Delivery to Macrophages and Efficacy of Orally Administered RNAi Compounds (42.27)

Abstract

Data will be presented on a method for RNAi compound delivery utilizing RNA encapsulated in beta-glucan shells. When orally administered to mice, these encapsulated nucleic acids traverse the intestinal epithelia by an M cell transcytosis mechanism and are then endocytosed by macrophages. Macrophages containing RNAi compounds migrate to sites of inflammation, and the targeted RNA is specifically inhibited by RNA interference. This formulation presents some unique advantages for therapeutic RNAi including oral mode of administration, low dose (ug/kg/day) and specific delivery to immune cells possibly affording safety advantages for some targets. This novel mode of RNA administration can be used to down-regulate target genes involved in multiple inflammatory disease indications.