Huang Cheng, Li Hongjian, Duan Xing, Zhang Peidong, Qi Shaolong, Du Jianshi, Song Xiangrong, Tong Aiping, Yu Guocan
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, China.
State Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
Acta Pharm Sin B. 2025 May;15(5):2402-2430. doi: 10.1016/j.apsb.2025.03.033. Epub 2025 Mar 19.
RNA-based gene therapy has been widely used for various diseases, and extensive studies have proved that suitable delivery routes greatly help the development of RNA therapeutics. Identifying a safe and effective delivery system is key to realizing RNA therapeutics' clinical translation. Inhalation is a non-invasive pulmonary delivery modality that can enhance the retention of therapeutic agents in the lungs with negligible toxicity, thereby improving patient compliance. Inhaled RNA therapeutics are increasingly becoming an area of focus for researchers; however, only several clinical trials have explored inhaled delivery of RNA for pulmonary diseases. This review presents an overview of recent advances in inhaled delivery systems for RNA therapeutics, including viral and nonviral systems, highlighting state of the art regarding inhalation in the messenger RNA (mRNA) field. We also summarize the applications of mRNA inhalants in infectious and other lung diseases. Simultaneously, the research progresses on small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), and different types of RNA are also discussed to provide new strategies for developing RNA inhalation therapy. Finally, we clarify the challenges inhaled RNA-based therapeutics face before their widespread adoption and provide insights to help advance this exciting field to the bedside.
基于RNA的基因疗法已广泛应用于各种疾病,大量研究证明,合适的给药途径对RNA疗法的发展有很大帮助。确定一个安全有效的递送系统是实现RNA疗法临床转化的关键。吸入是一种非侵入性的肺部给药方式,它能以可忽略不计的毒性增强治疗剂在肺部的滞留,从而提高患者的依从性。吸入式RNA疗法正日益成为研究人员关注的领域;然而,只有几项临床试验探索了RNA用于肺部疾病的吸入给药。本综述概述了RNA疗法吸入递送系统的最新进展,包括病毒和非病毒系统,突出了信使RNA(mRNA)领域吸入技术的最新水平。我们还总结了mRNA吸入剂在感染性和其他肺部疾病中的应用。同时,也讨论了小干扰RNA(siRNA)、反义寡核苷酸(ASO)和不同类型RNA的研究进展,为开发RNA吸入疗法提供新策略。最后,我们阐明了基于RNA的吸入疗法在广泛应用之前所面临的挑战,并提供见解以帮助推动这一令人兴奋的领域走向临床应用。
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