@article{oai:kindai.repo.nii.ac.jp:00017669, author = {新貝, 恭広 and Shinkai, Yasuhiro and 柏原, 慎一 and Kashihara, Shinichi and 藤井, 啓史 and Fujii, Hirohumi and 峰松, 剛 and Minematsu, Go and 吉永, 尚平 and Yoshinaga, Shouhei and 苗村, 円佳 and Naemura, Madoka and 神武, 洋二郎 and Kotake, Yojiro and 藤井, 政幸 and Fujii, Masayuki}, issue = {24}, journal = {かやのもり:近畿大学産業理工学部研究報告, Reports of Faculty of Humanity-Oriented Science and Engineering, Kindai University}, month = {Jul}, note = {For clinical applications of small interfering RNA (siRNA), chemical structure of siRNA should be optimized to be taken up into cells effectively, resistant to nuclease digestion, incorporated into RNA induced silencing complex (RISC) rapidly and correctly. They should also have minimized off-target effect and maximized turn over number. In this study, we investigated RNA interference (RNAi) efficiencies of siRNAs bearing 5’-amino-5’-deoxythymidine (T*) at 5’-end. The results showed that T* at the 5’-end of the sense strand did not interfere the processes of RISC loading complex (RLC) formation, loading to RISC or cleavage of the passenger strand by human argonaute2 (hAgo2) at all. On the other hand, T* at the 5’-end of the antisense strand gave a fatal damage to siRNA to show almost no silencing effect probably because RISC was destabilized by an electrostatic repulsion between the cationic charge of the ammonium group of T* and the cationic residues in MID domain pocket of hAgo2. These results strongly suggest that a modification of 5’-end of a sense strand with T* will suppress an off-target effect., application/pdf}, pages = {1--5}, title = {〈論文・報告〉化学修飾small interfering RNA (siRNA)による遺伝子サイレンシング}, year = {2016}, yomi = {シンカイ, ヤスヒロ and カシハラ, シンイチ and フジイ, ヒロフミ and ミネマツ, ゴウ and ヨシナガ, ショウヘイ and ナエムラ, マドカ and コウタケ, ヨウジロウ and フジイ, マサユキ} }