Institute of Organic Chemistry and Chemical Biology, Goethe University Frankfurt, Max-von-Laue-Str. 7, DE-60438, Frankfurt, Germany.
Institute of Pharmaceutical Chemistry, Philipps University Marburg, Marbacher Weg 6-10, DE-35032, Marburg, Germany.
Chem Biodivers. 2020 Jul;17(7):e2000272. doi: 10.1002/cbdv.202000272. Epub 2020 Jun 25.
Dysregulation of miRNAs is connected with a multitude of diseases for which antagomirs and miRNA replacement are discussed as therapeutic options. Here, we suggest an alternative concept based on the redirection of RISCs to non-native target sites. Metabolically stable DNA-LNA mixmers are used to mediate the binding of RISCs to mRNAs without any direct base complementarity to the presented guide RNA strand. Physical redirection of a dye-labeled miRNA model and of specific miRNA-programmed RISC fractions present in HeLa extracts is demonstrated by pull-down experiments with biotinylated capture oligonucleotides.
miRNA 的失调与多种疾病有关，针对这些疾病，反义寡核苷酸和 miRNA 替代被认为是治疗的选择。在这里，我们提出了一种基于重新导向 RISCs 到非天然靶位的替代概念。代谢稳定的 DNA-LNA 混合体用于介导 RISCs 与 mRNAs 的结合，而与呈现的向导 RNA 链没有任何直接的碱基互补性。通过用生物素标记的捕获寡核苷酸进行下拉实验，证明了染料标记的 miRNA 模型和 HeLa 提取物中特定 miRNA 编程的 RISC 分数的物理重定向。
