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

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

Targeting dendritic cells (DCs) in the airways by RNAi is another strategy for the treatment of asthma. DCs are antigen presenting cells that could be found in the airways [5, 201] . They are actively involved in the differentiation of T h 2 cells and hence contribute to the progress of airway inflammation [202] . DCs express co-stimulatory molecules, cluster of differentiation (CD) 80 and 86, on the surface. The binding of CD80/CD86 with CD28 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) molecules on T cells is necessary for priming naive T cells into T h 2 cells [203] . Blocking CD80 and/or CD86 activity with pharmacological inhibitors can inhibit T cell activation and alleviate AHR and pulmonary inflammation in mice exposed to aerosolized allergen challenge [204] . Likewise, intratracheal administration of siRNA targeting CD86 significantly reduced its expression in the airway mucosa of mouse model of allergic asthma. CD86 siRNA treatment also contributed to the amelioration of OVA-induced airway eosinophilia, hyperresponsiveness, the elevations of IgE in the sera and the production of inflammatory cytokines in BALF [171] .