We report, herein, a new class of RNAi trigger molecules based on the unconventional parallel hybridization of two oligonucleotide chains. We have prepared and studied several parallel stranded (ps) duplexes, in which the parallel orientation is achieved through incorporation of isoguanine and isocytosine to form reverse Watson-Crick base pairs in ps-DNA:DNA, ps-DNA:RNA, ps-(DNA-2′F-ANA):RNA, and ps-DNA:2′F-RNA duplexes. The formation of these duplexes was confirmed by UV melting experiments, FRET and CD studies. In addition, NMR structural studies were conducted on a ps-DNA:RNA hybrid for the first time. Finally, we provide evidence for the unprecedented finding that ps-DNA:RNA and ps-DNA:2′F-RNA hybrids can engage the RNAi pathway to silence gene expression in vitro.

中文翻译：

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具有平行方向的化学修饰的DNA-RNA杂种的结构特性和基因沉默活性

我们在此报告了基于两条寡核苷酸链的非常规平行杂交的一类新的RNAi触发分子。我们已经准备并研究了数个平行链（ps）双链体，其中平行方向是通过将异鸟嘌呤和异胞嘧啶并入以在ps -DNA：DNA，ps -DNA  ：RNA，  ps-（ DNA-2'F-ANA）：RNA和ps -DNA：2'F-RNA双链体。通过UV熔融实验，FRET和CD研究证实了这些双链体的形成。此外，NMR结构研究是首次在ps -DNA：RNA杂化物上进行的。最后，我们为史无前例的发现提供了证据，ps -DNA ：RNA和 ps -DNA：2'F-RNA杂种可以通过RNAi途径沉默体外的基因表达。