| Project/Area Number |
16K08042
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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 |
Veterinary medical science
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| Research Institution | National Institute of Infectious Diseases |
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Principal Investigator |
Kaku Yoshihiro 国立感染症研究所, 獣医科学部, 主任研究官 (70392321)
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| Co-Investigator(Kenkyū-buntansha) |
浅井 知浩 静岡県立大学, 薬学部, 教授 (00381731)
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| Project Period (FY) |
2016-04-01 – 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 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | scFv / 狂犬病 / ナノ粒子 / DDS / 経鼻接種 / 治療 / 狂犬病ウイルス / intrabody / ピンポイントDDS / 小型抗体 |
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| Outline of Final Research Achievements |
We developed novel nanoparticles aiming to efficiently deliver a gene expressing a small artificial antibody molecule (single chain variable fragment; scFv), scFv-P19, which showed an inhibitory effect on the growth of rabies virus (RABV), to nervous tissue. By conducting epitope mapping of scFv-P19, we were able to narrow down the range of epitope of scFv-P19 to 6 amino acid residues near the N-terminus of RABV-P protein. In addition, in order to measure the RABV growth inhibitory effect of scFv having low expression efficiency, we developed a method of selecting only scFv/GFP-expressing cells from the cells transfected with the scFv/GFP co-expression vector using flow cytometry, to be subjected to measure the RABV growth inhibitory effect of scFvs.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、ナノ粒子を用いて抗RABV人工小型抗体遺伝子を神経組織へ効率的に送達するための技術基盤が整備された。また、RABVの増殖阻害効果を示す人工小型抗体のエピトープが特定されたことや、発現効率の低い小型抗体のRABV増殖阻害効果の測定系が構築されたことにより、小型抗体を利用した狂犬病の治療法開発に向けた展望が開けた。
ナノ粒子による遺伝子の神経組織への送達は、アルツハイマー病、パーキンソン病といった難治性神経疾患についても、応用が期待される。
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