Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, PR China.
Mol Cancer. 2021 Feb 16;20(1):33. doi: 10.1186/s12943-021-01311-z.
mRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases.
mRNA 疫苗由于其在安全性、有效性和工业生产方面的优势，具有巨大的抗癌和抗病毒潜力。近几十年来，我们已经见证了通过序列优化开发出的不同种类的 mRNA，以克服 mRNA 免疫原性过高、不稳定和低效的缺点。基于免疫学研究，mRNA 疫苗与免疫佐剂和各种递药策略相结合。除了序列优化，mRNA 递药策略的辅助是另一种稳定 mRNA 并提高其疗效的方法。增加抗原反应性的研究深入了解了 mRNA 诱导的固有免疫和适应性免疫，而没有抗体依赖性增强活性。因此，为了解决这个问题，科学家们进一步开发了基于载体的 mRNA 疫苗（基于脂质的递药、基于聚合物的递药、基于肽的递药、类病毒复制子颗粒和阳离子纳米乳液）、裸 mRNA 疫苗和树突状细胞基于 mRNA 疫苗。本文将讨论 mRNA 疫苗的分子生物学和潜在的抗病毒和抗肿瘤机制，介绍其免疫学现象、递药策略、在 2019 年冠状病毒病（COVID-19）中的重要性以及针对癌症和病毒疾病的相关临床试验。最后，我们将讨论 mRNA 疫苗在对抗细菌和寄生虫疾病方面的挑战。
