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A novel Drug Delivery System Using HBV Envelop Protein Particles

Research Project

Project/Area Number 13470243
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionKeio University

Principal Investigator

UEDA Masakazu  Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (50142419)

Co-Investigator(Kenkyū-buntansha) MATSUURA Yoshifumi  Keio university, School of Medicine, Assistant, 医学部, 助手 (90317157)
HASEGAWA Hirotoshi  Keio university, School of Medicine, Instructor, 医学部, 助手 (00218455)
JINNO Hiromitsu  Keio university, School of Medicine, Instructor, 医学部, 助手 (20216261)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 2002: ¥4,800,000 (Direct Cost: ¥4,800,000)
Keywordsgene therapy / Missile therapy / L particle / hepatocellular carcinoma / GFP-expression plasmid / ヌードラット / ヒト肝細胞癌 / ヒト幹細胞 / ヌードマウス / 肝細胞癌 / 緑色螢光遺伝子
Research Abstract

There are many hepatopathies that may be candidates for gene therapy. Gene therapy needs a vector that is carried together with its genes into a target cell or organ. Desirable vectors should be extremely safe, have good transfection efficiency, and demonstrate a high specificity for their target. In 1992, Kuroda et al. reported on the large amount of HBsAg envelope L particles that could be synthesized in yeast cells. HBV envelope L particles overproduced by yeast are hollow nanoparticles(average diameter 80nm) displaying the pre-S1 peptide indispensable for human liver-specific infection. Either a GFP(green fluorescence protein)-expression plasmid or a fluorescent dye(calcein) was incorporated into L particles by electroporation, and directly used for the transfection of various cells in vitro. Either GFP- or calcein-derived fluorescence was observed only in human liver-derived cells such as NuE and HepG2 not but WiDr and A431. We transplanted human hepatocellular carcinoma cells and human colon cancer cells subcutaneously in nude rats or nude mice. L particles with. GFP-expression plasmide or carcein were infected into the tumor-bearing nude rats or mice through tail vein. After 7 days, fluorescence was observed specifically in the subcutaneous heptocellular carcinoma, but not was observed in the subcutaneous colon cancer, brain, heart, lung, liver, spleen, kidney, adrenal gland, intestine, or muscle of rats or mice. When the human clotting factor IX gene, a therapeutic gene for hemophilia B, was transferred into the xenograft model by the L particles, therapeutic factor IX levels were obtained in the plasma for at least 1 month. In conclusion, HBsAg L particles showed a specific recognition ability for human-derived liver tissue and demonstrated a transgenie ability in an in vivo system.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Yamada T., et al.: "Novel gene and drug delivery system specific to human hepatocyte Using HBV-derived emnty nanonarticles"Nature Biotechnology. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Jinno H., et al.: "The cytotoxicity of a conjugated composed of human epidermal growth factor and eosinophil cationic protein"Anteicancer Res.. 22. 4141-4146 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasui K., et al.: "TFDP1.CDL4A, CDC16 identified as targets for amplification at 13q14 in Hepatocellular carcinomas"Hepatology. 35. 1476-1484 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Morise Z., et al.: "Reactive oxygen species and vascular cell adhesion molecular-1 in distant organ failure following bile duct obstruction in mice"Digestive Diseases and Sciences. 47. 607-613 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamura Y., et al.: "Immunosuppressive and anticancer effect of a mammalian RNA targeting heigh-affinity IL-2 receptors"Eur J Surgery. 168. 49-54 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maeda T., et al.: "Growth inhibition of mammalian cells by eosinophil cationic protein"Eur J Biochem. 269. 307-316 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamada Y., Iwasaki Y., Tada H., Iwabuki H., Chuah M.K.L., VandenDriessche T., Kondo A., Ueda M., Seno M., Tanizawa K, Kuroda S.: "Novel gene and drug delivery system specific to human hepatocyte using hepatitis B virus-derived empty nanoparticles"Nature Biotechnology. In press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Jinno H., Ueda M., 0zawa S. Ikeda T, Kitajima M., Maeda T., Seno M.: "The cytotoxicity of a conjugate composed of human epidermal growth factor and eosinophil cationic protein"Anticancer Res.. 22. 4141-4146 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yasui K., Arii S., Zhao C., Imoto I., Ueda M., Nagai H., Emi M., Inazawa J.: "TFDP1, CUL4A, and CDC16 identified as targets for amplification at 13q34 in hepatocellular carcinomas"Hepatology. 35. 1476-1484 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Morise Z., Ueda M., Kitajima M., Epistein J.C., Granger D.N., Grisham M.B.: "Reactive oxygen species and vascular cell adhesion molecular-1 in distant organ failure following bile duct obstruction in mice"Degestive Deseases and Sciences. 47. 607-613 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamura T., Ueda M., Psarras K, Suwa T., Watanabe Y, Kameyama N., Tanabe M., Imamura H., Kitajima M: "Immunosuppressive and anticancer effect of a mammalian ribonuclease targeting high.- affinity interluekin-2 receptors"Eur J surgery. 168. 49-54 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Maeda T., Kitazoe M., Tada, H., Liorens. R., Saomon, D.S., Ueda M., Yamada H., Seno M: "Growth inhibition of mammalian cells by eosinophil cationic protein"Eur.J.Biochem.. 269. 307-316 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hiromitsu Jinno: "The cytotoxicity of a conjugate composed of human EGF and eosinophil cationaic protein"Anticancer Res. 22. 4141-4146 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kohichiroh Yasui: "TFDP-1, CUL4A, and CDC16 identified as targets for amplification at 13q34 in hepathocellular carcinoma"Hepatology. 35. 1476-1484 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tadashi Yamamura: "Immunosuppressive and anticancer effect of a mammalian ribonuclease that targets high-affinity IL-2 receptor"Eur J Surgery. 168. 49-54 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takashi Maeda: "Growth inhibition of mammalian cells by eosinophil cationic"Eur J Biochem.. 269. 307-316 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Morise Z, et al.: "Reactive oygln species and vascular celladhesion moleaclar-1 in clistant organ frilure following hile duct obstruction in mice"Digestive Deseases and Sciences. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimizu S, et al.: "Detection of IL-2 receptor gene expression in peripheral blood of renal transplant patients"Surgery Today. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamura T, et al.: "Immunosuppresire and anticancer effect of a mammalian ribonuclease targeting high-affinity interleukin-2 receptors"Eur J Surgery. (in press).

    • Related Report
      2001 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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