Construction of nanocapsule targeting mutated mitochondria for gene therapy
| Project/Area Number |
17H02094
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Hokkaido University |
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Principal Investigator |
Yamada Yuma 北海道大学, 薬学研究院, 准教授 (60451431)
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| Co-Investigator(Kenkyū-buntansha) |
田村 篤志 東京医科歯科大学, 生体材料工学研究所, 准教授 (80631150)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | 薬物送達システム / ミトコンドリア / 薬物送達 |
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| Outline of Final Research Achievements |
In this study, we validated a mitochondrial gene therapeutic strategy using fibroblasts from a mitochondrial disease patient by the mitochondrial delivery of therapeutic nucleic acids. The treatment involved the use of a liposome-based carrier (a MITO-Porter) for delivering therapeutic nucleic acids to mitochondria via membrane fusion. The results confirmed that the mitochondrial transfection of therapeutic nucleic acids by the MITO-Porter system resulted in a decrease in the levels of mutated mitochondria of diseased cells. An evaluation of mitochondrial respiratory activity by respirometry also showed that transfection using the MITO-Porter resulted in an increase in maximal mitochondrial respiratory activity in the diseased cells. These results support the conclusion that the mitochondrial delivery of therapeutic nucleic acids represents a viable strategy for mitochondrial gene therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
難病指定されているミトコンドリア病などミトコンドリア機能異常が関連する疾患の多くはミトコンドリア遺伝子の変異・欠損が原因であることが報告さているが、現在の治療法はビタミン剤などを継続的に投与し、ミトコンドリア機能を一時的に補助する対症療法が主流である。本研究では、ミトコンドリア標的型ナノカプセル【MITO-Porter】を用いて、患者由来細胞に治療用核酸を送達する「ミトコンドリアを標的とした遺伝治療戦略」の実証に成功した。ミトコンドリアを標的とした遺伝子治療は、これまでの治療法に代わる難病の根本治療につながるため医療に大きなインパクトを与える。
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Report
(4 results)
Research Products
(64 results)
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[Journal Article] Validation of gene therapy for mutant mitochondria by delivering mitochondrial RNA using a MITO-Porter, a liposome-based nano device2020
Author(s)
Kawamura E, Maruyama M, Abe J, Sudo A, Takeda A, Takada S, Yokota T, Kinugawa S, Harashima H, Yamada Y
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Journal Title
Mol. Ther. - Nucleic Acids
Volume: -
Pages: 687-698
DOI
Related Report
Peer Reviewed / Open Access
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