Citation: Kaiqing Zhang, Yue Zhou, Guanlin Wang, Bing Zhu, Ziyu Zhao, Xi Kong, Yihong Gao, Xin Pan, Zhengwei Huang, Chuanbin Wu, Xuejuan Zhang. Pulmonary mRNA delivery systems for the treatment of respiratory diseases: Current advances and challenges[J]. Chinese Chemical Letters, ;2026, 37(8): 111887. doi: 10.1016/j.cclet.2025.111887 shu

Pulmonary mRNA delivery systems for the treatment of respiratory diseases: Current advances and challenges

Kaiqing Zhang ^{a, b, 1} ,
Yue Zhou ^{a, b, 1} ,
Guanlin Wang ^c ,
Bing Zhu ^d ,
Ziyu Zhao ^{a, b} ,
Xi Kong ^{a, b} ,
Yihong Gao ^{a, b} ,
Xin Pan ^c ,
Zhengwei Huang ^{a, b, *,} ,
Chuanbin Wu ^{a, b, *,} ,
Xuejuan Zhang ^{a, b, *,}

a.
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Jinan University, Guangzhou 511443, China
b.
College of Pharmacy, Jinan University, Guangzhou 511443, China
c.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China
d.
Shanghai Fosun Pharmaceutical (Group) Co., Ltd., Shanghai 200233, China

huangzhengw@jnu.edu.cn

chuanbinwu@jnu.edu.cn

zhanghongdou0223@126.com

Received Date: 11 July 2025
Revised Date: 22 September 2025
Accepted Date: 23 September 2025
Available Online: 24 September 2025

Figures(1)

Respiratory diseases constitute a major global health burden, impacting both public health and socioeconomic conditions. Pulmonary mRNA delivery systems are now emerging as a promising therapeutic strategy to treat respiratory diseases, overcoming challenges of conventional mRNA formulations such as low pulmonary bioavailability and adverse side effects. Notably, lipid and polymer nanoparticles integrated into compatible inhaler devices represent the predominant pulmonary mRNA delivery systems. Despite the promising aspects, pulmonary mRNA delivery systems in respiratory diseases treatments face four key challenges, viz. complex airway tract structure, mucociliary clearance system, immune system, and the "last hurdle" intracellular delivery barrier. All these challenges are critical to the treatment effectiveness and safety. Recent progress made on inhalable mRNA delivery methods based on various vectors is highlighted for addressing the above challenges, boosting prospective development of mRNA-based therapies for the treatment of respiratory diseases. This review examines current challenges, strategies, and advances in inhalable mRNA formulations for respiratory diseases and explores prospects for pulmonary mRNA delivery systems, which hold great promise as a next-generation therapeutic platform.
- mRNA,
- Pulmonary mRNA delivery systems,
- Respiratory diseases,
- Immunotherapy,
- Protein replacement therapy,
- Gene editing technology
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沈阳化工大学材料科学与工程学院沈阳 110142