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Development of gene transfer by in vivo electroporation to the vascular wall

Research Project

Project/Area Number 14571126
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionThe University of Tokyo

Principal Investigator

MIYATA Tetsuro  The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (70190791)

Co-Investigator(Kenkyū-buntansha) HAMADA Hirofumi  Sapporo Medical University, Dept. of Molecular Medicine, Professor, 分子医学研究部門, 教授 (00189614)
SAKUMA Ichiro  The University of Tokyo, Graduate school and faculty of engineering, Professor, 大学院・新領域創成科学研究科, 教授 (50178597)
SHIGEMATSU Hiroshi  The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (40134556)
SHIGEMATSU Kunihiro  The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (20215966)
KOYAMA Hiroyuki  The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 助教授 (10241994)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywordselectroporation / plasmid DNA / gene transfer
Research Abstract

We developed a nonviral method for arterial gene transfer by in vivo electroporation with plasmid DNA. Electroporation is the physical process of including nanometreaized transient pores in a cell membrane by the application of short duration, high intensity electric field pulses to cells or tissues. The most important parameters for effective electroporation are: the stimulation voltage, the pulse duration, the electric current, plasmid concentration, and the shape of an electrode.
Result: Electroporation with 30 voltage and pulse duration of 20 msec resulted in a marked increase of gene expression in vessel wall. The concentration of 400μ g/ml plasmid DNA is most optimal. The Bite of the vessel gene-transferred by in vivo electroporation is focused around the edge of the electrode. The same findings are demonstrated by the simulation model of vessel wall and the experiment of optical mapping. We compare with gene expression in vessel wall between with the monoplate electrode, which is one 5^*1mm plate, and the multiplate electrode, which is two plates in parallel. The gene expression using muitiplate electrode is superior to the one of monoplate electrode.
In summary, we developed a method for gene transfer using electroporation, an approach which proved to the safe and more efficient than that using naked DNA. And then it will be possible that the site or the mount of gene expression is handled in the future.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Inoue S, Koyama H, Miyata T, Shigematsu H: "Cell replication induces in-stent lesion growth in a rabbit carotid artery with preexisting intimal hyperplasia."Atherosclerosis. 162. 345-353 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Inoue S, Koyama H, Miyata T, Shigematsu H: "Pathogenetic heterogeneity of in-stent lesion formation in human peripheral arterial disease."Journal of Vascular Surgery. 35. 672-678 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyata T, Sato O, Koyama H, Shigematsu H, Tada Y.: "Long-term survival after surgical treatment of patients with Takayasu's arteritis."Circulation. 108. 1474-1480 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishikage S, Koyama Y, Miyata T, Shigematsu H.: "In vivo electroporation enhances plasmid-based gene transfer of basic fibroblast growth factor for the treatment of ischemic limb."Journal of Surgical Research. (in press). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 宮田哲郎, 小山博之: "血管の再生医療"呼吸と循環. 50巻4号. 377-383 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Inoue S, Koyama H, Miyata T, Shigematsu H: "Cell replication induces in-stent lesion growth in a rabbit carotid artery with preexisting intinial hyperplasia."Atherosclerosis. 162. 345-353 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Inoue S, Koyama H, Miyata T, Shigematsu H: "Pathogenetic heterogeneity of in-stent lesion formation in human peripheral arterial disease."Journal of Vascular Surgery. 35. 672-678

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyata T, Sato O, Koyama H, Shigematsu H, Tada Y.: "Long-term survival after surgical treatment of patients with Takayasu's arteritis."Circulation. 108. 1474-1480 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishikage S, Koyama Y, Miyata T, Shigematsu H.: "In vivo electroporation enhances plasmid-based gene transfer of basic fibroblast growth factor for the treatment of ischemic limb."Journal of Surgical Research. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyata T, Koyama H: "Regenerative Medicine of Vascular"Respiratory and Circulatory. 50(4). 377-383 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyata T, Sato O, Koyama H, Shigematsu H, Tada Y.: "Long-term survival after surgical treatment of patients with Takayasu's arteritis."Circulation. 108. 1474-1480 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishikage S, Koyama Y, Miyata T, Shigematsu H.: "In vivo electroporation enhances plasmid-based gene transfer of basic fibroblast growth factor for the treatment of ischemic limb."Journal of Surgical Research. (In press). (2004)

    • Related Report
      2003 Annual Research Report

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

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