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利用信使核糖核酸-脂质纳米颗粒作为自身免疫性疾病的创新疗法。

Harnessing mRNA-lipid nanoparticles as innovative therapies for autoimmune diseases.

作者信息

Razavi Rose, Kegel Michael, Muscat-Rivera Jenna, Weissman Drew, Melamed Jilian R

机构信息

Penn Institute for RNA Innovation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

Mol Ther Methods Clin Dev. 2025 Aug 18;33(3):101566. doi: 10.1016/j.omtm.2025.101566. eCollection 2025 Sep 11.

Abstract

Autoimmune diseases are chronic conditions where the immune system mistakenly attacks healthy tissues, leading to potentially debilitating symptoms that require lifelong management. There are no cures for autoimmune diseases, and new treatments are urgently needed to improve patient outcomes. This review delves into the compelling advancements and ongoing challenges in harnessing mRNA-lipid nanoparticles (LNPs) as innovative therapies for autoimmune diseases. mRNA-LNPs enable a range of therapeutic approaches to combat autoimmune diseases, including targeted immune cell modulation, tissue regeneration, antigen-specific tolerizing immunotherapy, and chimeric antigen T cell therapies. To successfully advance this promising class of therapies to the clinic, key challenges must be addressed, such as mitigating unwanted inflammation caused by LNPs, overcoming biological barriers to delivery, and ensuring the long-term safety of mRNA-LNPs specifically in autoimmune contexts. Through their modular design, flexible application, and potential for cost-effective production, mRNA-LNP therapies offer exciting clinical potential to transform the management of autoimmune diseases.

摘要

自身免疫性疾病是一种慢性疾病,免疫系统会错误地攻击健康组织,导致可能使人衰弱的症状,需要终身治疗。目前尚无治愈自身免疫性疾病的方法,因此迫切需要新的治疗方法来改善患者的治疗效果。本综述深入探讨了利用信使核糖核酸-脂质纳米颗粒(mRNA-LNP)作为自身免疫性疾病创新疗法所取得的引人注目的进展以及持续存在的挑战。mRNA-LNP能够实现一系列对抗自身免疫性疾病的治疗方法,包括靶向免疫细胞调节、组织再生、抗原特异性耐受性免疫疗法以及嵌合抗原T细胞疗法。为了成功地将这类有前景的疗法推进到临床应用,必须解决一些关键挑战,例如减轻LNP引起的不必要炎症、克服递送的生物屏障以及确保mRNA-LNP在自身免疫背景下的长期安全性。通过其模块化设计、灵活应用以及具有成本效益的生产潜力,mRNA-LNP疗法为改变自身免疫性疾病的治疗管理提供了令人兴奋的临床潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4880/12441705/689b8f229282/fx1.jpg

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