Chinese Traditional and Herbal Drugs. 2026, 57(13): 5318-5329.
The incidence and mortality of pulmonary diseases remain persistently high. Conventional therapeutic modalities encounter restrictions, including drug resistance and notable side effects, underscoring the urgent need for novel treatment strategies. Nucleic acid drugs, with their strong target specificity and long-lasting effects, provide a promising new direction for treating pulmonary diseases. Meanwhile, traditional Chinese medicine (TCM), with its extensive theoretical and practical foundation the prevention and treatment of pulmonary diseases, offers innovative intervention strategies through its derived nucleic acid components, which can function via trans-kingdom regulatory mechanisms. This paper explores the potential of TCM-derived nucleic acid drugs as an emerging trans-kingdom therapeutic strategy. Guided by TCM theory, it systematically elaborates drug, type, mechanisms of action, and advances in areas such as drug stability and delivery efficiency, as well as the unique advantages of these agents. Furthermore, the article reviews the application status of nucleic acid drugs in various pulmonary diseases, including chronic obstructive pulmonary disease, asthma, pneumonia, lung cancer, acute lung injury, pulmonary fibrosis, and acute respiratory distress syndrome. Finally, the discussion then addresses the current challenges and future prospects to inform the theoretical foundation and research ideas for the systematic development of this drug class.