The emergency use authorizations (EUAs) of two mRNA-based severe acute respiratory syndrome coronavirus (SARS-CoV)-2 vaccines approximately 11 months after publication of the viral sequence highlights the transformative potential of this nucleic acid technology. Most clinical applications of mRNA to date have focused on vaccines for infectious disease and cancer for which low doses, low protein expression and local delivery can be effective because of the inherent immunostimulatory properties of some mRNA species and formulations. In addition, work on mRNA-encoded protein or cellular immunotherapies has also begun, for which minimal immune stimulation, high protein expression in target cells and tissues, and the need for repeated administration have led to additional manufacturing and formulation challenges for clinical translation. Building on this momentum, the past year has seen clinical progress with second-generation coronavirus disease 2019 (COVID-19) vaccines, Omicron-specific boosters and vaccines against seasonal influenza, Epstein–Barr virus, human immunodeficiency virus (HIV) and cancer. Here we review the clinical progress of mRNA therapy as well as provide an overview and future outlook of the transformative technology behind these mRNA-based drugs.

在病毒序列公布约 11 个月后，两种基于 mRNA 的严重急性呼吸综合征冠状病毒 (SARS-CoV)-2 疫苗的紧急使用授权 (EUA) 凸显了这种核酸技术的变革潜力。迄今为止，mRNA 的大多数临床应用都集中在传染病和癌症疫苗上，由于某些 mRNA 种类和制剂的固有免疫刺激特性，低剂量、低蛋白表达和局部递送对于这些疫苗是有效的。此外，关于 mRNA 编码的蛋白质或细胞免疫疗法的工作也已经开始，针对这些疗法，最小的免疫刺激、靶细胞和组织中的高蛋白表达以及重复给药的需要导致临床转化面临额外的制造和配方挑战。在这一势头的基础上，过去一年在第二代冠状病毒病 2019 (COVID-19) 疫苗、Omicron 特异性增强剂和针对季节性流感、爱泼斯坦-巴尔病毒、人类免疫缺陷病毒 (HIV) 和癌症的疫苗方面取得了临床进展。在这里，我们回顾了 mRNA 治疗的临床进展，并对这些基于 mRNA 的药物背后的变革技术进行了概述和未来展望。