Single intramuscular injection of self-amplifying RNA of Nppa to treat myocardial infarction - PubMed
2 hours ago
- #Myocardial Infarction
- #saRNA
- #Cardioprotection
- Self-amplifying RNA (saRNA) enables sustained protein expression from a single administration.
- Intramuscular saRNA-lipid nanoparticle (saNppa-LNP) therapy encoding natriuretic peptide type A (Nppa) was developed for cardioprotection.
- A single injection induced sustained pro-atrial natriuretic peptide (pro-ANP) secretion for 4 weeks.
- Pro-ANP was cleaved by cardiac protease corin into active ANP, providing robust cardioprotection in mouse and swine myocardial infarction models.
- saNppa achieved greater efficacy than conventional mRNA at equivalent doses.
- Single-nucleus transcriptomics identified Npr1+ endothelial and epicardial cells as primary effectors.
- saNppa-LNPs reshaped the paracrine profile of these cells to promote cardiomyocyte regeneration and suppress fibrosis.
- Longitudinal biosafety assessments revealed no systemic toxicity.
- One-shot saNppa-LNP therapy offers durable cardioprotection, supporting the potential of saRNA-LNP-based approaches for cardiac therapy.