Project/Area Number |
17K19461
|
Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
Allocation Type | Multi-year Fund |
Research Field |
Neuroscience and related fields
|
Research Institution | Fukushima Medical University |
Principal Investigator |
|
Research Collaborator |
Takeuchi Kosei
Kato Shigeki
Fukabori Ryoji
|
Project Period (FY) |
2017-06-30 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
|
Keywords | 逆行性遺伝子導入 / ウィルスベクター / 受容体 / ノックアウトマウス / 結合タンパク質 |
Outline of Final Research Achievements |
Highly efficient retrograde gene transfer vector is a pseudotype of lentiviral vectors with fusion envelope glycoproteins composed of segments from rabies virus and vesicular stomatitis virus glycoproteins. Although this vector system is useful for the functional analysis of the complex brain network, the mechanisms underlying vector entry into nerve terminal regions is unknown. In the present study, we tried to identify the receptors for the vector. The intracranial injection experiment into the brains of some knockout mice for the candidate molecules excluded the possibility that these candidate molecules or metabolites are the receptors. In contrast the injection experiments with some inhibitors for sugar chains suggested the possibility that sialic acids may be involved in the binding of the vector on cell surface.
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Academic Significance and Societal Importance of the Research Achievements |
本研究により、これまで実体の不明であった、RVに関連するベクター系受容体にはシアル酸を持つ糖鎖が関与する可能性が示唆された。本受容体の解明は、神経科学研究に重要な高頻度逆行性遺伝子導入ベクターの神経終末への結合および取り込みの機構を明らかにすることに繋がり、これらのベクターの導入効率を向上させるための有益な情報を提供すると考えられる。また、実際の狂犬病ウィルスの受容体である可能性もあり、本ウィルスの感染を防御あるいは軽減するための臨床応用にも結び付く可能性がある。
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