Therapeutic Effect of Galactosyltransferase- and Sialyltransferase-encoding mRNA in Rheumatoid Arthritis.

IF 12.1 1区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Molecular Therapy Pub Date : 2025-06-13 DOI:10.1016/j.ymthe.2025.06.018

Xinyi Peng,Yingyu Li,Xiu Sun,Guoru Ren,Haojun Li,Xiaocheng Wang,Peng George Wang,Qingwen Wang,Yang Ji

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引用次数: 0

Abstract

Glycoengineering of IgG, particularly Fc glycosylation, holds significant promise for treating autoimmune diseases by modulating antibody effector functions. However, methods that precisely control IgG glycosylation profiles in vivo are still lacking. In this study, by delivering mRNAs encoding the glycosyltransferases B4GALT1 and ST6GAL1 intravenously, we successfully expressed functional enzymes and demonstrated therapeutic benefits in rheumatoid arthritis animal models in a platelet-dependent manner. We further verified that intra-articular administration effectively ameliorated collagen-induced arthritis in rats. Our findings demonstrate that IgG galactosylation and sialylation, modulated by mRNA drug technology, shift immune responses from pro-inflammatory to anti-inflammatory states, similar to the mechanisms of intravenous immunoglobulin (IVIG) therapies. This study establishes glycosyltransferase-encoding mRNA-LNP technology as a versatile platform for modulating in vivo IgG glycosylation and treating associated diseases.

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半乳糖转移酶和唾液转移酶编码mRNA对类风湿关节炎的治疗作用。

IgG的糖工程，特别是Fc糖基化，通过调节抗体效应功能来治疗自身免疫性疾病具有重要的前景。然而，精确控制体内IgG糖基化谱的方法仍然缺乏。在这项研究中，通过静脉传递编码糖基转移酶B4GALT1和ST6GAL1的mrna，我们成功地表达了功能酶，并以血小板依赖的方式在类风湿性关节炎动物模型中证明了治疗效果。我们进一步证实关节内给药能有效改善大鼠胶原诱导的关节炎。我们的研究结果表明，IgG半乳糖基化和唾液酰化在mRNA药物技术的调节下，将免疫反应从促炎状态转变为抗炎状态，类似于静脉注射免疫球蛋白（IVIG）治疗的机制。本研究建立了糖基转移酶编码mRNA-LNP技术作为调节体内IgG糖基化和治疗相关疾病的通用平台。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Therapy 医学-生物工程与应用微生物

CiteScore

19.20

自引率

3.20%

发文量

357

审稿时长

3 months

期刊介绍： Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.