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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.

SUBMITTER: Baigude H

PROVIDER: S-EPMC3850243 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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In Vivo Delivery of RNAi by Reducible Interfering Nanoparticles (iNOPs).

Baigude Huricha H Su Jie J McCarroll Joshua J Rana Tariq M TM

ACS medicinal chemistry letters 20130618 8

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 c ...[more]

PMID: 24319542

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