Selection of cell penetrating peptide with evolutionary molecular engineering specialized for siRNA delivery
| Project/Area Number |
17K07232
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor therapeutics
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Tada Seiichi 国立研究開発法人理化学研究所, 創発物性科学研究センター, 研究員 (30598165)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 細胞膜透過ペプチド / cDNAディスプレイ / in vitro セレクション / RNAi / 細胞内導入 / 進化分子工学 / 遺伝子発現抑制 / shRNA / in vitroセレクション / siRNA / 膜透過ペプチド |
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| Outline of Final Research Achievements |
I investigated the development of evolutionary molecular engineering selection method of cell penetrating peptides (CPP) for RNAi intracellular delivery based on gene suppression efficiency. I modified the mRNA for cDNA display selection of CPP with shRNA sequence at 5’ terminus in order to select the CPP based on both of cellular uptake efficiency and gene suppression efficiency. In this study, I developed the method of preparation of shRNA-conjugated cDNA display complex and confirmed the gene expression efficiency of shRNA domain after cell transfection. However, it was also revealed that the yield of shRNA-conjugated cDNA display complex should be improved for the CPP selection using cultured cells based on gene suppression level.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の検討により、cDNAディスプレイによるペプチド選別の際に、複合体に様々な修飾を施す余地があることが確認された。今回は細胞内移行と遺伝子発現抑制に焦点を当てて検討を進めたが、今後の検討によってはcDNAディスプレイ複合体に他の低分子化合物や機能性タンパク質を連結することで、従来選別されていた特定の標的を認識するペプチドの選別のみならず、標的検出や薬物送達・薬効の高低に基づいたペプチド選別を実施する可能性が示唆される。
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Report
(4 results)
Research Products
(3 results)
