| Project/Area Number |
18K19599
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 56:Surgery related to the biological and sensory functions and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
栗田 昌和 東京大学, 医学部附属病院, 助教 (20424111)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2018: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
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| Keywords | 血管奇形 / 遺伝子治療 / ゲノム編集 / 動物モデル / 遺伝子導入 / アデノ随伴ウイルスベクター / 血管腫 / 体性突然変異 / モザイク変異 |
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| Outline of Final Research Achievements |
An inducible genome editing system, composed of multiple LoxP sequences, cis-Cre recombinase, and CRISPR/Cas9 sequences was constructed on C57BL/6 wildtype mouse Rosa26 locus cloned on pUC19 vector for the development of soft tissue vascular malformation animal models. In order to make a new Adenovirus Associated Vector (AAV) capsid optimized for the gene delivery to murine endothelial cells in vivo, transduction efficiency of 9 known AAV serotypes was assessed in a new in vitro tissue transduction model. For the AAV5, a best backbone capsid selected by our analysis, revised peptide display capsid was prepared for the future directed evolution.
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| Academic Significance and Societal Importance of the Research Achievements |
体表・軟部組織の血管奇形は、従来、血管腫として呼ばれていた疾患群であり、特に広範な病変を有する症例においては整容的、機能的障害に加えて疼痛、出血などの症状を呈することから終生にわたって、外科的治療や血管内治療を繰り返す必要があり、既存の治療には限界がある。本研究によって開発した技術は、実際の症例に即した動物モデルを作成し、変異を有する病変内のゲノムを修復する、新しい治療開発を進める礎となる。
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