| 研究課題/領域番号 |
23KJ1297
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| 研究種目 |
特別研究員奨励費
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| 配分区分 | 基金 |
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| 応募区分 | 国内 |
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| 審査区分 |
小区分90120:生体材料学関連
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| 研究機関 | 京都大学 |
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研究代表者 |
HUO WENTING 京都大学, 工学研究科, 特別研究員(DC2)
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| 研究期間 (年度) |
2023-04-25 – 2025-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
1,800千円 (直接経費: 1,800千円)
2024年度: 900千円 (直接経費: 900千円)
2023年度: 900千円 (直接経費: 900千円)
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| キーワード | drug delivery / tetraphenylethene |
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| 研究開始時の研究の概要 |
Gene therapy is a powerful tool which has the potential to cure diseases permanently. But it's still not widely available to patients because it's hard to get the negatively charged gene molecules into the right cells. Therefore, it's urgent to develop efficient delivery strategies for gene therapy.
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| 研究実績の概要 |
Molecules like oligonucleotides struggle to cross cell membranes due to their polar and charged nature. To overcome this, we developed a light-triggered twistable tetraphenylethene derivative, TPE-C-N, which facilitates their entry into cells through an endocytosis-independent pathway. This method successfully transports peptides and oligonucleotides with molecular weights from 1000 to 5000 Daltons. This new intracellular delivery method proposed can transport both negatively and positively charged molecule without the need for additional chemical modifications and does not require the inefficient endosomal escape. It is foreseeable that this research will inject new vitality into the development of drug delivery systems.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
In this research, our goal is to enhance the delivery efficiency of oligonucleotide therapeutics from 0.1% to approximately 10%. To achieve this, we developed a new strategy that utilizes intramolecular motions to disturb the cell membrane. Tetraphenylethene (TPE) is notable because its central double bond is planar in ground states but becomes twisted in excited states. Consequently, we chose TPE as the light-triggered, twistable backbone. To attach to cell membranes, the TPE backbone was functionalized with hydrophobic anchors. Optimizing the molecular design to balance solubility and membrane attachment required considerable effort. Ultimately, we synthesized TPE-C-N, which successfully increased the delivery efficiency of oligonucleotide therapeutics from 0.1% to approximately 10%.
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| 今後の研究の推進方策 |
In 2024, we plan to develop delivery systems based on various molecular backbones capable of photoinduced intramolecular motions, thereby comprehensively validating the universality of our proposed delivery strategy. To date, we have achieved significant progress in creating light-controllable drug delivery systems using tetraphenylethene. However, the mechanisms by which these systems disturb cell membranes remain unclear. Exploring new molecular backbones will help establish this novel light-controlled delivery system, addressing the gap in the delivery of negatively charged therapeutics. To refine the molecular design, including the twist angle and displacement associated with intramolecular motions, it is essential to study other molecular backbones featuring diverse motion models.
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