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Inhalable nucleic acid therapeutics for chronic pulmonary disease: Progress, challenges, and prospects
Yangeng Wang1, Wenzhe Xuan1, Chengqiong Mao2
1School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, PR China.
Acta Biomaterialia
|August 2, 2025
Summary
Inhalable nucleic acid therapies offer new hope for chronic lung diseases like COPD and asthma. Developing effective delivery systems is key to overcoming lung barriers and advancing gene therapy for respiratory conditions.
Area of Science:
- Pulmonary Drug Delivery
- Gene Therapy
- Nanomedicine
Background:
- Chronic pulmonary diseases (asthma, COPD, CF, IPF) cause significant morbidity and mortality.
- Current treatments lack molecular-level targeting for disease pathogenesis.
- Nucleic acid therapeutics offer precise gene regulation and pathway modulation.
Purpose of the Study:
- To review recent advances in inhalable nucleic acid delivery platforms for chronic pulmonary diseases.
- To discuss pulmonary biological barriers and strategies to overcome them.
- To outline clinical progress and future directions for inhaled gene therapies.
Main Methods:
- Review of recent scientific literature on inhalable nucleic acid delivery systems.
- Analysis of nanocarrier designs (viral, lipid, polymeric, hybrid).
- Discussion of physiological and pathological barriers in the pulmonary microenvironment.
Main Results:
- Inhalable nucleic acid delivery enables direct, non-invasive lung access with localized effects.
- Various nanocarriers are engineered to improve nucleic acid stability, targeting, and transfection.
- Overcoming lung barriers (mucus, enzymes, macrophages) is crucial for efficacy.
Conclusions:
- Inhalable nucleic acid delivery systems show promise for treating chronic lung diseases.
- Effective nanocarrier design and understanding of pulmonary barriers are critical for clinical translation.
- Further research is needed to accelerate the development of inhaled gene therapies for respiratory disorders.
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