Respiratory Syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness in infants and children worldwide, with annual total healthcare costs estimated to be up to $50 million in Australia. As well as producing an acute respiratory infection, there is growing evidence that severe or persistent RSV infection in infancy is associated with the development of childhood asthma and recurrent wheezing. Currently there are no antivirals that show a significant benefit in decreasing viral infection severity or duration, and this has been further complicated by limited direct intranasal delivery of compounds to the lung due to increased fluid production and tissue remodelling during infection.
We have developed a nanoparticle in vivo delivery system that is highly efficient at delivering small interfering RNA (siRNA) intravenously to lung epithelial cells, the target of RSV infection. Labelled nanoparticles were examined for their bio-distribution and ability to deliver to the lung in mice after tail vein injection. Following this, nanoparticles containing siRNA targeting the phosphoprotein (P) gene of RSV were administered either intranasally or intravenously to the mice after initial infection and examined for therapeutic efficacy during virus infection.
Here we show that we were able to efficiently deliver siRNA to the cells of the murine lung by intravenous liposomal administration and that siRNA against RSV resulted in targeted knockdown of RSV P gene expression observed in the lung. This correlated with a reduction in RSV virus levels and both of these effects were dramatically improved when the treatment was given intravenously.
Taken together, our approach overcomes the significant barriers seen with intranasal delivery of siRNA and classic antivirals during infection. This work demonstrates an attractive alternate therapeutic delivery strategy for the treatment of acute respiratory viral diseases and could be instrumental in further reducing development of chronic respiratory disease.