Re-engineering of AAV particle by "peptide insertion" method
Project/Area Number |
18K19298
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
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Research Institution | Osaka University |
Principal Investigator |
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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: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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Keywords | アデノ随伴ウイルス / 環状ペプチド / ターゲッティング / 遺伝子治療 / ペプチドタグ / 構造生物学 / 遺伝子導入 |
Outline of Final Research Achievements |
In this study, we aimed at changing the cellular tropism of adeno-associated virus (AAV), one of the most promising vector for gene therapy. Although AAV can infect many cell types, the infection efficiency is not high enough to warrant its broad application in gene therapy. The broad tropism can also be a problem where gene delivery needs to be restricted to a specific organ/tissue. In order to achieve greater control of AAV's cellular infectivity, we chose “peptide grafting” method to grant AAV capsid to bind to a specific receptor and infect limited type of cells for gene delivery. We first sought for loop positions that allow peptide insertion, and identified 2 candidate sites. Then an artificial peptide sequence derived from a macrocyclic peptide known to bind to Plexin B1 was inserted in these positions. We confirmed that the modified virus was able to infect cells expressing Plexin B1 but not the parent cells, indicating the general applicability of this approach.
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Academic Significance and Societal Importance of the Research Achievements |
遺伝子治療は、先天性遺伝子疾患をゲノムレベルで「治療」してしまう夢の技術であるが、様々な課題のためにまだ実現に至っていない。アデノ随伴ウイルス(AAV)は遺伝子治療における最も有望なベクターだが、そのトロピズム(細胞指向性)を随意にコントロールすることが出来ていない。本研究によって、AAVのキャプシドに標的結合能をもつヘアピンペプチドを提示させることによって、特定の受容体を発現する細胞だけに感染し遺伝子発現を誘導できることを示した。つまり、筋肉、肝臓、網膜、などの臓器だけに目的の遺伝子を届ける道が開けたと言える。
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Report
(3 results)
Research Products
(30 results)
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[Journal Article] Structural basis of sarco/endoplasmic reticulum Ca2+-ATPase 2b regulation via transmembrane helix interplay2019
Author(s)
Michio Inoue, Nanami Sakuta, Satoshi Watanabe, Yuxia Zhang, Kunihito Yoshikaie, Yoshiki Tanaka, Ryo Ushioda, Yukinari Kato, Junichi Takagi, Tomoya Tsukazaki, Kazuhiro Nagata, Kenji Inaba
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Journal Title
Cell Reports
Volume: 27
Issue: 4
Pages: 1221-1230
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Macrocyclic peptide-based inhibition and imaging of hepatocyte growth factor.2019
Author(s)
Sakai K, Passioura T, Sato H, Ito K, Furuhashi H, Umitsu M, Takagi J, Kato Y, Mukai H, Warashina S, Zouda M, Watanabe Y, Yano S, Shibata M, Suga H, Matsumoto K
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Journal Title
Nature Chemical Biology
Volume: 15
Issue: 6
Pages: 598-606
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Distinct Localization of Mature HGF from its Precursor Form in Developing and Repairing the Stomach.2019
Author(s)
Jangphattananont N, Sato H, Imamura R, Sakai K, Terakado Y, Murakami K, Barker N, Oshima H, Oshima M, Takagi J, Kato Y, Yano S, Matsumoto K
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Journal Title
International Journal of Molecular Sciences
Volume: 12
Issue: 12
Pages: 2955-2955
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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