In Vivo Delivery of RNAi by Reducible Interfering Nanoparticles (iNOPs)
Department of Biochemistry and Molecular Pharmacology
Biochemistry | Medicinal and Pharmaceutical Chemistry | Medicinal-Pharmaceutical Chemistry | Molecular Genetics
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 approximately 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.
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Citation: Baigude H, Su J, McCarroll J, Rana TM. In Vivo Delivery of RNAi by Reducible Interfering Nanoparticles (iNOPs). ACS Med Chem Lett. 2013 Aug 8;4(8):720-723. Link to article on publisher's site
Nanoparticle, iNOP, reducible nanoparticles, siRNA delivery
Baigude, Huricha; Su, Jie; McCarroll, Joshua; and Rana, Tariq M., "In Vivo Delivery of RNAi by Reducible Interfering Nanoparticles (iNOPs)" (2013). University of Massachusetts Medical School Faculty Publications. 381.