In the last decade, messenger ribonucleic acid (mRNA)-based drugs have gained great interest in both immunotherapy and non-immunogenic applications. This surge in interest can be largely attributed to the demonstration of distinct advantages offered by various mRNA molecules, alongside the rapid advancements in nucleic acid delivery systems. It is noteworthy that the immunogenicity of mRNA drugs presents a double-edged sword. In the context of immunotherapy, extra supplementation of adjuvant is generally required for induction of robust immune responses. Conversely, in non-immunotherapeutic scenarios, immune activation is unwanted considering the host tolerability and high expression demand for mRNA-encoded functional proteins. Herein, mainly focused on the linear non-replicating mRNA, we overview the preclinical and clinical progress and prospects of mRNA medicines encompassing vaccines and other therapeutics. We also highlight the importance of focusing on the host-specific variations, including age, gender, pathological condition, and concurrent medication of individual patient, for maximized efficacy and safety upon mRNA administration. Furthermore, we deliberate on the potential challenges that mRNA drugs may encounter in the realm of disease treatment, the current endeavors of improvement, as well as the application prospects for future advancements. Overall, this review aims to present a comprehensive understanding of mRNA-based therapies while illuminating the prospective development and clinical application of mRNA drugs.

在过去十年中，基于信使核糖核酸 （mRNA） 的药物在免疫治疗和非免疫原性应用中都引起了极大的兴趣。这种兴趣的激增在很大程度上可以归因于各种 mRNA 分子提供的独特优势的展示，以及核酸递送系统的快速发展。值得注意的是，mRNA 药物的免疫原性是一把双刃剑。在免疫治疗的情况下，通常需要额外的辅助补充来诱导强大的免疫反应。相反，在非免疫治疗情况下，考虑到宿主耐受性和对 mRNA 编码的功能蛋白的高表达需求，免疫激活是不需要的。本文主要关注线性非复制 mRNA，概述了包括疫苗和其他疗法在内的 mRNA 药物的临床前和临床进展和前景。我们还强调了关注宿主特异性变化的重要性，包括个体患者的年龄、性别、病理状况和并发药物治疗，以最大限度地提高 mRNA 给药的疗效和安全性。此外，我们讨论了 mRNA 药物在疾病治疗领域可能遇到的潜在挑战、目前的改进努力以及未来进展的应用前景。总体而言，本综述旨在全面了解基于 mRNA 的疗法，同时阐明 mRNA 药物的前瞻性开发和临床应用。