信使 RNA (mRNA) 疫苗是有前途的癌症免疫治疗平台，因为它们具有编码多种肿瘤抗原的潜力、高耐受性以及诱导强烈抗肿瘤免疫反应的能力。然而，mRNA 癌症疫苗的临床转化可能会因 mRNA 体内递送效率低下而受到阻碍。在这篇综述中，我们通过讨论 mRNA 癌症疫苗在治疗黑色素瘤中的效用来概述它们。具体来说，我们首先描述阻碍 mRNA 递送至靶细胞的障碍。然后我们回顾天然 mRNA 结构并讨论各种可增强 mRNA 稳定性和转染的修饰方法。接下来，我们概述了常用于 mRNA 递送的三种非病毒载体平台（脂质纳米颗粒、聚合物纳米颗粒和脂多聚复合物）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，我们的目的是强调旨在解决 mRNA 递送挑战的创新非病毒策略，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。

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 vivo. 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.