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Development of novel gene delivery systems based on the function of biological molecules

Research Project

Project/Area Number 10557234
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 医薬分子機能学
Research InstitutionOsaka University

Principal Investigator

YUTSUDO Masuo (2001)  Research Institute for Microbial Diseases, Osaka University, Associate Professor, 微生物病研究所, 助教授 (70135747)

中西 真人 (1998-2000)  大阪大学, 微生物病研究所, 助教授 (10172355)

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)
Project Period (FY) 1998 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥3,500,000 (Direct Cost: ¥3,500,000)
KeywordsDNA / Nuclear targeting / Phage / Telomere / Cancer / Sendai virus / Fusogenic liposome / Gene therapy / TRF1 / 染色体 / ハイブリッドベクター / ガン胎児抗原 / ナトリウムチャンネル / ラムダファージ / 細胞膜 / 核膜 / Protein Transduction Domain / 人工染色体 / RNAレプリコン / 遺伝子導入 / ベクター
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.

Report

(5 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] M.Nakanishi, et al.: "Gene transfer vectors besed on Sendai virus"J. Cont. Rel.. 54. 61-68 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H.Mizuguchi, et al.: "Tumor Necrosis Factor-a-mediated Tumor Regression by the Direct Delivery of the Genes into the Artery Controlling Tumors In Vivo"Cancer Res.. 58. 5725-5730 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] H.Mizuguchi, et al.: "Fusion of Sendai virus with liposome depends on only F protein, but not HN protein"Virus Res.. 59. 191-201 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Watabe, et al.: "Target Cell Specificity of Fusogenic Liposomes-Membrane Fusion-Mediated Macromolecule Delivery into Human Blood Mononuclear Cells"Biochim. Biophys. Acta. 1416. 339-348 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M.Nakanishi, et al.: "Gene Delivery Systems Using the Sendai Virus"Mol. Memb. Biol.. 16. 123-127 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Nakanishi, et al.: "Positively charged liposomes functions as an efficient immunoadjuvant in inducing cell-mediated immune response to soluble proteins"J. Cont. Rel.. 61. 233-240 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akiko Iahii-Watabe, et al.: "Target Cell Specificity of Fusogenic Liposome-mediated Macromolecule Delivery into Human Blood Cells"Progress in Drug Delivery System. 8. 31-40 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] K.Miyake, et al.: "Transforming growth factor-beta1 stimulates contraction of human glioblastoma cell-mediated collagen lattice through enhanced alpha 2 integrin expression"J. Neuropath. Exp. Neur.. 59. 23-33 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] T.Nakanishi, et al.: "Fusogenic liposomes efficiently deliver expgenous antigen through the cytoplasm into the MHC class I processing pathway"Euro. J. Immun.. 30. 1740-1747 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Eguchi, et al.: "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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M.Horimoto: "A novel strategy for cancer therapy by mutated mammalian degenerin gene transfer"Cancer Gene Ther.. 7. 1341-1347 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] J.Okabe, et al.: "TRF1 is a critical trans-acting factor required for de novo telomere formation in human cells"Hum. Mol. Gen.. 9. 2639-2650 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M.Kondoh, et al.: "Growth inhibition of human leukemia HL-60 cells by an antisense phosphodiester oligonucleotide encapsulated into fusogenic liposomes"Biol. Pharm. Bull.. 23. 1011-1013 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M.Nakanishi, et al.: "Nuclear Targeting of DNA"Euro. J. Pharamaceu. Sci.. 13. 17-24 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Eguchi, et al.: "Protein transduction domain of HIV-1 Tat protein promotes efficient delivery of DNA into mammalian cells"J. Biol. Chem.. 276. 26204-26210 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Q.Li, et al.: "Link of a new type of apoptosis-inducing gene ASY/Nogo-B to human cancer"Oncogene. 20. 3929-3936 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M.Shimakage, et al.: "Expression of Epstein-Barr virus in cutaneous T-cell lymphoma including mycosis fungoides"International Journal of Cancer. 92. 226-231 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 中西真人, 他: "遺伝子治療ハンドブック"株式会社エヌ・ティー・エス. 1085 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 中西真人, 他: "今日のDDS・薬物送達システム"株式会社医薬ジャーナル社. 443 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 中西真人, 他: "バイオ医薬品の品質・安全性評価法"(株)エル・アイ・シー. 504 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsuyoshi Nakanishi, Akira Hayashi, Jun Kunisawa, Yasuo Tsutsumi, Keiichi Tanaka, Yumi Yashiro-Ohtani, <Mahito Nakanishi>_________________-, Hurinu Fujiwara, Toshiyuki Hamaoka and Tadanori Mayumi: "Fusogenic liposomes efficiently deliver expgenous antigen through the cytoplasm into the MHC class I processing parhway"Euro. J. Immun.. 30. 1740-1747 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jun Okabe, Akiko Eguchi, Akinori Masago, Takao Hayakawa and <Mahito Nakanishi>_________________-: "TRF1 is a critical trans-action factor required for de novo telomere formation in human cells"Hum. Mol. Gen.. 9. 2639-2650 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] <Mahito Nakanishi>_________________-, Teruo Akuta, Emi Nagoshi, Akiko Eguchi, Hiroyuki Mizuguchi and Takao Senda: "Nuclear Targeting of DNA."Euro. J. Pharamaceu. Sci.. 13. 17-24 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akiko Eguchi, Teruo Akuta, Hajime Okuyama, Takao Senda, Haruhiko Yokoi, Hachiro Inokuchi, shigeo Fujita, Takao Hayakawa, Katsuo Takeda, Mamoru Hasegawa and <Mahito Nakanishi>_________________-: "Protein transduction domain of HIV-1 Tat protein promotes effieceint delivery of DNA into mammalian cells"J. Biol. Chem.. 276. 26204-26210 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Q. Li, B. Qi. M. Shimakage, K. Oka, N. Yoshioka, K. Kodama, H. Inoue, A. Hakura, E. J. Stanbridge and <M Yatsudo>__________-: "Link of a new type of apoptosis-inducing gene ASY/Nogo-B to human cancer"Oncogene. 20. 3929-3936 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] M. Shimakage, T. Sasagawa, K. Kawahara, <M. Yutsudo>_________-, H. Kusuoka, and T. Kozuka: "Expression of Epstein-Barr virus in cutaneous T-cell lymphoma including mycosis fungoides"Int. J. Cancer. 92. 226-231 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] A.Eguchi, 他: "Protein transduction domain of HIV-1 Tat protein promotes efficient delivery of DNA into mammalian cells"The Journal of Biological Chemistry. 276. 26204-26210 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Nakanishi, 他: "Nuclear Targeting of DNA"European Journal of Pharmaceutical Sciences. 13. 17-24 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Q.Li, 他: "Link of a new type of apoptosis-inducing gene ASY/Nogo-B to human cancer"Oncogene. 20. 3929-3936 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Shimakage, 他: "Expression of Epstein-Barr virus in cutaneous T-cell lymphoma including mycosis fungoides"International Journal of Cancer. 92. 226-231 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Jun Okabe, et al.: "TRF1 is a critical trans-acting factor required for de novo telomere formation in human cells"Human Molecular Genetics. 9. 2639-2650 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akiko Eguchi, et al.: "Characterization of Cell Lines with a Defect in a Post-Adsorption Stage of Sendai Virus-Mediated Membrane Fusion"The Journal of Biological Chemistry. 275. 17549-17555 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masayoshi Horimoto, et al.: "A novel strategy for cancer therapy by mutated mammalian degenerin gene transfer"Cancer Gene Therapy. 7. 1341-1347 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Keisuke Miyake, et al.: "Transforming growth factor-beta1 stimulates contraction of human glioblastoma cell-mediated collagen lattice through enhanced alpha 2 integrin expression"Journal of Neuropathology and Experimental Neurology. 59. 23-33 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsuyoshi Nakanishi, et al.: "Fusogenic liposomes efficiently deliver expgenous antigen through the cytoplasm into the MHC class I processing pathway"European Journal of Immunology. 30. 1740-1747 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mahito Nakanishi, et al.: "Nuclear Targeting of DNA"European Journal of Pharamaceutical Science. (印刷中).

