Disruption of the equilibrium between ion secretion and absorption processes by the airway epithelium is central to many muco-obstructive lung diseases including cystic fibrosis (CF). Besides correction of defective folding and function of CFTR, inhibition of amiloride-sensitive epithelia sodium channels (ENaC) has emerged as a bona fide therapeutic strategy to improve mucociliary clearance in patients with CF. The short half-life of amiloride-based ENaC blockers and hyperosmotic therapies have led to the development of novel RNA-based interventions for targeted and sustained reduction of ENaC expression and function in preclinical models of CF. This review summarizes the recent advances in RNA therapeutics targeting ENaC for mutation-agnostic treatment of CF.

气道上皮细胞离子分泌和吸收过程之间平衡的破坏是包括囊性纤维化 (CF) 在内的许多粘液阻塞性肺病的核心。除了纠正 CFTR 的折叠缺陷和功能外，抑制阿米洛利敏感上皮细胞钠通道 (ENaC) 已成为改善 CF 患者粘液纤毛清除的真正治疗策略。基于阿米洛利的 ENaC 阻滞剂和高渗疗法的短半衰期导致开发了新的基于 RNA 的干预措施，用于靶向和持续降低 CF 临床前模型中的 ENaC 表达和功能。这篇综述总结了靶向 ENaC 的 RNA 疗法的最新进展，用于 CF 的突变不可知治疗。