(645b) Development of pH-Responsive Nanogels for Delivery of siRNA

The landmark discovery of RNA-mediated interference (RNAi) in 1998 has sparked a massive research effort in biological science and redefined understanding of the mechanisms of gene regulation. RNAi pathways are guided by the presence of small interfering RNA (siRNA), short strands of duplex RNA capable of selective, potent, and reversible silencing of target genes. Owing to its remarkable potency and low therapeutic dosage, siRNA holds extraordinary promise as a new biological therapeutic. However, efficient delivery has been implicated as the major hurdle to its widespread clinical application. We have developed a series of pH-responsive nanoscale hydrogels for delivery of siRNA. Nanogels were synthesized using a facile photoemulsion polymerization with an average particle size near 50 nm and displayed reversible, pH-dependant swelling near pH 6.9. Effects of copolymer composition, nanogel core hydrophobicity, and cross-linking ratio have been investigated. Our results suggest these pH-responsive nanogels can be used to mediate endosomal rupture and enhance intracellular delivery of siRNA in the gastrointestinal tract.