BioNTech RNA Pharmaceuticals GmbH, An der Goldgrube 12, 55131, Mainz, Germany.
Curr Top Microbiol Immunol. 2017;405:145-164. doi: 10.1007/82_2017_509.
During the last decade, mRNA became increasingly recognized as a versatile tool for the development of new innovative therapeutics. Especially for vaccine development, mRNA is of outstanding interest and numerous clinical trials have been initiated. Strikingly, all of these studies have proven that large-scale GMP production of mRNA is feasible and concordantly report a favorable safety profile of mRNA vaccines. Induction of T-cell immunity is a multi-faceted process comprising antigen acquisition, antigen processing and presentation, as well as immune stimulation. The effectiveness of mRNA vaccines is critically dependent on making the antigen(s) of interest available to professional antigen-presenting cells, especially DCs. Efficient delivery of mRNA into DCs in vivo remains a major challenge in the mRNA vaccine field. This review summarizes the principles of mRNA vaccines and highlights the importance of in vivo mRNA delivery and recent advances in harnessing their therapeutic potential.
在过去的十年中,mRNA 作为开发新型创新疗法的多功能工具越来越受到重视。特别是在疫苗开发方面,mRNA 具有突出的兴趣,已经启动了许多临床试验。引人注目的是,所有这些研究都证明了大规模 GMP 生产 mRNA 是可行的,并一致报告了 mRNA 疫苗良好的安全性特征。T 细胞免疫的诱导是一个多方面的过程,包括抗原的获取、抗原的加工和呈递,以及免疫刺激。mRNA 疫苗的有效性在很大程度上取决于使感兴趣的抗原能够被专业抗原呈递细胞,特别是树突状细胞获得。在体内将 mRNA 有效递送至 DC 仍然是 mRNA 疫苗领域的一个主要挑战。本文综述了 mRNA 疫苗的原理,并强调了体内 mRNA 递送至 DC 的重要性以及利用其治疗潜力的最新进展。