Development of lipid nanoparicles for treatment of hepatic diseases by in vivo genome editing
| Project/Area Number |
17H05052
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Physical pharmacy
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| Research Institution | Hokkaido University |
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Principal Investigator |
Sato Yusuke 北海道大学, 薬学研究院, 助教 (10735624)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥22,880,000 (Direct Cost: ¥17,600,000、Indirect Cost: ¥5,280,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2017: ¥11,700,000 (Direct Cost: ¥9,000,000、Indirect Cost: ¥2,700,000)
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| Keywords | ゲノム編集 / 脂質ナノ粒子 / マイクロ流体デバイス / in vivoゲノム編集 / RNP送達 / pH感受性カチオン性脂質 / 肝疾患治療 / ph感受性カチオン性脂質 / 安全治療域 / タンパク質送達 / RNP / In vivoゲノム編集 / RNA送達 |
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| Outline of Final Research Achievements |
Genome editing is a biotechnology that can disrupt, repair and insert genes of interest and can be applied for fundamental treatment of various hereditary diseases. Development of nanotechnology capable of efficient delivery of genome editing factors is important for medical application. In this study, lipid nanoparticles that deliver CRISPR-Cas protein-gRNA complexes efficiently were developed. From a viewpoint of practical application, microfluidic device-based synthesizing methodology that enables seamless manufacturing scale-up was developed.
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| Academic Significance and Societal Importance of the Research Achievements |
マイクロ流体デバイスによるゲノム編集因子搭載脂質ナノ粒子の連続製造法を世界に先駆けて見出すことに成功した。マイクロ流体デバイスはシームレスな製造スケールアップが可能であることから、核酸ナノ医薬品開発に広く応用されているが、核酸分子と比較して物理化学的に不安定なタンパク質のナノ製剤化へ応用できることを示したことは今後の高分子搭載ナノ粒子製剤開発における意義は大きい。また、製剤最適化により競合技術よりも圧倒的に高い効率で遺伝子ノックアウトを誘導可能な脂質ナノ粒子製剤の同定に成功した。最適化の過程で得られた重要因子に関する情報は今後の製剤開発における指針となると考えられる。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Sato Y, Matsui H, Yamamoto N, Sato R, Munakata T, Kohara M, Harashima H. Highly specific delivery of siRNA to hepatocytes circumvents endothelial cell-mediated lipid nanoparticle-associated toxicity leading to the safe and efficacious decrease in the hepatitis B virus2017
Author(s)
Sato Y, Matsui H, Yamamoto N, Sato R, Munakata T, Kohara M, Harashima H
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Journal Title
J Control Release
Volume: 266
Pages: 216-225
DOI
Related Report
Peer Reviewed
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