A single intramuscular saNppa-LNP injection induced 4 weeks of cardioprotective pro-ANP secretion, outperforming conventional mRNA and promoting cardiomyocyte regeneration without toxicity.
Does a single intramuscular injection of saNppa-LNP improve cardioprotection compared to conventional mRNA in mouse and swine myocardial infarction models?
A single intramuscular injection of saNppa-LNP provides durable cardioprotection and outperforms conventional mRNA in preclinical myocardial infarction models, highlighting the potential of saRNA-LNP therapies.
Absolute Event Rate: 0% vs 0%
Self-amplifying RNA (saRNA) enables sustained protein expression from a single administration. In this study, we developed an intramuscular saRNA-lipid nanoparticle (saNppa-LNP) therapy encoding natriuretic peptide type A ( Nppa ) for cardioprotection. A single injection induced sustained pro–atrial natriuretic peptide (pro-ANP) secretion for 4 weeks; pro-ANP was subsequently cleaved by the cardiac protease corin into active ANP, producing robust cardioprotection in mouse and swine myocardial infarction models. At equivalent doses, saNppa achieved greater efficacy than conventional mRNA. Single-nucleus transcriptomics identified natriuretic peptide receptor 1–positive ( Npr1 + ) endothelial and epicardial cells as primary effectors, with saNppa-LNPs reshaping their paracrine profile to promote cardiomyocyte regeneration and suppress fibrosis. Longitudinal biosafety assessments revealed no systemic toxicity. Together, these results demonstrate that one-shot saNppa-LNP therapy offers durable cardioprotection, supporting the broader potential of saRNA-LNP–based approaches for cardiac therapy.
“In this study, a single intramuscular injection of self-amplifying RNA encoding pro–atrial natriuretic peptide reduced infarct size and improved cardiac function after myocardial infarction in mice and pigs.”
Key implication: If validated in humans, this could revolutionize post-MI treatment with a simple injection that enables self-repair, potentially reducing heart failure incidence and extending to other organ regeneration therapies.
This paper garnered significant attention on X with 388 likes and 72 reposts in the past 14 days, discussed among cardiology professionals for its innovative approach to heart repair. It has been shared widely in academic circles with early downloads exceeding 10,000 on the journal site.
Key implication: If validated in humans, this could revolutionize post-MI treatment with a simple injection that enables self-repair, potentially reducing heart failure incidence and extending to other organ regeneration therapies.
Zhang et al. (Thu,) reported a other. A single intramuscular saNppa-LNP injection induced 4 weeks of cardioprotective pro-ANP secretion, outperforming conventional mRNA and promoting cardiomyocyte regeneration without toxicity.