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Development of new therapy that combines gene transfer into serious failing heart with RNAi

Research Project

Project/Area Number 17591484
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Thoracic surgery
Research InstitutionNara Medical University

Principal Investigator

TSUJI Tsuyoshi  Nara Medical University, School of Medicine, assistant professor., 医学部, 講師 (50295804)

Co-Investigator(Kenkyū-buntansha) TAKAKI Miyako  Nara Medical University, School of Medicine, chief professor, 医学部, 教授 (00033358)
YOSHIKAWA Yoshiro  Nara Medical University, School of Medicine, assistant professor, 医学部, 講師 (40343420)
NAKAJIMA Chikako  Nara Medical University, School of Medicine, assistant professor, 医学部, 助手 (50336848)
TAMURA Yamato  Nara Medical University, School of Medicine, assistant professor, 医学部, 助手 (20382301)
桑田 俊之  奈良県立医科大学, 医学部, 助手 (00398439)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsSERCA2a / Phospholamban / RNAi / Gene transfer / failing heart
Research Abstract

We have reported that the cardiac function and the survival rate are improved to the rat severe heart failing model by over expressed of the sarcoplasmic reticulum Ca^<2+>ATPase (SERCA2a) gene. Moreover, we have enhanced the SERCA2a function in controlling Phospholamban (PLB) that is the suppresser protein of SERCA2a by the anti sense method. We have paid attention to ratio of PLB and SERCA2a (PLB/SERCA2a ratio) and treated serious failing hearts. It is difficult to try gene transfer for a large animal and the human whole heart using adenovirus. The method has not been established yet. While the gene expression is discovered to be suppressed by RNAi (RNA interference : RNA interference) in C. elegans in recent topics, there is a similar mechanism in the mammal. It has been reported the very effective method of gene silencing by using small RNA in mammal. Then, the aim of this research is to develop a new safety and effective treatment for serious heart failure, combining RNAi and the gene transfer. It came to be able to gene transfer in this year under the ultrasonic guide instead of under the X-ray. Moreover, we had heard an information of invalidity of siRNA in vivo at another laboratory though it was effective in vitro. It has been difficult for us to get effective siRNA for PLB in vivo. While we have reported repeatedly about the effectiveness of SERCA2a for the serious heart failure. Now we start non-viral safety procedure, near future it will be a promising clinical application.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (8 results)

All 2007 2006 Other

All Journal Article (8 results)

  • [Journal Article] Transcoronary gene transfer of SERCA2a increases coronary blood flow and decreases cardiomyocyte size in a type II diabetic rat model.2007

    • Author(s)
      Susumu Sakata, Tsuyoshi Tsuji, Miyako Takaki et al.
    • Journal Title

      American Journal of Physiology : Heart & Circ Physiol 292

      Pages: 1204-1207

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Transcoronary gene transfer of SERCA2a increases coronary blood flow and decreases cardiomyocyte size in a type II diabetic rat model.2007

    • Author(s)
      Susumu Sakata, Tsuyoshi tsuji, Miyako Takaki et al.
    • Journal Title

      American Journal of Physiology : Heart & Circ Physiol 292

      Pages: 1204-1207

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Mechanical and Metabolic Rescue in Type II Diabetes Model of Cardiomyopathy by Targeted Gene Transfer2006

    • Author(s)
      Susumu Sakata, Miyako Takaki et al.
    • Journal Title

      Molecular Therapy Vol. 13,No. 5

      Pages: 987-996

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mechanical and Metabolic Rescue in Type II Diabetes Model of Cardiomyopathy by Targeted Gene Transfer2006

    • Author(s)
      Susumu Sakata, Miyako Takaki et al.
    • Journal Title

      Molecular Therapy Vol. 13, No. 5

      Pages: 987-996

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Mechanical and Metabolic Rescue in Type II Diabetes Model of Cardiomyopathy by Targeted Gene Transfer2006

    • Author(s)
      Susumu Sakata, Miyako Takaki et al.
    • Journal Title

      Molecular Therapy Vol.13, No.5

      Pages: 987-996

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins

    • Author(s)
      Susumu Sakata, Tsuyoshi Tsuji, et al.
    • Journal Title

      Journal of Molecular and Cellular Cardiology (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins

    • Author(s)
      Susumu Sakata, Tsuyoshi Tsuji, et al.
    • Journal Title

      Journal of Molecular and Cellular Cardiology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins

    • Author(s)
      Susumu Sakata, Tsuyoshi tsuji et al.
    • Journal Title

      Journal of Molecular and Cellular Cardiology (In press)

    • Related Report
      2006 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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