Development of a novel approach toward nucleic acids-based therapeutics

在这项工作中，我们的目标是制备具有核酸酶抗性和杂交能力的新型化学修饰的RNA分子。此外，我们还期望这些分子具有剪接异常的编辑能力。结果表明，得到的杂交型4‘-硫代核酸具有较好的抗核酸酶活性和杂交能力。在发展的杂交型4‘-硫代核酸中，2’-F-2‘-硫代RNA表现出U1I活性，其原因是U1SnRNA在Pre-mRNA上的募集。为了达到最终目标，我们研究了头对头寡核苷酸的制备。

In this work, we aimed to prepare novel chemically modified RNA molecules possessing nuclease resistance and hybridization ability. In addition, we expected that these molecules exhibit editing ability of splicing abnormality. As a result, the resulting hybrid type of 4’-thionucleic acids showed preferable properties concerning of nuclease resistance and hybridization ability. Among the hybrid type of 4’-thionucleic acids developed, 2’-F-2’-thioRNA showed U1i activity arising from recruitment of U1 snRNA on pre-mRNA. Toward the end goal, we investigated the preparation of head-to-head oligonucleotides.