Department of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), Rostock University Medical Center, Rostock, Germany; Faculty of Interdisciplinary Research, Department Life, Light & Matter, University Rostock, Rostock, Germany.
Institute of Genome Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany.
Adv Drug Deliv Rev. 2021 Dec;179:114002. doi: 10.1016/j.addr.2021.114002. Epub 2021 Oct 13.
After thirty years of intensive research shaping and optimizing the technology, the approval of the first mRNA-based formulation by the EMA and FDA in order to stop the COVID-19 pandemic was a breakthrough in mRNA research. The astonishing success of these vaccines have brought the mRNA platform into the spotlight of the scientific community. The remarkable persistence of the groundwork is mainly attributed to the exceptional benefits of mRNA application, including the biological origin, immediate but transitory mechanism of action, non-integrative properties, safe and relatively simple manufacturing as well as the flexibility to produce any desired protein. Based on these advantages, a practical implementation of in vitro transcribed mRNA has been considered in most areas of medicine. In this review, we discuss the key preconditions for the rise of the mRNA in the medical field, including the unique structural and functional features of the mRNA molecule and its vehicles, which are crucial aspects for a production of potent mRNA-based therapeutics. Further, we focus on the utility of mRNA tools particularly in the scope of regenerative medicine, i.e. cell reprogramming approaches or manipulation strategies for targeted tissue restoration. Finally, we highlight the strong clinical potential but also the remaining hurdles to overcome for the mRNA-based regenerative therapy, which is only a few steps away from becoming a reality.
经过三十年的密集研究和技术优化，EMA 和 FDA 批准了第一种基于 mRNA 的制剂以阻止 COVID-19 大流行，这是 mRNA 研究的突破。这些疫苗的惊人成功使 mRNA 平台成为科学界的焦点。这项基础工作的显著持久性主要归因于 mRNA 应用的特殊优势，包括其生物学起源、即时但短暂的作用机制、非整合特性、安全且相对简单的制造以及生产任何所需蛋白质的灵活性。基于这些优势，体外转录的 mRNA 在医学的大多数领域都被认为具有实际可行性。在这篇综述中，我们讨论了 mRNA 在医学领域兴起的关键前提条件，包括 mRNA 分子及其载体的独特结构和功能特征，这些都是生产有效 mRNA 治疗药物的关键方面。此外，我们还重点介绍了 mRNA 工具在再生医学中的应用，即细胞重编程方法或靶向组织修复的操作策略。最后，我们强调了 mRNA 为基础的再生疗法具有强大的临床潜力，但仍有许多障碍需要克服，这项疗法离成为现实仅几步之遥。