    • Related Report
      2000 Annual Research Report
  • [Publications] Mizuguchi,H.,et al.: "Fusion of Sendai virus with liposome depends on only F protein,but not HN protein"Virus Res.. 59. 191-201 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Watanabe,A.,et al.: "Target Cell Specificity of Fusogenic Liposome-Membrane Fusion-MediatedMacromolecule Delivery into Human Blood Mononuclear Cells"Biochem. Biophys. Acta. 1416. 339-348 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakanishi,M.,et al.: "Gene Delivery Systems Using the Sendai Virus"Mol. Memb. Biol.. 16. 123-127 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakanishi,M.,et al.: "Positively charged liposomes functions as an efficient immunoadjuvant in inducing cell-mediated immune response to soluble proteins"Journal of Controlled Release. 61. 233-240 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyake,K. et al.: "Transforming growth factor-beta 1 stimulates contraction of human glioblastoma cell-mediated collagen lattice through enhanced alpha 2 integrin expression"Journal of Neuropathology and Experimental Neurology. 59. 23-33 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakanishi,M.,et al.: "Nuclear Targeting of DNA"European Journal of Pharmaceutical Science. (印刷中).

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakanishi,M.,et al.: "Gene transfer vectors besed on Sendai virus" Journal of Controlled Release. 54. 61-68 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyake,K.,et al.: "Transforming growth factor-beta1 stimulates contraction of human glioblastoma cell-mediated collagen lattice through enhanced alpha 2 integrin expression" Journal of Experimental Therapeutics and Oncology. (印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] Nakanishi,M.,et al.: "Gene Delivery Systems Using the Sendai Virus" Molecular Membrane Biology. (印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] Mizuguchi,H.,et al.: "Tumor Necrosis Factor-a-mediated Tumor Regression by the Direct Delivery of the Genes into the Artery Controlling Tumors In Vivo" Cancer Reserach. (印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] Watabe,A.,et al.: "Target Cell Specificity of Fusogenic Liposomes-Membrane Fusion-Mediated Macromolecule Delivery into Human Blood Mononuclear Cells" Biochimica et Biophysica Acta. (印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] Mizuguchi,H.,et al.: "Fusion of Sendai virus with liposome depends on only F protein,but not HN protein" Virus Research. (印刷中).

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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