Development of non-toxic herpes simplex virus vectors for neural-specific gene delivery
| Project/Area Number |
16K08249
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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 |
Biological pharmacy
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
内田 宏昭 東京大学, 医科学研究所, 特任准教授 (20401250)
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| Research Collaborator |
Glorioso Joseph C., III
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ヘルペスウイルス / 遺伝子治療 / 遺伝子発現 / インシュレーター / 無毒化 / 神経特異的 / 神経特異的遺伝子発現 / 神経細胞特異的遺伝子発現 / UL41 / ウィルス / ゲノム / 脳・神経 / 薬学 / 発現制御 |
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| Outline of Final Research Achievements |
We aimed to generate an innovative non-toxic herpes simplex virus (HSV) -based vector capable of neuro-specific delivery of therapeutic genes. Here, we demonstrated that chromatin insulator-like elements in the terminal repeat (TR) locus of non-toxic HSV viral genome play a crucial role in the transcription from the TR locus in neural cells. In addition, the modification of the chromatin insulator-like elements significantly improves the transgene expression from the TR locus. Our results would provide the sophisticated neural-specific gene transduction system with non-toxic HSV vector.
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| Academic Significance and Societal Importance of the Research Achievements |
現在のウイルス製剤開発において最重要課題のひとつは標的組織特異的治療遺伝子の送達である。多くのウイルスベクターでは非特異的な遺伝子導入の抑制が不完全であり、未だ高精度な標的化遺伝子導入システムは存在しない。一方、我々は既にHSV糖タンパク質gD改変（細胞侵入を制御）及びにmiRNA認識配列（翻訳を制御）の利用による非特異的遺伝子導入抑制技術を確立している。これに本研究で着目するTR制御配列による標的細胞特異的転写制御技術（転写を制御）を融合すれば、極めて高精度な細胞標的化が可能となる。従って本研究成果は神経疾患に対するウイルス製剤を開発する上で理想的なプラットフォームを提供すると考えられる。
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] Syncytial Mutations Do Not Impair the Specificity of Entry and Spread of a Glycoprotein D Receptor-Retargeted Herpes Simplex Virus.2016
Author(s)
Okubo Y, Uchida H, Wakata A, Suzuki T, Shibata T, Ikeda H, Yamaguchi M, Cohen JB, Glorioso JC, Tagaya M, Hamada H, Tahara H.
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Journal Title
J Virol.
Volume: Nov28;90(24)
Issue: 24
Pages: 11096-11105
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Development of an oncolytic HSV vector fully retargeted specifically to cellular EpCAM for virus entry and cell-to-cell spread.2016
Author(s)
Shibata T, Uchida H, Shiroyama T, Okubo Y, Suzuki T, Ikeda H, Yamaguchi M, Miyagawa Y, Fukuhara T, Cohen JB, Glorioso JC, Watabe T, Hamada H, Tahara H.
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Journal Title
Gene Therapy.
Volume: 印刷中
Issue: 6
Pages: 479-488
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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