Researchers at Columbia University have developed an innovative RNA-based therapy that may help the heart repair itself after injury, potentially transforming the way heart attacks are treated. The study, published in the journal Science on March 5, demonstrates a minimally invasive treatment that encourages the body to produce its own healing molecules.
The therapy was designed by researchers led by Cheng and tested in collaboration with clinicians at Columbia University Irving Medical Center and NewYork-Presbyterian Hospital. Instead of delivering medicine directly to the heart through invasive procedures, the treatment can be administered as a simple injection in the arm.
“You don’t have to open the chest or send a wire to the heart to deliver this drug,” Cheng said. “In principle, all the clinician needs to do is inject the particles into the arm.”
The research focuses on a natural hormone called Atrial Natriuretic Peptide (ANP), which helps newborn hearts regenerate by encouraging new blood vessel growth, reducing inflammation, and limiting scar formation. However, levels of this hormone decrease significantly with age, which limits the heart’s ability to repair itself after a heart attack.
To overcome this challenge, the research team created RNA-lipid nanoparticles that deliver genetic instructions encoding the gene NPPA into skeletal muscle cells. These cells then produce an inactive precursor molecule called pro-ANP, which circulates in the bloodstream until it reaches the heart. There, an enzyme known as Corin—present at much higher levels in heart tissue—converts it into active ANP, triggering healing processes.
In laboratory experiments involving both small and large animals, a single injection significantly reduced scarring and improved heart function after a heart attack. The therapy uses self-amplifying RNA (saRNA), allowing the treatment to remain active for at least four weeks after a single dose.
Torsten Vahl, an attending physician at Columbia University Irving Medical Center and assistant professor of medicine at Vagelos College of Physicians and Surgeons, emphasized the potential clinical impact.
“As a clinician who opens arteries with stents for patients who come to us with heart attacks, I am highly aware that we have a large unmet need,” Vahl said. “Too many times, patients are left with severe heart damage that later results in heart failure.”
Unlike current treatments such as organ transplants or stem cell therapies, RNA-based treatments may eventually be more affordable and accessible. The research team also tested the therapy in aged animals, animals with diet-induced Type 2 Diabetes, and models prone to Atherosclerosis. The treatment remained effective even when administered a week after a heart attack.
Beyond heart repair, the researchers believe the same RNA-delivery approach could be applied to other conditions, including Kidney Disease, High Blood Pressure, and Preeclampsia.
The team plans to manufacture the therapy through the Columbia Initiative in Cell Engineering and Therapy and hopes to begin a Phase I clinical safety trial at Columbia University Irving Medical Center in the future.
“If we can prove this therapy works in humans, it could open the door to regenerative treatments not only for the heart but for other organs as well,” the researchers noted.
