Abstract：
Among various mRNA carrier systems, lipid nanoparticles (LNPs) stand out as the most clinically advanced. While current clinical trials of mRNA/LNP therapeutics mainly address liver diseases, the potential of mRNA therapy extends far beyond─yet to be unraveled. To fully unlock the promises of mRNA therapy, there is an urgent need to develop safe and effective LNP systems that can target extrahepatic organs. Here, we report on the development of sulfonium lipid nanoparticles (sLNPs) for systemic mRNA delivery to the lungs. sLNP effectively and specifically delivered mRNA to the lungs following intravenous administration in mice. No evidence of lung and systemic inflammation or toxicity in major organs was induced by sLNP. Our findings demonstrated that the newly developed lung-specific sLNP platform is both safe and efficacious. It holds great promise for advancing the development of new mRNA-based therapies for the treatment of lung-associated diseases and conditions.
摘要：
在各种mRNA载体系统中，脂质纳米颗粒（LNPs）是临床上最先进的。虽然目前mRNA/LNP疗法的临床试验主要针对肝脏疾病，mRNA治疗的潜力远远超出了──尚未被揭示。为了完全解开mRNA治疗的希望，迫切需要开发能够靶向肝外器官的安全有效的LNP系统。这里,我们报道了用于全身mRNA递送到肺的锍脂质纳米颗粒（sLNP）的开发。在小鼠中静脉内施用后,sLNP有效且特异性地将mRNA递送至肺。sLNP在主要器官中没有诱导肺部和全身性炎症或毒性的证据。我们的发现表明，新开发的肺特异性sLNP平台既安全又有效。它为推进新的基于mRNA的治疗肺部相关疾病和病症的疗法的开发提供了巨大的希望。
