heart and Vascular Institute, who has been following the research. Among other issues: RNA degrades quickly (remember how the COVID vaccines require cold storage?), so it has to be delivered to the right cells in a timely fashion.

Yet the potential, he says, is vast.

“It’ll revolutionize medicine, I think.”

In the heart study, patients experienced no serious side effects as a result of the injections, the drugmakers reported in November. That was little surprise, given that billions have now been injected safely with RNA vaccines, said Eisen, who was not involved with the study.

But with just seven people (and another four who received placebo injections), the study was too small to draw conclusions about the drug’s effect on heart function. Larger studies are planned.

The RNA carries the recipe for a protein called VEGF-A, a growth factor involved in forming new blood vessels. The hope is that the patients would experience an improved “ejection fraction” — a measure of how much oxygenated blood is pumped with each heartbeat. Yet previous studies, in which researchers have sought to boost that protein with a different approach called gene therapy, have met with limited success.

Likewise, tests of the RNA-based drug for propionic acidemia are in the early stages, as are studies of RNA treatments for other metabolic diseases.

What’s clear is that new approaches for these liver disorders are sorely needed, said Dwight Koeberl, who is overseeing the Duke University site for Moderna’s propionic acidemia trial.

For now, patients with that disease must severely limit or avoid intake of meat, dairy, and nuts — or else their bodies build up toxic byproducts that lead to neurological and heart damage, among other complications. To compensate for this restricted diet, they must drink a special formula with vitamins and other supplements. And even so, some eventually need a liver transplant.

Koeberl, a professor of pediatrics at Duke University School of Medicine, also has studied the use of gene therapy to treat such patients. That approach is a long-term fix, as the instructions for making the corrective proteins are delivered inside the nucleus of the person’s cells (whereas RNA is transient, degrading within days — meaning that some treatments would need to be administered multiple times).

But as with the gene therapy treatments for heart disease, gene therapy for metabolic disorders remains a work in progress. One hurdle with gene therapy is that it is typically delivered inside the recipient’s cells with a virus, which can be defeated by the immune system, Koeberl said.

RNA-based therapies, on the other hand, are typically packaged in tiny droplets of oily molecules called lipids, as with the COVID vaccines. These lipid nanoparticles do not enter the cell nucleus. They need to penetrate only the outer cell membrane for the RNA to fulfill its mission, and they do so with ease. Koeberl was attracted by the possibility of a more straightforward solution.

“My interest is in trying to help these patients with something sooner rather than later,” he said.

Many, if not most, of the RNA drugs being tested are vaccines, to judge from a search of clinicaltrials.gov, a listing of clinical studies maintained by the U.S. National Library of Medicine.

Compared to traditional vaccines, one advantage of the RNA approach is that the genetic instructions can be quickly updated to match emerging threats. Pfizer and BioNTech, for example, already are developing a vaccine to match the omicron variant of the coronavirus, though widescale production still takes time. The European Union has ordered 180 million doses of this modified vaccine, expected to be available by March.

Next-generation RNA vaccines may also have the advantage of requiring lower doses. That’s the idea behind a flu vaccine in development by Seqirus, which has U.S. operations in Summit, N.J., and is a subsidiary of CSL Limited, based in Melbourne, Australia.

The RNA in that vaccine is “self-amplifying,” meaning that it consists of two elements: the genetic recipe for making flu proteins that stimulate an immune response, as well as instructions to make multiple copies of that recipe. In theory, that would mean a lower dose of such a vaccine could be just as effective, yet with a lower rate of side effects. Seqirus has been studying this approach in animal models for years, and it plans to test this type of flu vaccine in human volunteers during the second half of 2022.

Patient support groups have been watching the development of messenger RNA with great interest, whether the drug is being used to prevent disease, as with the vaccines, or to treat it.

Many advocates were aware of the potential for RNA treatments long before the COVID vaccines came out. Among them is Kathy Stagni, executive director of the Organic Acidemia Association, which provides support for patients with propionic acidemia and others.

She said she has been setting the record straight every time she hears someone claim that the technology behind the COVID vaccines was “rushed.”

“This is something they’ve been working on for a long time,” she said.

Eisen, the Penn State cardiologist, was working at the University of Pennsylvania decades ago when Penn scientist Katalin Karikó was doing some of the early experiments that would set the stage for the vaccines.

She was not working on vaccines at the time, but on using messenger RNA to treat heart disease. Now that the technology has matured, AstraZeneca and Moderna are tackling heart disease once again.

“In essence,” Eisen said, “it has come full circle.”