Deutsches Krebsforschungszentrum (DKFZ), Division of Mechanisms Regulating Gene Expression, Heidelberg, Germany.
Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg-University Mainz, Mainz, Germany.
Nat Rev Genet. 2024 Feb;25(2):104-122. doi: 10.1038/s41576-023-00645-2. Epub 2023 Sep 15.
The ability of chemical modifications of single nucleotides to alter the electrostatic charge, hydrophobic surface and base pairing of RNA molecules is exploited for the clinical use of stable artificial RNAs such as mRNA vaccines and synthetic small RNA molecules - to increase or decrease the expression of therapeutic proteins. Furthermore, naturally occurring biochemical modifications of nucleotides regulate RNA metabolism and function to modulate crucial cellular processes. Studies showing the mechanisms by which RNA modifications regulate basic cell functions in higher organisms have led to greater understanding of how aberrant RNA modification profiles can cause disease in humans. Together, these basic science discoveries have unravelled the molecular and cellular functions of RNA modifications, have provided new prospects for therapeutic manipulation and have led to a range of innovative clinical approaches.
化学修饰单个核苷酸的能力可以改变 RNA 分子的静电电荷、疏水性表面和碱基配对，这为稳定的人工 RNA 的临床应用（如 mRNA 疫苗和合成的小 RNA 分子）提供了便利，可用于增加或减少治疗性蛋白的表达。此外，核苷酸的自然生化修饰调节 RNA 代谢和功能，从而调节关键的细胞过程。研究表明，RNA 修饰调节高等生物基本细胞功能的机制，使人们对异常 RNA 修饰谱如何导致人类疾病有了更深入的了解。这些基础科学发现共同揭示了 RNA 修饰的分子和细胞功能，为治疗干预提供了新的前景，并带来了一系列创新的临床方法。
