Prospects of RNA interference therapy in respiratory viral diseases: update 2006

Respiratory viruses, such as influenza, parainfluenza and respiratory syncytial virus (RSV), claim millions of lives annually. At present, there is no completely effective vaccine or drug against these highly mutable RNA viruses. Passive antibody therapies for RSV, despite their limited application and staggering cost, enjoy a virtual monopoly in a multibillion-dollar global market. Recently, however, pioneering discoveries have launched RNA interference as a novel, nucleic acid-based therapy against viral pathogens. Specifically, small interfering RNAs (siRNAs) offered protection against respiratory syncytial virus, parainfluenza and influenza. siRNA against RSV has entered Phase I clinical trials in humans, and preliminary reports are promising. if appropriately formulated for improved specificity, delivery and pharmacokinetics, siRNAs may indeed become effective antivirals in the clinics of the future. This paper provides an overview of the prospects and hurdles facing the antiviral siRNA drugs, with special emphasis on RSV.