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非病毒 mRNA 递药材料的研究进展及其作为黑素瘤治疗疫苗的应用

Advances in Nonviral mRNA Delivery Materials and Their Application as Vaccines for Melanoma Therapy.

机构信息

Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.

School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.

出版信息

ACS Appl Bio Mater. 2024 Aug 19;7(8):4894-4913. doi: 10.1021/acsabm.3c00721. Epub 2023 Nov 6.

Abstract

Messenger RNA (mRNA) vaccines are promising platforms for cancer immunotherapy because of their potential to encode for a variety of tumor antigens, high tolerability, and capacity to induce strong antitumor immune responses. However, the clinical translation of mRNA cancer vaccines can be hindered by the inefficient delivery of mRNA . In this review, we provide an overview of mRNA cancer vaccines by discussing their utility in treating melanoma. Specifically, we begin our review by describing the barriers that can impede mRNA delivery to target cells. We then review native mRNA structure and discuss various modification methods shown to enhance mRNA stability and transfection. Next, we outline the advantages and challenges of three nonviral carrier platforms (lipid nanoparticles, polymeric nanoparticles, and lipopolyplexes) frequently used for mRNA delivery. Last, we summarize preclinical and clinical studies that have investigated nonviral mRNA vaccines for the treatment of melanoma. In writing this review, we aim to highlight innovative nonviral strategies designed to address mRNA delivery challenges while emphasizing the exciting potential of mRNA vaccines as next-generation therapies for the treatment of cancers.

摘要

信使 RNA(mRNA)疫苗因其能够编码多种肿瘤抗原、高耐受性和诱导强烈抗肿瘤免疫反应的潜力,成为癌症免疫治疗的有前途的平台。然而,mRNA 的低效传递可能会阻碍 mRNA 癌症疫苗的临床转化。在这篇综述中,我们通过讨论其在治疗黑色素瘤中的应用,对 mRNA 癌症疫苗进行了概述。具体来说,我们首先描述了可能阻碍 mRNA 递送到靶细胞的障碍。然后,我们回顾了天然 mRNA 结构,并讨论了各种已证明可提高 mRNA 稳定性和转染的修饰方法。接下来,我们概述了三种常用于 mRNA 传递的非病毒载体平台(脂质纳米颗粒、聚合物纳米颗粒和脂质体多聚物)的优点和挑战。最后,我们总结了研究非病毒 mRNA 疫苗治疗黑色素瘤的临床前和临床研究。在撰写这篇综述时,我们旨在强调旨在解决 mRNA 传递挑战的创新型非病毒策略,同时强调 mRNA 疫苗作为治疗癌症的下一代疗法的令人兴奋的潜力。

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