2021 Fiscal Year Final Research Report
Analysis of lymphocyte antigen 6 complex, locus A (Ly6a) and elucidation of gymnosis mechanism
| Project/Area Number |
20K16001
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Nigata University of Phermacy and Applied Life Sciences |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | 核酸医薬 / Ly6a |
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| Outline of Final Research Achievements |
Single stranded oligonucleotides (ssOligos) can be taken up by living cells without carrier molecules, a large part of incorporated ssOligos are trapped in the endosomes and do not exert therapeutic effects. To improve their therapeutic effects, it would be important to elucidate the mechanism of cellular uptake and intracellular trafficking of ssOligos. In this study, we investigated how Ly6a affects cellular uptake and intracellular trafficking of ASOs. Fluorescence microscopic analysis suggested that most of naked ASOs are trafficked to the lysosomes via the endosomes. The data obtained from flow cytometry and fluorescence microscopy together showed that although the Ly6a level barely affects the total cellular uptake of ssOligos, it appears to affect the intracellular trafficking of ssOligos
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| Free Research Field |
核酸医薬
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| Academic Significance and Societal Importance of the Research Achievements |
1本鎖核酸医薬は細胞内にキャリア分子を使用せずに取り込ませることができる。しかし、大多数の1本鎖核酸医薬は細胞内ではエンドソームに取り込まれてしまい治療効果を発揮することができないという問題点もある。それを解決するためには1本鎖核酸の細胞内取り込みメカニズムや細胞内輸送メカニズムを解明することが重要であると考えられる。本研究により上記のメカニズムにLy6aが一部関与していることを明らかになった。よって本研究は、将来的にアンチセンス核酸のような核酸医薬の治療効果増強に繋がる重要な研究だと考えられる。
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