The promise of small interfering RNAs siRNAs and their ability to knock-down or attenuate diseased genes has yet to be realized - as demonstrated by their absence in mainstream pharmaceutical applications. A key hurdle to widespread adoption and use of RNA interference is the lack of drug delivery carriers that deliver RNAi inducing molecules, including plasmid DNA and siRNAs systemically and efficiently. Customers investigating the use of Ac-DEX for therapeutic delivery of nucleic acids recognize the following: biocompatibility of Ac-DEX; protection afforded to genetic cargoes as it traverses to the site of therapeutic delivery; efficient cellular uptake; limited opsonization by the reticuloendothelial system (RES); avoidance of rapid elimination via the kidney; and efficient release of negatively charged genetic cargoes.
Currently, a wide variety of carriers have been explored to address siRNA delivery challenges. These include lipids, viral vectors, and polymers. However, each strategy comes with advantages and limitations. For example, viral vectors are efficient in transfection, but introduce numerous safety concerns including immune activation and oncogenesis. As result, lipid-based and polymer-based delivery systems have emerged as leading candidates for delivery of siRNA. Polysaccharides, for instance, offer low toxicity, are biodegradeable, and minimally activate the immue system. However, many delivery systems, including those based on chitosan have been tested and none have emerged for routine delivery in clinical siRNA applications. As a result, a formulation of a carrier based on Ac-DEX for the delivery of siRNA has already been demonstrated and continues to be under evaluation in several therapeutic areas. It is anticipated that Ac-DEX will form the basis of novel siRNA therapeutic delivery strategies in the near future.