Use of synthetic nucleic acids to manipulate gene function has become a powerful tool for both basic research and therapeutics. Silencing disease targets by RNA interference is a promising approach to drug development, and various experimental RNA therapies are currently in clinical development by both small and large biotechnology companies. miRNAs are also being developed for disease treatment and diagnosis. However, lack of specifically targeted, efficient and safe vehicles for systemic delivery of small RNA payloads in vivo is a serious challenge. Synthetic nucleic acids face a number of physiological barriers in the bloodstream, and their intracellular uptake is hampered by the fact that they are highly charged and have much larger molecular wieght than small-molecule drugs. Current strategies to circumvent these problems includes local administration, chemical modifications of nucleic acids, viral delivery vectors, lipid-based delivery systems, polymer-based delivery systems and nanoparticle encapsulation. These methods have serious flaws including toxicity, inummue effects, non-selectively and high cost of manufacturing. Therefore, novel ways to deliver synthetic nucleic acids for use in humans and experimental animal models are sorely needed.