The treatment of interstitial lung diseases (ILDs) was important to reduce the inflammation or fibrosis within the interstitial space. In recent years, a variety of undruggable ILDs targets were emerged for anti-inflammation and anti-fibrosis therapy. The development of RNA delivery system provided the potential for undruggable targets to the lung via inhalation. However, the RNA delivery systems still faced the challenges, including the protection of the stability of RNA platform, increasing the effective delivery to the targeted cells, and selective escaping of RNA molecules into the cytoplasm. In this review, we first summarized the physiological and biological barriers of RNA inhaled platform. Subsequently, the progress of inhaled RNA delivery system and their therapeutic efficiency have been systematically addressed for the application of ILDs. Finally, in the design of an inhaled RNA delivery system, key factors needed to consider and perspectives are discussed.

RNA delivery system  /  Inhalation  /  Interstitial lung diseases  /  Anti-fibrosis  /  Anti-inflammation  /  RNA stability  /  Targeted delivery system  /  Immune microenvironment