信使核糖核酸
全身给药
载脂蛋白B
核糖核酸
化学
医学
分子生物学
生物
体内
生物化学
基因
胆固醇
生物技术
作者
Hamideh Parhiz,Vladimir V. Shuvaev,Norbert Pardi,Makan Khoshnejad,Raisa Y. Kiseleva,Jacob S. Brenner,Thomas Uhler,Steven Tuyishime,Barbara L. Mui,Ying K. Tam,Thomas D. Madden,Michael J. Hope,Drew Weissman,Vladimir R. Muzykantov
标识
DOI:10.1016/j.jconrel.2018.10.015
摘要
Systemic administration of lipid nanoparticle (LNP)-encapsulated messenger RNA (mRNA) leads predominantly to hepatic uptake and expression. Here, we conjugated nucleoside-modified mRNA-LNPs with antibodies (Abs) specific to vascular cell adhesion molecule, PECAM-1. Systemic (intravenous) administration of Ab/LNP-mRNAs resulted in profound inhibition of hepatic uptake concomitantly with ~200-fold and 25-fold elevation of mRNA delivery and protein expression in the lungs compared to non-targeted counterparts. Unlike hepatic delivery of LNP-mRNA, Ab/LNP-mRNA is independent of apolipoprotein E. Vascular re-targeting of mRNA represents a promising, powerful, and unique approach for novel experimental and clinical interventions in organs of interest other than liver.
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