Design and development of effective siRNA delivery vehicles

As medicines become increasingly complex, their delivery becomes more challenging. To function, medicines must effectively navigate the body and reach their site of action. When the impediments to their delivery become too great, drug delivery vehicles are used. Small interfering RNA (siRNA) is a complex class of medicine. These duplex nucleic acid structures enter the RNA-interference pathway (RNAi) to alter the expression of a specific protein. The obstacles to siRNA delivery as a therapeutic agent are many. The work presented in PNAS by Dong et al. (1) represents an innovative approach toward the design and development of effective siRNA delivery vehicles. The goal of siRNA-based therapy is to knock down the expression of a specific protein to bring about a specific therapeutic effect. A number of siRNA therapeutics are in clinical trials (2). To exert their function, siRNA sequences must enter the RNAi pathway, which takes place in the cytosol. Two significant obstacles to the use of therapeutic siRNA are their macromolecular and polyanionic composition, which restrict their passive diffusion across the cell membrane into the cytosol. Therefore, to function siRNA therapeutics must be …