RNA-Based Therapies Show Promise for Heart Repair and Cardiovascular Disease Prediction

Researchers have developed an RNA therapy that enhances the heart's ability to repair itself after injury through a single injection into the arm, according to a study published March 5 in Science. In lab experiments, the treatment significantly reduced scarring and improved heart function in small and large animals.

"The heart is one of the organs with the least ability to regenerate," said the Alan L. Kaganov Professor of Biomedical Engineering at Columbia Engineering. "The spontaneous regeneration power is very, very limited."

The therapy uses RNA-lipid nanoparticles that encode Nppa, causing muscle cells in the thigh or arm to produce a molecule called pro-ANP. This molecule circulates through the bloodstream until it reaches the heart, where a specific enzyme called Corin transforms it into atrial natriuretic peptide (ANP). Corin is roughly 60 times more common in the heart than in other organs.

During the first days of life, many mammals have a short-lived ability to regenerate heart muscle cells. ANP plays a key role by encouraging the growth of new blood vessels, calming inflammation, and reducing the formation of scars. As an individual ages, the amount of ANP in their bodies decreases substantially, and the regenerative capacity observed in newborn hearts largely disappears by adulthood.

The team observed this effect in experiments that compared newborn and adult mice after a heart attack. In newborn hearts, the gene that produces ANP's precursor ramped up more than 25 times its normal level. In adult hearts, it rose only about 10 times, which might be insufficient to support meaningful regeneration. When the team experimentally blocked that gene, called Nppa, in newborn mice, the hearts lost much of their ability to heal.

Researchers have understood the potential of ANP for decades, but it's difficult to use as a conventional drug because it begins breaking down after just a few minutes in the body. To keep production going long enough to help, the team used a specially designed self-amplifying RNA (saRNA) that replicates itself inside cells.

An attending physician at Columbia University Irving Medical Center/NewYork-Presbyterian Hospital and an assistant professor of medicine at Columbia's Vagelos College of Physicians and Surgeons sees an injection that can help the heart heal as an exciting step forward. "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. Too many times, they are left with severe heart damage that results later in heart failure."

Therapies based on RNA technology stand to be less expensive and more accessible than existing interventions, such as organ transplantation or stem cell therapies.

In separate research, tiny RNA molecules carried by extracellular vesicles in the bloodstream can accurately predict kidney function decline and cardiovascular risk in chronic kidney disease (CKD), as reported by researchers from Science Tokyo. The work was made available online on December 10, 2025, and published in Volume 15, Issue 1 of the Journal of the American Heart Association on January 06, 2026.

Chronic kidney disease affects more than 850 million people globally. While the condition is widely known for gradually impairing kidney function, many patients die prematurely from cardiovascular complications long before they ever require dialysis or transplantation.

Current tools used to monitor CKD rely heavily on biomarkers such as protein levels in urine (proteinuria) or glomerular filtration rate to assess kidney function, which share notable limitations. While these measurements reflect existing kidney damage, they do not capture the finer molecular changes that link kidney dysfunction to harm in other organs, such as the heart.

The research team focused on microRNAs (miRNAs) found in circulating extracellular vesicles (cEVs), which are nanoscale membrane-bound vesicles naturally released by cells. Once considered cellular debris, they are now recognized as carriers of biologically active molecules that enable communication between distant organs. Because these vesicles protect their molecular cargo from degradation, they provide a stable source of information about disease processes occurring throughout the body.

In an initial cohort of 36 patients, the researchers identified 23 miRNAs that were significantly depleted in cEVs in advanced CKD. Many of these miRNAs regulate pathways involved in vascular remodeling, inflammation, metabolic alterations, and cellular aging—processes that can drive both kidney damage and cardiovascular risks.

Using statistical modeling and machine learning, the team narrowed the results to three key miRNAs that most strongly predicted kidney decline and validated them in a cohort of 234 patients with CKD. They combined these new biomarkers with cystatin C and urinary protein-to-creatinine ratio measurements to develop an integrated risk model, which they called the 'M3V2 equation.'

As revealed by a long-term follow-up lasting several years, the new model significantly outperformed conventional clinical markers and existing risk classification tools in predicting both kidney decline and major cardiovascular events. Interestingly, it was effective regardless of the underlying cause of CKD or the presence of cardiovascular disease.

Emerging research also suggests reversible RNA editing mechanisms may influence heart disease biology while opening new avenues for biomarkers and next-generation cardiovascular therapies. In a recent mini-review published in the journal Communications Biology, researchers summarize emerging but still evolving evidence exploring potential links between dysregulated post-transcriptional RNA modifications and cardiovascular disease (CVD) risk.

Post-transcriptional RNA modification, specifically adenosine-to-inosine (A-to-I) editing, is a key regulatory mechanism that alters RNA structure and function without changing the underlying DNA sequence. Review findings suggest that RNA editing is not merely a byproduct of cellular activity but appears essential for normal development and cardiovascular homeostasis, noting emerging associations rather than definitive causal relationships between editing and several CVDs, including coronary artery disease (CAD), atherosclerosis, hypertension, and heart failure (HF).

The most prevalent form of RNA editing is A-to-I editing, in which ADAR enzymes convert adenosine nucleotides to inosine. Since the body's translation machinery reads inosine as guanosine, a single edit can in some cases alter RNA stability, splicing, or protein function.

Research aimed at identifying the physiological cardiovascular-specific function of post-transcriptional RNA modifications has revealed that, in the heart and blood vessels, this process may contribute to maintaining cellular balance and immune tolerance rather than acting solely as a protective mechanism. RNA editing has been reported to help prevent inappropriate activation of the innate immune system against the body's own double-stranded RNA.

Mice completely lacking the Adar1 gene ubiquitously die by embryonic day 10.5 due to widespread cell death in the heart and other tissues. When Adar1 is deleted only in cardiomyocytes (heart muscle cells), embryos exhibit severe developmental abnormalities, potentially due to reduced cell proliferation and increased apoptosis (programmed cell death).