Systemic delivery of biotherapeutic RNA to the myocardium transiently modulates cardiac contractility in vivo.

ABSTRACT: Lipid nanoparticles (LNP) represent a versatile platform for improving delivery of therapeutic nucleic acids. Yet, delivery to the myocardium remains a formidable challenge due to local barriers in the heart and systemic hindrances. In particular, plasma apolipoprotein E (apoE) directs LNP to the liver, limiting potential extrahepatic delivery. Here, we report a cardiotropic LNP (cLNP), which within 30 min post-intravenous injection accumulates in the heart of ApoE knockout (Apoe^-/-) mice. The findings were confirmed for Apoe^-/- rats and for wild-type mice after siRNA-mediated plasma apoE ablation. To test cardiac-specific functional effects as a proof of concept, we used cLNP loaded with siRNA to ATP2A2, encoding the sarcoplasmic-endoplasmic reti

SUBMITTER: Shuvaev VV 

PROVIDER: S-EPMC12304964 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature