近日，
在这项研究中，课题组研究人员开发了一种细胞内saRNA-脂质纳米颗粒（saNppa-LNP）疗法，编码A型利钠肽（Nppa），用于心脏保护。单次注射诱导心房钠素前肽（pro-ANP）分泌维持4周；原ANP随后被心肌蛋白酶corin裂解为活性ANP，在母鼠和猪心肌梗死模型中产生明显的心脏保护作用。在相同剂量下，saNppa比常规mRNA具有更大的功效。单核转录组学鉴定出利钠肽受体1阳性（Npr1+）内皮细胞和心外膜细胞是主要的效应因子，sanpa - lnps重塑其旁分泌谱，促进心肌细胞再生和抑制纤维化。纵向生物安全评估显示无全身毒性。总之，这些结果表明，一次性saNppa-LNP治疗提供持久的心脏保护，支持基于saRNA-LNP的心脏治疗方法的更广泛潜力。
研究人员表示，自我扩增的RNA （saRNA）能够从单次给药中维持蛋白表达。
附：英文原文
Title: Single intramuscular injection of self-amplifying RNA of Nppa to treat myocardial infarction
Author: Kaiyue Zhang, Hongyan Tao, Dashuai Zhu, Zhang Yue, Shiqi Hu, Yiping Wu, Na Yan, Yilan Hu, Shuo Liu, Mengrui Liu, Torsten Peter Vahl, Lauren Sharan Ranard, Xiao Cheng, Alexander Romanov, Jiaming Liu, Savannah Weihang Zhang, Yuan Li, Chao Lu, Ming Shen, Andrew Lewis, Ke Huang, Ke Cheng
Issue&Volume: 2026-03-05
Abstract: 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: adu9394
Source: https://www.science.org/doi/10.1126/science.adu9394