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探索免疫介导的炎症性疾病的精准治疗:发挥核酸递送的无限潜力。

Exploring precision treatments in immune-mediated inflammatory diseases: Harnessing the infinite potential of nucleic acid delivery.

作者信息

Xu Lingxiao, Shao Zhenxuan, Fang Xia, Xin Zengfeng, Zhao Shenzhi, Zhang Hongbo, Zhang Yu, Zheng Wenbiao, Yu Xiaohua, Zhang Zengjie, Sun Lingling

机构信息

Department of Orthopedic Surgery The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou China.

Orthopedics Research Institute of Zhejiang University Zhejiang University School of Medicine Hangzhou China.

出版信息

Exploration (Beijing). 2024 May 24;5(1):20230165. doi: 10.1002/EXP.20230165. eCollection 2025 Feb.

Abstract

Immune-mediated inflammatory diseases (IMIDs) impose an immeasurable burden on individuals and society. While the conventional use of immunosuppressants and disease-modifying drugs has provided partial relief and control, their inevitable side effects and limited efficacy cast a shadow over finding a cure. Promising nucleic acid drugs have shown the potential to exert precise effects at the molecular level, with different classes of nucleic acids having regulatory functions through varying mechanisms. For the better delivery of nucleic acids, safe and effective viral vectors and non-viral delivery systems (including liposomes, polymers, etc.) have been intensively explored. Herein, after describing a range of nucleic acid categories and vectors, we focus on the application of therapeutic nucleic acid delivery in various IMIDs, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, multiple sclerosis, asthma, ankylosing spondylitis, systemic lupus erythematosus, and uveitis. Molecules implicated in inflammation and immune dysregulation are abnormally expressed in a series of IMIDs, and their meticulous modulation through nucleic acid therapy results in varying degrees of remission and improvement of these diseases. By synthesizing findings centered on specific molecular targets, this review delivers a systematic elucidation and perspective towards advancing and utilization of nucleic acid therapeutics for managing IMIDs.

摘要

免疫介导的炎症性疾病(IMIDs)给个人和社会带来了难以估量的负担。虽然传统使用的免疫抑制剂和疾病改善药物提供了部分缓解和控制,但它们不可避免的副作用和有限的疗效给找到治愈方法蒙上了阴影。有前景的核酸药物已显示出在分子水平上发挥精确作用的潜力,不同类别的核酸通过不同机制具有调节功能。为了更好地递送核酸,人们对安全有效的病毒载体和非病毒递送系统(包括脂质体、聚合物等)进行了深入探索。在此,在描述了一系列核酸类别和载体之后,我们重点关注治疗性核酸递送在各种IMIDs中的应用,包括类风湿性关节炎、炎症性肠病、银屑病、多发性硬化症、哮喘、强直性脊柱炎、系统性红斑狼疮和葡萄膜炎。与炎症和免疫失调相关的分子在一系列IMIDs中异常表达,通过核酸疗法对其进行精细调节可使这些疾病得到不同程度的缓解和改善。通过综合以特定分子靶点为中心的研究结果,本综述对推进和利用核酸疗法治疗IMIDs进行了系统的阐释并提出了展望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9b4/11875455/adc76af1ab41/EXP2-5-20230165-g009.jpg

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