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用于RNA治疗的吸入式非病毒递送系统。

Inhaled non-viral delivery systems for RNA therapeutics.

作者信息

Huang Cheng, Li Hongjian, Duan Xing, Zhang Peidong, Qi Shaolong, Du Jianshi, Song Xiangrong, Tong Aiping, Yu Guocan

机构信息

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.

出版信息

Acta Pharm Sin B. 2025 May;15(5):2402-2430. doi: 10.1016/j.apsb.2025.03.033. Epub 2025 Mar 19.


DOI:10.1016/j.apsb.2025.03.033
PMID:40487670
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12145032/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/08356b5f05ab/gr13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/223f88d44947/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/0b1897f38927/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/7bc9d1f06082/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/e14a122bfcc3/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/6f6b61526ac5/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/57f3939497a1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/4229bbf69352/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/c5b9b8efd389/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/b65970d55640/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/ea28715091d8/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/c3876f612f24/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/841672349dc9/gr11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/542ebc9aa49e/gr12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/08356b5f05ab/gr13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/223f88d44947/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/0b1897f38927/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/7bc9d1f06082/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/e14a122bfcc3/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/6f6b61526ac5/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/57f3939497a1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/4229bbf69352/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/c5b9b8efd389/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/b65970d55640/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/ea28715091d8/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/c3876f612f24/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/841672349dc9/gr11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/542ebc9aa49e/gr12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b28/12145032/08356b5f05ab/gr13.jpg

相似文献

[1]
Inhaled non-viral delivery systems for RNA therapeutics.

Acta Pharm Sin B. 2025-5

[2]
Inhaled RNA Therapy: From Promise to Reality.

Trends Pharmacol Sci. 2020-10

[3]
From bench side to clinic: Potential and challenges of RNA vaccines and therapeutics in infectious diseases.

Mol Aspects Med. 2021-10

[4]
Inhaled RNA Therapeutics for Obstructive Airway Diseases: Recent Advances and Future Prospects.

Pharmaceutics. 2021-1-28

[5]
Advances in the delivery of RNA therapeutics: from concept to clinical reality.

Genome Med. 2017-6-27

[6]
Progress in microRNA delivery.

J Control Release. 2013-9-25

[7]
siRNA-based delivery systems: Technologies, carriers, applications, and approved products.

Eur J Pharmacol. 2025-6-5

[8]
Non-Viral RNA Therapies for Non-Small Cell Lung Cancer and Their Corresponding Clinical Trials.

Mol Pharm. 2025-4-7

[9]
Advances in mRNA non-viral delivery approaches.

Adv Drug Deliv Rev. 2021-10

[10]
Delivery of RNAi Therapeutics to the Airways-From Bench to Bedside.

Molecules. 2016-9-20

本文引用的文献

[1]
Charge-assisted stabilization of lipid nanoparticles enables inhaled mRNA delivery for mucosal vaccination.

Nat Commun. 2024-11-2

[2]
mRNA therapeutics: New vaccination and beyond.

Fundam Res. 2023-3-16

[3]
Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery .

iScience. 2024-4-23

[4]
Lipid nanoparticles for local delivery of mRNA to the respiratory tract: Effect of PEG-lipid content and administration route.

Eur J Pharm Biopharm. 2024-5

[5]
The application of nanoparticles as advanced drug delivery systems in Attenuating COPD.

Heliyon. 2024-2-1

[6]
Inhaled immunoantimicrobials for the treatment of chronic obstructive pulmonary disease.

Sci Adv. 2024-2-9

[7]
Inhalable extracellular vesicle delivery of IL-12 mRNA to treat lung cancer and promote systemic immunity.

Nat Nanotechnol. 2024-4

[8]
A next-generation inhalable dry powder COVID vaccine.

Nature. 2023-12

[9]
Inhaled RNA drugs to treat lung diseases: Disease-related cells and nano-bio interactions.

Adv Drug Deliv Rev. 2023-12

[10]
Combinatorial development of nebulized mRNA delivery formulations for the lungs.

Nat Nanotechnol. 2024-3

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