| Project/Area Number |
18K19889
|
|---|
| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Medium-sized Section 90:Biomedical engineering and related fields
|
|---|
| Research Institution | Hokkaido University |
|---|
Principal Investigator |
Sato Yusuke 北海道大学, 薬学研究院, 助教 (10735624)
|
|---|
| Project Period (FY) |
2018-06-29 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
|
|---|
| Keywords | 脂質ナノ粒子 / 粒子径 / 足場構造 / 遺伝子ノックダウン / マイクロ流体デバイス / 粒径制御 / 核酸送達 / がん治療 / siRNA / 組織浸透 |
|---|
| Outline of Final Research Achievements |
Despite the fact that development of small-sized lipid nanoparticles are important for improved tissue penetration and efficient nucleic acid delivery, their poor stability and intracellular trafficking significantly hinders their use as potent small-sized lipid nanoparticles. In this study, inspired by the mechanism for the reduced potency, small-sized and potent short interfering RNA-loaded lipid nanoparticles were developed. The mechanism was analyzed from viewpoint of hydrophobic scaffold structure of pH-sensitive cationic lipid.
|
| Academic Significance and Societal Importance of the Research Achievements |
極小粒子径と高いsiRNA送達効率を両立可能な脂質ナノ粒子製剤を見出し、その処方最適化とメカニズム解明に成功した。pH感受性カチオン性脂質の足場鎖長が中性リン脂質との混和性に影響を与え、高い遺伝子ノックダウン活性に寄与していることが明らかとなった。本知見は今後の核酸搭載脂質ナノ粒子開発における合理的な脂質設計および製剤処方検討の指針になると期待される。また、組織浸透性が課題となっているナノ医薬によるがん治療の実現や核酸ナノ粒子製剤の侵襲性の低い投与経路への応用に期待される。
|
