Delivery of RNAi Therapeutics to the Airways—From Bench to Bedside

Qiu, Yingshan; Lam, Jenny K. W.; Leung, Susan W. S.; Liang, Wanling

The first animal study applying RNAi against influenza was reported by Ge et al. [145] . siRNA targeting NP or PA were complexed with PEI. The complexes were injected intravenously to the mice 3 h before or 5 h after influenza virus (PR8 H1N1) infection. The antiviral effect of siRNA targeting NP was dose-dependent and combination of siRNAs targeting NP and PA enhanced the effect. In the same study, shRNA targeting NP or PB was also investigated. The DNA was mixed with Infasurf, a commercial available pulmonary surfactant. After intranasal instillation, a significant reduction of virus titer was detected 24 h after infection although the effect was less prominent compared with intravenous injection of PEI complexes. Infasurf may play a role as nucleic acid carrier. Little is known about the interaction between DNA and pulmonary surfactant in the airspace. It could be possible that the DNA interacted with the charged lipid components in the pulmonary surfactant leading to the efficient spread and absorption in the airways [146] .