(484e) Needle-Shaped Polymer Particles for siRNA Delivery

RNA interference is a ubiquitous method of gene regulation where a double stranded RNA can be utilized to knockdown gene expression in a sequence dependent manner. RNAi therapy can be used to suppress virtually any gene from cellular oncogenes to viral genes which can be a potential cure for diseases that do not fall under the realm of the current small molecule based therapies. Delivery of therapeutic RNAs such as siRNA is extremely challenging due to the high negative charge, high molecular weight, high enzymatic degradation and intracelullar site of delivery. Numerous carriers in the form of liposome based carriers, peptide based carriers, polymeric complexations, polymer encapsulations and various nanoparticulate carriers have been developed for siRNA delivery. In spite of these advances, endosomal escape without causing cellular toxicity remains an obstacle for most carriers. A carrier, which could escape the endosome or deliver siRNA directly into the cytoplasm without causing high toxicity would serve as an idea siRNA delivery vehicle. Here, we show that needle-shaped polymeric particles cause transient cell membrane permeability increasing cytoplasmic delivery of siRNA. We prepare needle-shaped polystyrene particles by the film stretching process. These particles were incubated with cells along with siRNA. The needle shaped particles caused significant knockdown of green fluorescent protein in endothelial cells. The physical method of siRNA delivery described here holds great therapeutic potential since it reduces the toxic effects caused by current carriers while retaining the versatility of polymeric carriers that can be used to target a specific diseased site.