The development of therapeutic agents to treat acute viral infections has historically resulted in a limited number of treatments progressing into the clinic. RNAi can be used to block expression of specific genes, which is highly advantageous for the treatment of viral infections.
To investigate the effectiveness of RNAi in the treatment of respiratory viral infections we designed siRNAs targeting highly conserved regions of Hendra virus (HeV) and Respiratory Syncytial virus (RSV). We have characterised their silencing efficiency in vitro via qRT-PCR, plaque assay, Western blotting and immunofluorescence microscopy. From these experiments we have identified siRNA sequences that displayed potent gene silencing of <95% as indicated by significant reductions in virus titre, RNA and protein.
A major barrier to the adoption of siRNA therapy is efficient delivery. Our laboratory has developed and tested a number of nanoparticle systems for in vivo siRNA delivery. Here, we have characterised our stealth liposomal vector for its ability to deliver siRNA to viral target cells in the lung upon intravenous injection. We show that greater than 60% of endothelial and 45% of epithelial cells were positive for siRNA liposome delivery in the lung.
We are currently testing our liposomal RNAi vector system to determine the ability of our HeV and RSV targeting siRNAs to reduce viral burden in the pulmonary system. The novel combination of intravenous delivery to the lung and RNAi technology potentially offers a superior means to treat acute respiratory viral infection.