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

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

The approach of RNAi-based therapeutics against TB aims to modulate the gene expression of the host instead of the bacillus because bacteria do not contain the requisite machinery for RNAi. Currently, RNAi has been investigated for TB treatment in two directions: (i) targeting the host factors that are essential for the survival of mycobacteria; and (ii) modulating the host immune response to facilitate the elimination of mycobacterium [49] . Autophagy is a host defense mechanism against Mtb. Boosting autophagy could be an effective strategy to promote the eradication of the mycobacteria. Hence, a number of host factors that are involved in the regulation of autophagy were explored as the target of RNAi, including Bfl-1/A1 [152] , Rap22a [153] , Ras homologue enriched in brain (Rheb) [154] and UV radiation resistance-associated gene (UVRAG) [155] . Down-regulation of these factors promoted autophagosome formation and reduced the bacterial growth. However, the existing studies of using RNAi to suppress host factors are preliminary and in vivo data is lacking. Moreover, it was recently reported that autophagy pathway may not be essential for restricting Mtb growth [156] . Further investigations are required to understand the relationship between Mtb infection and autophagy pathway, and to better position the approach of RNAi for the control of tuberculosis infection.