Departmental Bulletin Paper 〈論文・報告〉メジャーグルーブ修飾siRNAによる遺伝子サイレンシング効果

新貝, 恭広  ,  苗村, 円佳  ,  神武, 洋二郎  ,  藤井, 政幸

Small interfering RNA (siRNA) induces RNA interference by forming RNA induced silencing complex (RISC). From a therapeutic point of view, chemical modifications and conjugations of siRNA are powerful strategies to improve their properties toward clinical applications. We can access to siRNA molecules from hydroxyl groups, phosphate backbone, and major groove side and minor groove side of nucleobases. We need to know proper moieties at proper positions for chemical modifications to construct an optimized structure of siRNA. In the present study, we synthesized and evaluated 10 types of siRNAs bearing C5-modified T. All the siRNAs modified in the antisense strand showed reduced silencing efficiencies. It is to be noted the modified positions which intensively reduced silencing efficiencies are well consistent with the positions having major kinks and turns in the crystal structure of guide strandim & Ago2. On the other hand, modification of the sense strand caused less damage to silencing of siRNA and no damage was observed for the modification at s8.

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