A single shot of self-amplifying RNA can repair tissue damage from a heart attack, new research in pigs and mice shows.
It can take weeks or months to recover from a heart attack, but the new study explored a new way to increase the production of a natural heart-repairing hormone with a single injection. Although the shot has not yet been tested on humans, researchers believe it may one day offer hope for a faster recovery.
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ONE heart attack is often caused by a blocked artery that prevents oxygen-rich blood from reaching the heart muscle. While surgery can remove the blockage, the heart muscle itself must also recover from the lack of oxygen. If it does not heal quickly enough, scar tissue will take its place, which is less efficient at pumping blood and can trigger heart failure.
”Heart disease is still the number one killer in the United States,” said Ke Chenga biomedical engineer at Columbia University and senior author of the new study. Repairing heart muscle cells after a heart attack can reduce the risk of death from heart failure, but it comes with a challenge. ”It is very difficult to deliver drugs to the heart without invasive procedures,” Cheng told Live Science.
In the study, published March 5 in the journal ScienceCheng and his collaborators showed that a single injection of self-amplifying RNA (saRNA) into the muscle tissue of the hind leg could heal heart muscle cells in mice and pigs by increasing the levels of a hormone called atrial natriuretic peptide (ANP).
From studying mice, researchers learned that ANP levels are much higher in newborns than in adults—a difference they attributed to ANP playing a role in heart development. This inspired Cheng and colleagues to see if it was possible to temporarily increase ANP levels in adult mice to help heal the heart. “We wanted to see if we can supplement ANP with self-amplifying RNA,” Cheng said.
When injected, the saRNA instructs muscle tissue to produce a molecule called proANP, which enters the bloodstream and is converted to ANP when it reaches the heart.
The mechanism is similar to how mRNA vaccines work. Like mRNA, saRNA includes the instructions for making a protein. Both mRNA and saRNA degrade within days, but saRNA instructs the cell to make more copies of itself so it can continue to renew itself and produce protein for about four weeks.

The first saRNA-based COVID-19 vaccine was approved for use in Japan and Europebut saRNA has never been used in cardiac treatment before.
“I think this is a perfect use of saRNA,” said Anna Blakeneya biomedical engineer at the University of British Columbia who studies saRNA but was not involved in the research. She pointed out that mRNA doesn’t work for studies like this because it disappears so quickly. It is enough for vaccines to activate the immune system, but for applications that need larger amounts of protein, saRNA works better.
Although this new method of increasing ANP has not been tested in humans, it helps heart cells to recover in mice and pigs. Since saRNA is effectively a longer form of mRNA, it uses the same delivery system as COVID-19 vaccines, which bodes well for the safety of the injection itself. Nevertheless, future studies will still need to determine what dose of ANP is safe and effective in humans.
”We don’t yet know exactly what the mechanism would be that would have a benefit for patients,” said Dr. Dan Atar, a professor of cardiology at Oslo University Hospital who was not involved in the study. Previous studies treating heart attack patients with natriuretic peptides (such as ANP) did not help recovery, he noted, so this new single-shot delivery method needs to be proven in clinical trials.
Much more research is still needed for this potential treatment, including trials to confirm the mechanism, test the injection’s safety and monitor its effects. But if it passes these steps, it could offer a promising path to healing the heart after a heart attack.
Zhang, K., Tao, H., Zhu, D., Yue, Z., Hu, S., Wu, Y., Yan, N., Hu, Y., Liu, S., Liu, M., Vahl, TP, Ranard, LS, Cheng, X., Romanov, A., Liu, J., Zhang, SW, MC, Y. . . Cheng, K. (2026). Single intramuscular injection of self-amplifying RNA of Nppa to treat myocardial infarction. Science, 391(6789), edau9394. https://doi.org/10.1126/science.adu9394






