��ѿ��ý

March 31, 2026

Using RNA to treat heart attacks

Image

Pro-ANP is an injury-responsive protein that helps promote heart repair in newborn mice. High levels of pro-ANP are seen around injured heart muscle 3 days after a heart attack (yellow, right) compared with a healthy newborn mouse heart (left). Heart muscle cells are shown in magenta and cell nuclei are shown in cyan.

Cheng Lab/Columbia University

More than 800,000 people have heart attacks each year in the United States. Heart attacks occur when not enough blood flow reaches part of the heart. This kills the cells there, which can permanently impair heart function.

Doctors currently treat heart attacks by restoring blood flow to the affected area as quickly as possible. This requires an invasive procedure that must be done in a hospital. While this can limit the damage to the heart, the damage can’t usually be repaired.

A team of NIH-funded researchers led by Dr. Ke Cheng of Columbia University set out to develop a minimally invasive therapy to help the heart recover from a heart attack. Their research was published on March 5, 2026, in Science.

The team first showed that a hormone called atrial natriuretic peptide (ANP) helped the heart to regenerate in newborn mice, but not in adult mice. After a heart attack, cells around the damaged site increased production of a precursor of ANP called pro-ANP. Newborn mouse hearts produced much more ANP after injury than adult mouse hearts.

The research team aimed to turn muscle cells into factories for a precursor of ANP called pro-ANP. To do so, they created a therapy using the gene for pro-ANP, along with an element that allows the RNA to copy itself. They then packaged this self-amplifying RNA (saRNA) into microscopic packages called lipid nanoparticles (LNPs).

Injecting the saRNA-LNPs into the muscles of mice boosted production of pro-ANP in the treated muscle tissue. Some pro-ANP production was also seen in lymph nodes, but not in other organs. This lasted for at least four weeks. The pro-ANP produced in muscles moved into the blood and traveled to the heart, where it was converted into ANP.

The researchers next tested a single injection of saRNA-LNPs immediately after a heart attack in a mouse model. Treated mice had significantly improved heart function 28 days later compared to untreated mice. They also had less dead heart tissue and reduced scarring. Giving the treatment a week after the heart attack had similar beneficial effects but wasn’t as effective as immediate treatment.

The treatment provided similar benefits after heart attack in other animal models. These included aged mice, mice with atherosclerosis, mouse models of type 2 diabetes, and pig models.

The use of saRNA was key to the treatment’s effectiveness. Treatment with conventional RNA encoding pro-ANP that could not copy itself did not reduce the damaging effects of a heart attack. Importantly, the treatment did not cause any signs of systemic toxicity or abnormal changes to major organs. The only immune reaction to the treatment was some passing local inflammation.

These results point to saRNA as a promising treatment strategy to repair heart muscle damaged by a heart attack.

“Cell damage is a problem that not only affects the heart but many organs,” explains co-author Dr. Torsten Vahl of Columbia’s Irving Medical Center. “If we can prove that this type of therapy can regenerate cardiac cells in the clinical setting, the idea could potentially be transferred to other organs.”

—by Brandon Levy 

Related Links

• How sleep leads to healing after heart attack
• Delivering RNA therapies to brain tumors
• Stopping scar tissue improves healing after heart attack in mice
• Injected liquid forms a gel in damaged heart

References

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, Li Y, Lu C, Shen M, Lewis A, Huang K, Cheng K. Science. 2026 Mar 5;391(6789):edau9394. doi: 10.1126/science.adu9394. Epub 2026 Mar 5. PMID: 41785353.

Funding

NIH’s National Heart, Lung, and Blood Institute (NHLBI) and National Cancer Institute (NCI); American Heart Association; Columbia University Medical Center Cancer Center.