Inhalable mRNA therapeutics for pulmonary diseases: Challenges in delivery and advances in carrier design

Pulmonary diseases are emerging as one of the leading causes of mortality worldwide, intensifying the urgent need for effective therapeutic interventions. mRNA therapeutics have attracted significant attention due to their therapeutic potential and may represent a new treatment strategy for pulmonary diseases. Delivering mRNA to the lungs via inhalation offers advantages, such as increased local drug concentration and reduced systemic exposure, presenting significant potential to meet the clinical needs of pulmonary diseases. However, the delivery process faces great challenges due to the physicochemical properties of mRNA and the lung's defense mechanisms. This review summarizes recent advancements in mRNA therapeutics for pulmonary inhalation delivery, highlighting the challenges faced in mRNA drug delivery to the lungs. Furthermore, the carrier design for inhaled mRNA delivery and its applications in pulmonary diseases were comprehensively discussed. Finally, we clarify the challenges that inhaled mRNA therapy must overcome before widespread clinical use, aiming to provide more efficient and safe therapeutic options for future pulmonary disease treatments.