Self-assembling hybrid nucleic acid nanodevices for pinpoint delivery of middle-molecule drugs

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K12691
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90120:Biomaterials-related
• Research Institution: Tokyo University of Science
• Principal Investigator: Nishikawa Makiya 東京理科大学, 薬学部薬学科, 教授 (40273437)
• Co-Investigator(Kenkyū-buntansha): 草森 浩輔 東京理科大学, 薬学部薬学科, 講師 (90707407)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 核酸 / 中分子医薬 / 標的化 / リガンド修飾 / タンパク結合 / 体内動態

Outline of Final Research Achievements

In this study, we developed a self-assembling hybrid nucleic acid nanodevice in which a targeting ligand is combined with a nucleic acid nanodevice constructed by self-assembly of nucleic acids to realize pinpoint delivery of middle-molecule drugs such as nucleic acid drugs to the target. The CpG oligodeoxynucleotides (CpG oligos) that activate innate immunity were modified with stearic acid or mannose, which have high binding affinity with serum albumin, as ligands, and these ligands were loaded onto the self-assembled nucleic acid nanodevices. We demonstrated that CpG oligos can be delivered to target antigen-presenting cells with pinpoint accuracy by loading them onto self-assembled nucleic acid nanodevices.

Free Research Field

生物薬剤学

Academic Significance and Societal Importance of the Research Achievements

核酸医薬をはじめとする中分子医薬の開発には、膜透過の改善による投与経路の拡大と体内動態制御による有効性および安全性の向上が求められる。本研究の成果は、核酸医薬の有効性を高めるうえで、核酸ナノ構造体とリガンド修飾を組み合わせた自己組織化型ハイブリッド核酸ナノデバイスが有効であることを示すものである。本成果をもとに核酸医薬をピンポイントで標的細胞に送達可能となれば、開発が進む核酸医薬品の実用化を加速する点で社会的意義も大である。