Single intramuscular injection of self-amplifying RNA of Nppa to treat myocardial infarction

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…

• AH
  American Heart Association

  Awards: 26PRE1566968, P30CA013696, 19EIA34660286
• NI
  National Institutes of Health

  Awards: HL146153, HL144002, P30CA013696, HL140562, HL164998, HL179818, HL170612, HL154154, HL175373
• NC
  National Cancer Institute

  Award: P30CA013696