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.
Nanoparticle, iNOP, reducible nanoparticles, siRNA delivery
DOI of Published Version
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
ACS medicinal chemistry letters
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.