A new RNA-based therapy shows promise in supporting the heart’s regenerative capacity after a myocardial infarction, providing a minimally invasive option for cardiac repair.
This approach, developed by a team led by Columbia Engineering’s Ke Cheng, involves a single injection into skeletal muscle, which then generates a targeted therapy that activates within the heart.
It could revolutionise current treatments, decreasing dependence on invasive procedures such as surgeries or transplants.
Present interventions for heart attack patients mainly aim to restore blood flow through stenting or bypass surgery.
However, damaged muscle tissue remains irreplaceable, often leading to heart failure over time. The new RNA therapy aims to bridge this gap by stimulating myocardial regeneration, utilising the body’s own mechanisms.
Cheng, the Alan L Kaganov Professor of Biomedical Engineering, explained that the therapy uses specially designed RNA-lipid nanoparticles that encode the Nppa gene, which produces the precursor to atrial natriuretic peptide (ANP).
After injection into the arm, these particles cause muscle cells in the thigh or arm to produce pro-ANP, a non-reactive circulating molecule.
The enzyme Corin, which is abundant in cardiac tissue, then converts pro-ANP into active ANP locally within the heart.
This targeted activation allows for a drug delivery method that bypasses the heart’s lack of natural accumulation mechanisms and avoids the invasiveness of traditional approaches such as intracardiac injections or pericardial infusions.
By deploying the therapy peripherally, surgeons could administer treatment with a simple injection, reducing procedural risks and patient recovery time.
Preclinical studies in small and large animal models demonstrated that a single injection significantly reduced scar formation and improved cardiac function.
The therapy’s design uses self-amplifying RNA (saRNA) that replicates within cells, prolonging pro-ANP production for at least four weeks from a single dose.
This sustained effect highlights its potential to support continuous repair processes.
This method also offers potential cost and accessibility benefits compared with existing treatments, such as stem cell transplants or organ regeneration, which are often resource-intensive and invasive.
