The chaperone ability of nucleic acid clip nanogels

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K12077
• 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: Kyoto University
• Principal Investigator: Sawada Shin-ichi 京都大学, 工学研究科, 助教 (50444104)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 自己組織化 / 核酸 / 刺激応答性 / ナノゲル / DDS

Outline of Final Research Achievements

It was found that water-soluble polysaccharides (pullulan) containing 6-mer oligonucleotides partially replaced with BNA and LNA, which are bridged (locked) nucleic acids, form assembled particles (nucleic acid clipping-nanogels) about 100 nm in water by double-strand formation of the oligonucleic acids. In addition, the FRET (fluorescence resonance energy transfer) associated with nanogel formation was observed in oligonucleic acid-substituted pullulans having complementary sequences modified with two types of fluorescent probes, and the assembling behavior of the nanogels could be analyzed by fluorescence measurement. It was also found that the nucleic acid clip nanogels can complex with CpG, a 20-mer DNA known as an immunostimulatory molecule, and that they showed cellular delivery and CpG activity.

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Academic Significance and Societal Importance of the Research Achievements

DNAを代表とする核酸同士の結合力を利用してナノサイズの微粒子を形成させることを考えた。プルランは糖が連なった紐状の構造をしており、食品の増粘剤などに利用されている。このプルランにごく短いDNAを結合させた分子を設計、合成した。DNA鎖が短い場合その結合は非常に弱いが、DNA鎖の中に部分的に結合力を強める人工的に設計合成された核酸を加えることでナノサイズの微粒子を創り出すことに成功した。このような微粒子はほとんど報告例が無く、学術的な意義は高い。また、薬となりうる核酸を体内で運ぶための運搬体としての応用も期待できる。