旭硝子財団助成研究成果報告2024
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42竹内 雄一37Yuichi TAKEUCHI三宅 丈雄38Takeo MIYAKE超音波遺伝学と工学の融合による新しい非侵襲的脳刺激法の開発(2022採択)Development of a novel non-invasive brain stimulation technology with ultrasound and genetic engineering(Project 2022)電気化学と細胞科学の融合による細胞用電動ナノ注射器の開発と細胞治療応用(2022採択)Development of an electric intracellular nanoinjection system by combining electrochemistry and cell science and its application to cell therapy (Project 2022)Transposons (TEs) are endogenous virus-like sequences from viruses that invade the host genome during bio-logical evolution and are widely distributed in biological genomes. The gene structure of retrotransposons (RTEs), which are RNA-type TEs, closely resembles that of retroviruses, suggesting that RTEs may be able to form virus-like particles. Since some RTEs are expressed in wild-type cells, the existence of cell-cell interac-tion by RTE-derived particles was predicted. In this study, RTE-derived extracellular particles were purified and analyzed using cultured cells to determine the specificity of particle-forming RTEs. Furthermore, we at-tempted to elucidate its physiological function by analyzing individual Drosophila.難治性てんかんやうつ病等,薬物抵抗性の神経・精神疾患の症状制御には,脳刺激法による神経活動の直接制御が効果的である.しかしながら,従来用いられてきた脳深部刺激や光遺伝学刺激は電極等の脳実質への刺入に伴う侵襲性が課題であった.そこで本研究では,生体透過性に優れた超音波を利用した非侵襲的脳刺激法の新規開発により,当該課題を解決することを目的とした.当該目的の達成のため,①in vivo超音波遺伝学の開発,②小型超音波照射装置の開発,③非侵襲的かつ脳部位・細胞種特異的な遺伝子導入法の開発,④オンデマンド超音波遺伝学刺激法によるてんかん発作制御法の開発を実施した.本研究の成果は,オール非侵襲のパイプラインで神経・精神疾患を克服する,革新的医療技術の創出に繋がる可能性がある.Direct control of neural activity by brain stimulation is effective in controlling symptoms of drug-resistant neurological and psychiatric disorders such as intractable epilepsy and depression. However, deep brain stim-ulation and optogenetic stimulation have been invasive due to the need to insert electrodes into the brain. In this study, we aimed to solve the invasiveness problem by developing a new non-invasive brain stimulation technology using ultrasound, which has excellent bio-permeability. To this end, the following studies were conducted: 1) development of in vivo sonogenetic brain stimulation, 2) development of a compact ultra-sound irradiation device, 3) development of a non-invasive, brain region- and cell type-specific gene trans-fection, and 4) control of epileptic seizures by on-demand sonogenetic brain stimulation technology. The re-sults of this research may lead to innovative medical technologies to overcome neurological and psychiatric disorders in an all-noninvasive pipeline.細胞治療は,体外で細胞を加工・培養・評価した後に,機能性細胞を移植することで疾病を治療する新しい医療であるが,細胞を加工するために必要な物質導入技術に制約があるため,治療に用いることの出来る細胞種が限定された.このような課題を解決するため,申請者は,細胞穿刺用金属製ナノチューブという新ナノ材料を開発し,本ナノチューブを細胞に物理的に挿入することで,外来性物質を高効率かつ高生存率で細胞内に届けるナノスタンプ法を開発してきた.本研究課題では,我々が有する新材料

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