Advances in mRNA-Lipid Nanoparticle Engineering for Immune Cell Targeting and Immune Modulation.

IF 9.1 2区材料科学 Q1 CHEMISTRY, PHYSICAL

Small Methods Pub Date : 2025-09-16 DOI:10.1002/smtd.202501401

Cheesue Kim, Yeji Lee, Hyukjin Lee, Byung-Soo Kim

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引用次数: 0

Abstract

Immunotherapy has transformed therapeutic paradigms, especially in oncology, by leveraging antibodies, cytokines, and cell-based strategies. In recent years, immunotherapy has expanded its impact to combat a broad spectrum of diseases, including fibrotic, autoimmune, and infectious disorders. Messenger RNA (mRNA)-based platforms offer distinct advantages for immunotherapy by enabling in vivo synthesis of proteins with native post-translational modifications to enhance bioactivity and reduce immunogenicity. mRNA also allows non-viral, transient reprogramming of immune cells in vivo, supporting scalable manufacturing and eliminating the risk of insertional mutagenesis. However, naked mRNA faces clinical limitations including inherent instability, poor cellular uptake, and non-targeted delivery. Lipid nanoparticles (LNPs) can overcome these challenges by encapsulating mRNA for protected and efficient delivery to target cells. Importantly, recent advances have demonstrated the potential of mRNA-LNPs to modulate immune cell function with cell-type specificity, enhancing therapeutic precision. This review highlights progress in engineering mRNA-LNPs for targeted immune cell delivery, strategies for immune cell-specific modulation, and applications across immune-related pathologies. Design considerations to improve delivery efficiency and immunological outcomes are also discussed, supporting the clinical translation of mRNA-LNP immunotherapies.

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mrna -脂质纳米粒工程在免疫细胞靶向和免疫调节中的研究进展。

免疫疗法通过利用抗体、细胞因子和基于细胞的策略，已经改变了治疗范式，特别是在肿瘤学领域。近年来，免疫疗法已扩大其影响，以对抗广泛的疾病，包括纤维化，自身免疫性疾病和感染性疾病。基于信使RNA （mRNA）的平台为免疫治疗提供了独特的优势，它能够在体内合成具有天然翻译后修饰的蛋白质，以增强生物活性并降低免疫原性。mRNA还允许在体内对免疫细胞进行非病毒的瞬时重编程，支持可扩展的制造并消除插入突变的风险。然而，裸mRNA面临着临床局限性，包括固有的不稳定性、细胞摄取不良和非靶向递送。脂质纳米颗粒（LNPs）可以通过封装mRNA以保护和有效地递送到靶细胞来克服这些挑战。重要的是，最近的进展已经证明mRNA-LNPs具有细胞类型特异性调节免疫细胞功能的潜力，提高了治疗精度。本文综述了mRNA-LNPs在靶向免疫细胞递送、免疫细胞特异性调节策略以及在免疫相关病理中的应用方面的进展。本文还讨论了提高递送效率和免疫结果的设计考虑，支持mRNA-LNP免疫疗法的临床翻译。

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

Small Methods Materials Science-General Materials Science

CiteScore

17.40

自引率

1.60%

发文量

347

期刊介绍： Small Methods is a multidisciplinary journal that publishes groundbreaking research on methods relevant to nano- and microscale research. It welcomes contributions from the fields of materials science, biomedical science, chemistry, and physics, showcasing the latest advancements in experimental techniques. With a notable 2022 Impact Factor of 12.4 (Journal Citation Reports, Clarivate Analytics, 2023), Small Methods is recognized for its significant impact on the scientific community. The online ISSN for Small Methods is 2366-9608.