A new study published in Science describes a therapy that could help the heart repair itself after injury, researchers announced on March 13. The approach uses RNA technology to boost the heart’s natural healing abilities and may offer a less invasive alternative to current treatments.
The research addresses a significant challenge in cardiology: while doctors can restore blood flow after a heart attack, the damaged muscle cells are not naturally replaced. "The heart is one of the organs with the least ability to regenerate," said Ke Cheng, Alan L. Kaganov Professor of Biomedical Engineering at Columbia Engineering. "The spontaneous regeneration power is very, very limited."
Cheng and his colleagues developed an injectable RNA-lipid nanoparticle therapy that prompts skeletal muscle cells to produce pro-ANP, a precursor molecule that circulates through the bloodstream until it reaches the heart. There, an enzyme called Corin—much more common in cardiac tissue than elsewhere—converts pro-ANP into atrial natriuretic peptide (ANP), which supports blood vessel growth and reduces scarring. "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 to inject the particles into the arm."
Torsten Vahl, co-author and attending physician at Columbia University Irving Medical Center/NewYork-Presbyterian Hospital, highlighted how this method could address unmet needs for patients who suffer lasting damage after heart attacks. "As a clinician who opens up arteries with stents for patients who come to us with heart attacks, I am highly aware that we have a large unmet need for our patients," Vahl said. "Too many times, they are left with severe heart damage that results later in heart failure."
Laboratory experiments showed that a single injection reduced scarring and improved function in both small and large animals—even when treatment was delayed or tested in animals with other health conditions such as diabetes or genetic predispositions to cardiovascular disease. The self-amplifying RNA used in this therapy allows its effects to last at least four weeks from one dose.
Cheng explained that their strategy was inspired by how newborn mammals can briefly regenerate cardiac tissue due to higher levels of ANP—a capacity lost as individuals age because ANP production declines sharply over time.
Delivering drugs directly to the heart has traditionally required invasive procedures performed in specialized labs; however, this new approach avoids those challenges by using systemic delivery and organ-specific activation mechanisms.
Looking ahead, Cheng hopes to manufacture this therapy at Columbia Initiative in Cell Engineering and Therapy and begin phase-one safety trials at Columbia University Irving Medical Center. "We can leverage our in-house resources for manufacturing and then start a clinical trial," Cheng said. "Columbia can do both."
