Elucidation of cytotoxicity mechanism for oncolytic virus by genome-editing high-throughput knockout
Project/Area Number |
19K16500
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 48030:Pharmacology-related
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Research Institution | Jikei University School of Medicine (2022) The University of Tokyo (2019, 2021) |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | ウイルス療法 / ゲノム編集 |
Outline of Research at the Start |
本研究では、遺伝子を自由に改変できるゲノム編集という技術を用いて幅広い遺伝子を欠失させた癌細胞集団を作成する。様々な遺伝子を欠失させた癌細胞集団を用いて、腫瘍溶解性ウイルスであるコクサッキーウイルスB群3型(CVB3)の細胞傷害性及び抗腫瘍免疫誘導に必要な遺伝子を同定する。CVB3の癌細胞殺傷メカニズムを詳細に理解し、ウイルス感染に必要な受容体の発現のみならず、CVB3の殺細胞効果や抗腫瘍免疫誘導に必要な遺伝子を把握することで、治療される患者様の適応基準を科学的に設定することが可能となる。
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Outline of Final Research Achievements |
In this study, we developed cancer cell line populations in which various genes were deleted by genome editing technology and identified genes required for cytotoxicity of an oncolytic virus, coxsackievirus group B type 3 (CVB3), using them. used the cancer cell populations to generate coxsackievirus group B type 3, an oncolytic virus. By understanding the cytotoxicity mechanism of CVB3 in detail, it becomes possible to scientifically set adaptation criteria. In this time, we analyzed the results of next-generation sequencing, identified the barcode sequence integrated into the lentivirus, and successfully identified various gene candidates of CVB3 cytotoxicity.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、これまでにCVB3の細胞傷害性に関して報告のない遺伝子が多く見つかっており、さらに報告のないシグナル経路がウイルス増殖に関連している可能性が示唆され、今後のウイルス療法開発に重要な鍵となることが予想される。 また、本研究で同定された遺伝子が他のエンテロウイルスに関与しているかどうか解析することにより、他のエンテロウイルスに対する治療薬の開発に繋がる可能性がある。
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Report
(3 results)
Research Products
(22 results)
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[Journal Article] Extremely low organ toxicity and strong antitumor activity of miR-34-regulated oncolytic coxsackievirus B3.2019
Author(s)
Jia, Y., Miyamoto, S., Soda, Y., Takishima, Y., Sagara, M., Liao, J., Hirose-Yotsuya, L., Hijikata, Y., Miura, Y., Hara, K., Iwanaga, A., Ota, Y., Tani, K.
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Journal Title
Mol Ther Oncolytics.
Volume: 12
Pages: 246-258
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] KLF1 Mutation E325K Induces Cell-cycle Arrest in Erythroid Cells Differentiated from Congenital Dyserythropoietic Anemia (CDA) Patient-specific Induced Pluripotent Stem Cells.2019
Author(s)
Kohara H, Utsugisawa T, Sakamoto C, Hirose L, Ogawa Y, Ogura H, Sugawara A, Aoki T, Iwasaki T, Asai T, Doisaki S, Okuno Y, Muramatsu H, Abe T, Kurita R, Miyamoto S, Sakuma T, Shiba M, Yamamoto T, Ohga S, Yoshida K, Ogawa S, Ito E, Kojima S, Kanno H, Tani K.
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Journal Title
Exp Hematol.
Volume: 73
Pages: 25-37
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Analysis of Human iPSCs Generated by a Non-Integrating Measles Virus Vector.2019
Author(s)
Liao J, Soda Y, Sugawara A, Miura Y, Hiramoto T, Tahara M, Takishima Y, Hijikata Y, Miyamoto S, Takeda M, Tani K.
Organizer
American Society of Gene and Cell Therapy 22nd Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Direct induction of naive-like human induced pluripotent stem cells (iPSCs) by a non-integrating measles virus vector.2019
Author(s)
Liao J, Soda Y, Sugawara A, Miura Y, Hiramoto T, Tahara M, Takishima Y, Hijikata Y, Miyamoto S, Takeda M, Tani K.
Organizer
第25回日本遺伝子細胞治療学会学術集会
Related Report
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[Presentation] Measles virus vector is a promising tool for T-cell engineering and establishing naive-like iPSCs.2019
Author(s)
Liao J, Soda Y, Sugawara A, Miura Y, Hiramoto T, Tahara M, Takishima Y, Miyamoto S, Hijikata Y, Takeda M, Tani K.
Organizer
第81回日本血液学会学術集会
Related Report
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[Presentation] Pilot study to detect circulating tumor cells in human peripheral blood using 5-aminolevulinic acid.2019
Author(s)
Hirose L, Kohara H, Sagara M, Miura Y, Hijikata Y, Soda Y, Miyamoto S, Takahashi S, Shinozaki M, Denda T, Tanaka Y, Ota Y, Watanabe E, Tanaka T, Nakajima M, Kiniwa S, Okuyama R, Fukuhara H, Inoue K, Namikawa T, Hanazaki K, Tani K.
Organizer
第81回日本血液学会学術集会
Related Report
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