A novel mRNA-based therapy has induced cardiac regeneration in a mouse heart attack model.
Researchers from the Lewis Katz School of Medicine at Temple University (PA, USA) have unveiled an innovative therapy that uses modified messenger RNA (modRNA) technology to reactivate a dormant developmental gene, potentially enabling the heart to repair itself after damage.
Heart attacks continue to be among the deadliest and most debilitating health conditions across the globe. What makes them particularly devastating is that when the heart is deprived of oxygen during an attack, specialized muscle cells called cardiomyocytes die off permanently. Unlike many other body tissues, the heart has virtually no capacity to regenerate lost cells, and current treatments only manage the symptoms of heart damage rather than repairing or replacing the damaged tissue.
However, in the current study, the researchers demonstrated that delivering a gene called PSAT1 directly to damaged heart tissue in mice could stimulate regeneration and significantly improve cardiac function following a heart attack.
Corresponding author Raj Kishore explained: “PSAT1 is a gene that is highly expressed during early development but becomes virtually silent in the adult heart. We wanted to explore whether reactivating this gene in adult heart tissue could promote regeneration after injury.”
Bioprinting shape-morphing hearts
A novel bioprinting technique has been developed to create tissues that reshape themselves in response to forces generated by cells, mimicking the natural processes that occur during organ development.
To investigate this, the team utilized modRNA to deliver PSAT1 into the heart tissue of mice immediately after a heart attack. They observed an increase in cardiomyocyte proliferation and blood vessel formation along with reduced tissue scarring. This resulted in significantly enhanced heart function and survival compared to untreated mice.
The therapy was demonstrated to work by activating the serine synthesis pathway, a metabolic network that supports cell division and stress resistance. This activation creates conditions that allow heart muscle cells to survive, multiply and form new functional tissue rather than scars.
Utilizing modRNA technology has a number of benefits. It enables the delivery of genes like PSAT1 with high specificity and limited side effects and, unlike viral gene therapies, modRNA does not integrate into the genome, reducing the potential for long-term risks.
While the research is still in preclinical stages, the team is optimistic about its potential. They plan to advance testing in larger animal models and optimize delivery methods before moving toward potential human trials.