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

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

Respiratory infection can be caused by a wide range of microorganisms in the airways including bacteria and viruses [120] . It is one of the most common reasons for hospitalization among adults [121] . Due to the rise of antimicrobial resistance, many infectious diseases including respiratory infections have become difficult to treat. RNAi therapeutics appears to be an attractive approach to fight against infections [122] . The pre-clinical studies of RNAi therapeutics to combat against respiratory infections are summarized in Table 3 . Since RNAi was first reported to inhibit respiratory syncytial virus (RSV) in 2001 [131] , an increasing number of studies have been initiated to explore the potential of RNAi technology to treat other respiratory viral infections including influenza [86, 127, 132, 133] and severe acute respiratory syndrome (SARS) [134] . RNAi molecules offer several advantages as antiviral therapeutics. They can specifically target the conserved region of mRNA sequence in the viral genome, making it effective against mutated viral strains. In addition, RNAi molecules can be designed rapidly to target viral genes, shortening the lead time of developing new antiviral agents, which is particularly useful in response to an infection outbreak. To achieve effective antiviral effect, the viral targets must be essential for the pathogenesis of viral infection and/or replication cycle. It is also desirable that the target genes share similar conserved sequence among different strains to achieve broad viral inhibition. Furthermore, the viral gene should be substantially different with human gene to minimize any undesirable side effects.