Nanoscale “DNA Baskets” for the Delivery of siRNA

Abstract

Silencing of gene expression by small interfering RNA (siRNA) is promising for drug target discovery and as a therapy. However, a major impediment to the practical use of this technology is an inherent instability of siRNA in the bloodstream, partly due to susceptibility to nucleases. To address this restriction, we evaluated a novel DNA/albumin-based siRNA delivery vehicle that forms a “basket” surrounding the siRNA and provides both steric separation of siRNA from nucleases and local excess of the substrate for nuclease action; thus, slowing the rate of the degradation of siRNA. We found that variation of the albumin concentration in basket construction can significantly decrease the mean size of the basket. Smaller siRNA-containing DNA baskets may increase cellular uptake. We found that the degradation of siRNA is delayed when siRNA is prepared with this delivery vehicle, implying that DNA baskets are a promising technology for further development as the delivery vehicle for siRNA therapeutics.