| Project/Area Number |
16H03183
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Tokyo Metropolitan University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
川上 浩良 首都大学東京, 都市環境科学研究科, 教授 (10221897)
根岸 洋一 東京薬科大学, 薬学部, 准教授 (50286978)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2016: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
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| Keywords | 薬物送達システム / モノイオンコンプレックス / プラスミドＤＮＡ / ポリエチレングリコール |
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| Outline of Final Research Achievements |
By optimization of the mono-ion complex (MIC) between our original monocationic PEG and plasmid DNA, we have synthesized omega-amide-pentylimidazolium end-modified PEG with an ester bond for sustainable gene expression in unexplored space. The resulting MIC with pDNA enhanced gene expression after 2 weeks post-transfection in vivo by intramuscular administration in mice. The gene expression was observed in wide area of tibialis muscles with fluorescence microscope. From these results, we have prepared highly-condensed plasmid DNA for delivery to unexplored space in vivo, followed by sustainable gene expression.
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| Academic Significance and Societal Importance of the Research Achievements |
一分子から多分子のタンパク質、RNA、RNA誘導型人工ヌクレアーゼを合成する巨大分子である環状DNAを、MICにより微小粒子化し、生体内の今まで辿り着けなかった空間へ送達することが可能となる。すなわち、生体個体内未踏空間への環状DNA一分子の送達は、多分子の治療薬の送達と同義であり、無侵襲的に、生体個体内の任意の空間におけるタンパク質医薬治療、RNA干渉、ゲノム編集を実現させるDDS基盤技術の確立に繋がるため、難治性疾患治療において重要な意義がある。
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