2022 Fiscal Year Final Research Report
Development of a novel therapeutic method for liver fibrosis by introducing siRNA using a liver-targeted ternary complex
Project/Area Number |
20K12649
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 90120:Biomaterials-related
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Research Institution | Nagasaki University |
Principal Investigator |
Kurosaki Tomoaki 長崎大学, 医歯薬学総合研究科(薬学系), 助教 (00582016)
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Co-Investigator(Kenkyū-buntansha) |
佐々木 均 長崎大学, 熱帯医学研究所, 特命教授 (00170689)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | ナノ粒子 / 核酸医薬品 / 肝線維症 |
Outline of Final Research Achievements |
In this study, we attempted to develop a novel treatment for liver fibrosis using a liver-targeted ternary complex containing siRNA. siRNA was mixed with various positively charged compounds, and a liver-targeted glycyrrhizic acid was added to the mixture to create a liver-targeted ternary complex. In in vitro study, we selected a most appropriate formulation that was highly effective in introducing siRNA. After intravenous administration of the liver-targeted ternary complex containing TGF-β siRNA to mice, we successfully suppressed the expression of TGF-β in the liver. Further extending our research, we developed safe lung-targeted nanoparticles and succeeded in significantly suppressing fibrosis in a pulmonary fibrosis model using lung-targeted nanoparticles containing TGF-β shRNA.
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Free Research Field |
薬剤学
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Academic Significance and Societal Importance of the Research Achievements |
肝線維症や肺線維症に対しては根治的な治療技術は未だ開発されておらず、盛んに研究がなされている。siRNAやshRNAを発現するpDNAなどの遺伝子・核酸医薬品も盛んに研究されているが、遺伝子・核酸医薬品を標的となる肝臓や肺に選択的に導入できるdrug delivery systemの開発が不可欠である。本研究では非常に効果や選択性の高い肝指向型三元複合体と肺指向型複合体の開発に成功し、肝臓や肺におけるTGF-βの発現を抑制することに成功した。この技術は他のsiRNAやpDNAにも応用可能であり、肝線維症や肺線維症の新しい治療技術となり得ると考えられる。
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