1] TRON Translational Oncology at the University Medical Center of the Johannes Gutenberg University, Langenbeckstrasse 1, 55131 Mainz, Germany. [2] BioNTech Corporation, An der Goldgrube 12, 55131 Mainz, Germany.
1] BioNTech Corporation, An der Goldgrube 12, 55131 Mainz, Germany. [2] Department of Neurosurgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Nat Rev Drug Discov. 2014 Oct;13(10):759-80. doi: 10.1038/nrd4278. Epub 2014 Sep 19.
In vitro transcribed (IVT) mRNA has recently come into focus as a potential new drug class to deliver genetic information. Such synthetic mRNA can be engineered to transiently express proteins by structurally resembling natural mRNA. Advances in addressing the inherent challenges of this drug class, particularly related to controlling the translational efficacy and immunogenicity of the IVTmRNA, provide the basis for a broad range of potential applications. mRNA-based cancer immunotherapies and infectious disease vaccines have entered clinical development. Meanwhile, emerging novel approaches include in vivo delivery of IVT mRNA to replace or supplement proteins, IVT mRNA-based generation of pluripotent stem cells and genome engineering using IVT mRNA-encoded designer nucleases. This Review provides a comprehensive overview of the current state of mRNA-based drug technologies and their applications, and discusses the key challenges and opportunities in developing these into a new class of drugs.
体外转录（IVT）mRNA 最近成为一种潜在的新型药物类别，可用于传递遗传信息。这种合成的 mRNA 可以通过结构上类似于天然 mRNA 来设计成瞬时表达蛋白质。在解决该药物类别的固有挑战方面取得了进展，特别是与控制 IVTmRNA 的翻译效力和免疫原性有关的挑战，为广泛的潜在应用提供了基础。基于 mRNA 的癌症免疫疗法和传染病疫苗已进入临床开发阶段。与此同时，新兴的新方法包括将 IVT mRNA 递送至体内以替代或补充蛋白质、基于 IVT mRNA 的多能干细胞生成以及使用 IVT mRNA 编码的设计核酸酶进行基因组工程。这篇综述全面概述了基于 mRNA 的药物技术及其应用，并讨论了将其开发成一类新药所面临的关键挑战和机遇。
