Development of targeted delivery systems for nucleic acid drugs.

Our increased understanding of disease pathogenesis is the basis for developing novel nucleic acid drugs. The main challenge encountered in this development is how to maintain therapeutically meaningful concentrations of the drugs in the vicinity of their targets for the desired periods. The intrinsic difficulty arises from the fact that nucleic acid drugs are not readily transported across membranes. Hence, their delivery and transport characteristics at the whole body, organ and cellular levels need to be thoroughly examined. Liposomes and receptor-mediated polycation systems are promising carriers for their delivery in vivo. There are many barriers to be overcome for successful antisense and gene therapies. Along with other factors, disposition, stability against nucleases, binding to cell surface receptor and internalization, and intracellular trafficking affect the in vivo delivery and efficacy of nucleic acid drugs. This review article discusses the delivery and transport of these compounds.