2022 Fiscal Year Final Research Report
Development of peptide-ligand modified LNP for microRNA inhibition in tumor tissues.
Project/Area Number |
20K07673
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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 50020:Tumor diagnostics and therapeutics-related
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Research Institution | Chiba University |
Principal Investigator |
Haraguchi Takeshi 千葉大学, 真菌医学研究センター, 特任准教授 (10549455)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 核酸医薬 / DDS / LNP / アクティブターゲッティング / 腫瘍 / microRNA |
Outline of Final Research Achievements |
To develop tumor tissue targeted lipid nanoparticles (LNP) encapsulated with Super-S-TuD, a modified nucleic acid molecule that effectively and specifically inhibits a specific microRNA, we established a simple method to modify the surface layer of Super-S-TuD-encapsulated LNP with a ligand molecule in this study. LNP modified with ligand molecule by this method showed higher transfection efficiency into cancer cells than unmodified LNP. Furthermore, this ligand molecule modified LNP showed high blood retention and accumulation in tumor tissues as well as unmodified LNP. This method enables the preparation of ligand molecule modified Super-S-TuD-encapsulated LNP which has enhanced delivery efficiency into cancer cells and suitable pharmacokinetics for delivery into tumor tissues.
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Free Research Field |
microRNA
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Academic Significance and Societal Importance of the Research Achievements |
本研究の成果により、Super-S-TuD封入LNPの表層にリガンド分子を修飾してがん細胞へのSuper-S-TuDの導入効率を高めることが可能となった。この技術を基盤として腫瘍組織においてmiRNAを阻害する方法論を完成させることで、腫瘍において発現が異常亢進するmiRNAについてIn Vivo試験による機能解析、治療標的としてのmiRNAの探索・評価を行うことが可能となる。そして新たな核酸医薬モダリティの社会実装へとつながるものと期待される。
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