2001 Fiscal Year Final Research Report Summary
Development of novel gene delivery systems based on the function of biological molecules
| Project/Area Number |
10557234
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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 | 展開研究 |
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| Research Field |
医薬分子機能学
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| Research Institution | Osaka University |
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Principal Investigator |
YUTSUDO Masuo Research Institute for Microbial Diseases, Osaka University, Associate Professor, 微生物病研究所, 助教授 (70135747)
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| Co-Investigator(Kenkyū-buntansha) |
HASEGAWA Mamoru DNAVEC Research Inc., Director, 所長(研究職)
NAKANISHI Mahito National Institute for Advanced Industrial Sciences and Technology, Principal Investigator, ジーンディスカバリー研究センター, 主任研究員 (10172355)
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| Project Period (FY) |
1998 – 2001
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| Keywords | DNA / Nuclear targeting / Phage / Telomere / Cancer / Sendai virus / Fusogenic liposome / Gene therapy |
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| Research Abstract |
In this research project, we investigate the essential function of biological systems, such as viruses and chromosomes, which will be useful for developing novel non-viral devices for gene transfer and expression. The results we have obtained during the term of this project are summarized as below.
1. We analyzed the mechanism of membrane fusion that will mediated efficient DNA delivery, and found that the membrane fusion requires essential non-receptor molecules which may be interacted with HN protein of Sendai virus.
2. We establish the system to display various biological peptides on the surface of lambda phage particles, and propose to use this system to analyze the function of these peptides as components of non-viral gene delivery vehicles. Using this system, we showed that Tat peptide could enhance the delivery of lambda phage DNA into the cells and that NLS signal peptide of SV40 T antigen could target the lambda phage particles into the nucleus through the nuclear pore complex.
3. We analyze the mechanism by which human chromosomes are stabilized in the nucleus, and found that the interaction between TRF1 and telomere repeat was involved in this process.
4. We succeeded to cure mice with the disseminated cancer by treating them with the fusogenic liposomes encapsulating cancer-specific suicide gene.
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[Publications] Akiko Eguchi, Toru Kondoh, Hirokazu Kosaka, Takashi Suzuki, Hiroshi Momota, Akinori Masago, Tetsuya Yoshida, Hideharu Taira, Akiko Ishii-Watabe, Jun Okabe, Jianhong Hu, Naoyuki Miura, Shigeharu Ueda, Yasuo Suzuki, Takao Taki, Hayakawa and <Mahito Nakanishi>___________________^-: "Identification and CHaracterization of Cell Lines with a Defect in a Post-Adsorption Stage of Sendai Virus-Mediated Membrane Fusion"J. Biol. Chem.. 275. 17549-17555 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Masayoshi Horimoto, Yutaka Sasaki, Shinya Ugawa, Shigeo Wada, Takashi Toyama, Kenya Iyoda, Yuki Minami, Toshifumi Ito, Akiko Eguchi, <Mahito Nakanishi>_________________-,Shoichi Shimada, Masay Tohyama, Norio Hayashi and Masatsugu Hori: "A novel strategy for cancer therapy by mutated mammalian degenerin gene transfer"Cancer Gene Ther.. 7. 1341-1347 (2000)
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[Publications] Kondoh, M., Matsuyama, T., Suzuki, R., Mizuguchi, H., Nakanishi, T., Nakagawa, S., Tsutsumi, Y., Nakanishi, M., Sato, M. and Mayumi, T.: "Growth inhibition of human leukemia HL-60 cells by an antisense phosphodiester okihonucleotide encapsulated into fusogenic liposomes"Biol. Pham. Bull.. 23. 1011-1013 (2000)
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