Abstract Messenger RNA based therapeutics have the potential to cause a big revolution in medicine as they can facilitate personalized medicines and allow patients to produce their own therapeutic proteins without the current purification, solubility and inappropriate glycosylation issues associated with recombinant therapeutic proteins. Moreover, a generic and much cheaper production process can be used for mRNA therapeutics as the physicochemical properties of mRNA are independent of its sequence. Furthermore, mRNA vaccines will allow us to respond much quicker to epidemic outbreaks of dangerous infectious diseases as their production is much faster and more flexible than the production of the current vaccines. In the past, the in vivo delivery of mRNA therapeutics was considered as a major bottleneck. However, very recently it has been demonstrated that in vivo delivery issues like low cellular uptake and in vivo degradation by nucleases can be overcome by formulating the therapeutic mRNA into nanoparticles. In this review, we describe the different synthetic mRNA platforms, their production and purification, strategies to tackle the inherent innate immunogenicity of synthetic mRNA, the recent progress in the development of nanoformulations for the in vivo delivery of mRNA, as well as the efficacy and safety of mRNA therapeutics in recent clinical trials.

中文翻译：

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mRNA疗法传递了一个充满希望的信息

摘要 基于信使 RNA 的疗法有可能引发医学大革命，因为它们可以促进个性化药物，并允许患者生产自己的治疗性蛋白质，而无需目前与重组治疗性蛋白质相关的纯化、溶解性和不适当的糖基化问题。此外，由于 mRNA 的理化特性与其序列无关，因此可以将通用且便宜得多的生产过程用于 mRNA 治疗。此外，mRNA 疫苗将使我们能够更快地对危险传染病的流行爆发做出反应，因为它们的生产比当前疫苗的生产更快、更灵活。过去，mRNA 疗法的体内递送被认为是一个主要瓶颈。然而，最近已经证明，通过将治疗性 mRNA 配制成纳米颗粒，可以克服体内递送问题，如细胞摄取低和核酸酶在体内降解。在这篇综述中，我们描述了不同的合成 mRNA 平台、它们的生产和纯化、解决合成 mRNA 固有的先天免疫原性的策略、用于 mRNA 体内递送的纳米制剂开发的最新进展，以及其功效和作用。 mRNA 疗法在最近的临床试验中的安全性。