Development of anti-miRNA oligonucleotides with stable duplexes to control cardiac diseases.

2016 Fiscal Year Final Research Report

• Project/Area Number: 25293030
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Komatsu Yasuo 国立研究開発法人産業技術総合研究所, 生物プロセス研究部門, 研究グループ長 (30271670)
• Co-Investigator(Kenkyū-buntansha): 南川 典昭 徳島大学, 大学院医歯薬学研究部, 教授 (40209820) ; 平野 悠 国立研究開発法人産業技術総合研究所, 生物プロセス研究部門, 主任研究員 (70415735)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: microRNA / アンチセンス / 核酸医薬 / RNA / クロスリンク

Outline of Final Research Achievements

We had previously developed an interstrand cross-link (CL) that covalently conjugates a pair of apurinuc/apyrimidinic sites (AP sites) on complementary DNA duplex. We first examined whether the AP site-based cross-link could be applied to complementary 2′-O-methyl RNA (MeRNA) duplexes. Next, we prepared several MeRNA-based anti-miRNA oligonucleotides (AMOs) having CL duplex at the end(s) of the antisense strand, and investigated relationship between the miRNA inhibition activity and the AMO structure. Interestingly, the AMO having the CL-duplex at both terminals exhibited the highest activity and the inhibitory activity was largely affected by the positions of the duplex in AMO molecules. These results indicate the potency of the present structural basis for developing AMO as therapeutic applications.

Free Research Field

核酸化学