The success of mRNA vaccines against COVID-19 is nothing short of a medical revolution. Given its chemical lability the use of mRNA as a therapeutic has been counterintuitive and met with skepticism. The development of mRNA-based COVID-19 vaccines was the culmination of long and painstaking efforts by many investigators spanning over 30 years and culminating with the seminal studies of Kariko and Weissman. This review will describe one chapter in this saga, studies that have shown that mRNA can function as a therapeutic. It started with our seminal observation that dendritic cells (DCs) transfected with mRNA in vitro administered to mice inhibits tumor growth, and led to first-in-human clinical trials with mRNA vaccines in cancer patients. The clinical development of this patient-specific DCs-mRNA approach and use on a larger scale was hindered by the challenges associated with personalized cell therapies. Confirmed and extended by many investigators, these studies did serve as impetus and motivation that led scientists to persevere, eventually leading to the development of simple, broadly applicable, and highly effective protocols of directly injecting mRNA into patients, culminating in the COVID-19 mRNA vaccines.

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寻找 mRNA 疫苗

针对 COVID-19 的 mRNA 疫苗的成功无异于一场医学革命。鉴于其化学不稳定性，使用 mRNA 作为治疗剂是违反直觉的，并遭到怀疑。基于 mRNA 的 COVID-19 疫苗的开发是许多研究人员 30 多年来长期艰苦努力的结晶，并以 Kariko 和 Weissman 的开创性研究而告终。这篇综述将描述这个传奇的一章，研究表明 mRNA 可以起到治疗作用。它始于我们的开创性观察，即在体外用 mRNA 转染树突状细胞 (DC)给予小鼠抑制肿瘤生长，并导致在癌症患者中使用 mRNA 疫苗进行首次人体临床试验。这种患者特异性 DCs-mRNA 方法的临床开发和更大规模的使用受到与个性化细胞疗法相关的挑战的阻碍。得到许多研究人员的证实和扩展，这些研究确实成为促使科学家坚持不懈的推动力和动力，最终导致开发出简单、广泛适用且高效的直接向患者注射 mRNA 的方案，最终导致 COVID-19 mRNA疫苗。