2021 Fiscal Year Final Research Report
Botulinum neurotoxin-based drug delivery systems for targeting neurons
| Project/Area Number |
20K22722
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0801:Pharmaceutical sciences and related fields
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| Research Institution | Tokyo University of Agriculture |
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Principal Investigator |
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| Project Period (FY) |
2020-09-11 – 2022-03-31
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| Keywords | ボツリヌス神経毒素 / DDS / ペプチド製剤 / α-シヌクレイン / ボツリヌス中毒 |
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| Outline of Final Research Achievements |
Peptides and antibodies for targeting intracellular proteins have been developed. However, the effective delivery of it into the targeted cells remains challenging. Here, I have developed a detoxified-BoNT for targeted synaptotagmin-expressed neurons. The VHH fused to the new detoxified-BoNT was delivered into neurons with compatible efficacy with previously reported detoxified-BoNT for SV2-expressed cells. Furthermore, the degeneration efficacy of the peptides for aggregated proteins involved with Parkinson's disease was evaluated using the cultured cell model.
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| Free Research Field |
細菌学
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| Academic Significance and Societal Importance of the Research Achievements |
アルツハイマー病に代表される神経変性疾患は高齢化社会における課題である。本研究では、神経細胞内の病原タンパク質の分解を目的として、無毒化したボツリヌス神経毒素（BoNT）を薬物キャリアーとした新規薬物送達システムの構築を行った。本研究において、B型 BoNT の受容体結合ドメインを含む新規の無毒化 BoNT を開発し、ペプチドあるいは抗体送達活性を検証した。本成果は、神経細胞変性を引き起こす病原タンパク質を標的とした新規治療法の開発に寄与すると期待される。
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