title: In Vivo Delivery of RNAi by Reducible Interfering Nanoparticles (iNOPs).
abstract: RNA interference (RNAi) has considerable potential as a therapeutic strategy, but the development of efficient in vivo RNA delivery methods remains challenging. To this end, we designed and synthesized chemically modified interfering nanoparticles (iNOPs) composed of functionalized poly-l-lysine dendrimers modified with reducible spacers to facilitate release of small interfering RNAs (siRNAs) in vivo. We show that the novel siRNA-iNOP complexes mediate efficient gene-specific RNAi in cultured cells and in mice, where they display enhanced tissue-targeting capabilities. At a clinically feasible dose of 1 mg kg-1, apolipoprotein B (apoB) siRNA-iNOP complexes achieved ∼40-45% reduction of liver apoB mRNA and plasma apoB protein levels within 48 h of administration to mice, without apparent toxicity. Collectively, these findings demonstrate that siRNA delivery by the modified reducible iNOPs can provide a clinically significant and potentially tissue-specific new approach for RNAi therapy.
authors: Program for RNA Biology, Sanford-Burnham Medical Research Institute , 10901 North Torrey Pines Road, La Jolla, California 92037, United States ; Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School , Worcester, Massachusetts 01605, United States.
authors: Huricha
authors: H
authors: Baigude
authors: Jie
authors: J
authors: Su
authors: Joshua
authors: J
authors: McCarroll
authors: Tariq M
authors: TM
authors: Rana
keywords: Nanoparticle; iNOP; reducible nanoparticles; siRNA delivery