Single intramuscular injection of self-amplifying RNA of Nppa to treat myocardial infarction
Summary
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 myocardia
Content
# Single intramuscular injection of self-amplifying RNA of Nppa to treat myocardial infarction
*Published: 2026 Mar 5*
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.
DOI: 10.1126/science.adu9394