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However, it still poses the challenges of accumulation in target sites and reducing off-target effects. Aerosol gene delivery for the treatment of pulmonary diseases has the advantages of high lung accumulation, specific targeting and fewer systemic side effects. However, the key challenge is selecting the appropriate formulation for aerosol gene delivery that can overcome physiological barriers. There are numerous existing gene carriers under study, including viral vectors and non-viral vectors. With the development of biomaterials, more biocompatible substances have applied gene delivery via inhalation. Furthermore, many types of genes can be delivered through aerosol inhalation, such as DNA, mRNA, siRNA and CRISPR\/Cas9. Aerosol delivery of different types of genes has proven to be efficient in the treatment of many diseases such as SARS-CoV-2, cystic fibrosis and lung cancer. In this paper, we provide a comprehensive review of the ongoing research on aerosol gene delivery therapy, including the basic respiratory system, different types of gene carriers, different types of carried genes and clinical applications.<\/jats:p>","DOI":"10.3390\/biom14080904","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T08:40:04Z","timestamp":1721896804000},"page":"904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Aerosol Inhalation of Gene Delivery Therapy for Pulmonary Diseases"],"prefix":"10.3390","volume":"14","author":[{"given":"Yiheng","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hecheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.addr.2014.02.001","article-title":"Challenges for inhaled drug discovery and development: Induced alveolar macrophage responses","volume":"71","author":"Forbes","year":"2014","journal-title":"Adv. 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