Development of modified U1 snRNA derivatives as new nucleic acid drugs

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K05840
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: Ohkubo Akihiro 東京工業大学, 生命理工学院, 准教授 (60376960)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: U snRNA / スプライシング / 核酸合成

Outline of Final Research Achievements

In this study, we carried out synthesis of a U snRNA by the ligation reactions using four RNA oligomers and RNA ligase. However, the ligation efficiency was very low due to the steric hindrance of the RNA structure. In order to overcome the steric hindrance, we used DNA ligase in the presence of a splint DNA. As a result, we successfully synthesize a U snRNA in an efficient yield.
Moreover, we also synthesized modified U1 and U11 snRNA analogs containing a m3G cap structure under the ligation conditions using DNA ligase in the presence of a splint DNA. At the present, the splicing activities of the U RNAs are evaluated cystic fibrosis model cells.

Free Research Field

生物有機化学

Academic Significance and Societal Importance of the Research Achievements

遺伝子変異によるエキソンの欠落を化学合成したRNAによって阻止する「スプライシングコレクション」は、これまで治療が困難とされてきたスプライシング異常に起因する遺伝子疾患の治療に多いに貢献できると期待される。また、従来の核酸医薬とは全く違った作用機序をもつため、当該分野における貢献度も高いと考えられる。