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A single injection induced sustained pro\u2013atrial 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\u2013positive (\n                    <jats:italic toggle=\"yes\">Npr1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    ) 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\u2013based approaches for cardiac therapy.\n                  <\/jats:p>","DOI":"10.1126\/science.adu9394","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T19:01:12Z","timestamp":1772737272000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":26,"title":["Single intramuscular injection of self-amplifying RNA of\n                    <i>Nppa<\/i>\n                    to treat myocardial infarction"],"prefix":"10.1126","volume":"391","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9906-9053","authenticated-orcid":true,"given":"Kaiyue","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Columbia University, New York, NY, 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