李蕾, 赵彩利, 张宁, 李春雷. mRNA-LNP肝外靶向递送的研究进展J. 药学学报, 2025, 60(2): 359-368. DOI: 10.16438/j.0513-4870.2024-0916
引用本文: 李蕾, 赵彩利, 张宁, 李春雷. mRNA-LNP肝外靶向递送的研究进展J. 药学学报, 2025, 60(2): 359-368. DOI: 10.16438/j.0513-4870.2024-0916
LI Lei, ZHAO Cai-li, ZHANG Ning, LI Chun-lei. Research progress on extrahepatic targeted delivery of mRNA-LNPJ. Acta Pharmaceutica Sinica, 2025, 60(2): 359-368. DOI: 10.16438/j.0513-4870.2024-0916
Citation: LI Lei, ZHAO Cai-li, ZHANG Ning, LI Chun-lei. Research progress on extrahepatic targeted delivery of mRNA-LNPJ. Acta Pharmaceutica Sinica, 2025, 60(2): 359-368. DOI: 10.16438/j.0513-4870.2024-0916

mRNA-LNP肝外靶向递送的研究进展

Research progress on extrahepatic targeted delivery of mRNA-LNP

  • 摘要: 信使核糖核酸(messenger ribonucleic acid, mRNA) 是一种极具潜力的治疗药物, 在免疫学、肿瘤学、疫苗和先天性代谢疾病等研究领域具有广阔前景。但由于其自身不稳定且易被核酸酶降解所以需要高效的递送载体。脂质纳米颗粒(lipid nanoparticle, LNP) 具有易于配制、稳定性高、细胞摄取高效、内体逃逸等优点, 是被公认的最成熟的递送载体。然而, LNP在肝脏中的积累严重限制了mRNA-LNP技术在肝脏以外的靶向与治疗。为了克服这一障碍, 研究人员一直专注于通过各种手段以实现肝外组织器官的精确递送。本文主要从内源性靶向、主动靶向和给药途径的选择这3方面阐述LNP器官特异性递送mRNA的研究进展, 以期为后续新型mRNA-LNP递送体系的设计提供思路及方向。

     

    Abstract: Messenger ribonucleic acid (mRNA) is a promising therapeutic drug with great potential in the fields of immunology, oncology, vaccines and inborn metabolic diseases. However, due to its instability and susceptibility to nuclease degradation, efficient delivery vectors are required. Lipid nanoparticles (LNPs) are recognized as the most mature delivery vectors due to their advantages of easy formulation, high stability, efficient cell uptake and endosomal escape. However, the accumulation of LNPs in the liver severely limits the targeting and treatment of mRNA-LNP technology beyond the liver. To overcome this obstacle, researchers have been focusing on various means to achieve precise delivery of extrahepatic tissues and organs. This article mainly expounds the research progress of LNP-specific delivery mRNA from three aspects: endogenous targeting, active targeting and selection of administration route, in order to provide ideas and directions for the design of new mRNA-LNP delivery systems in the future.

     

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