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Cellular biological study on the treatment of Duchenne muscular dystrophy with nucleic acids

Research Project

Project/Area Number 16390301
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKobe University

Principal Investigator

MATSUO Masafumi  Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (10157266)

Co-Investigator(Kenkyū-buntansha) TAKESHIMA Yasuhiro  Kobe University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (40281141)
YAGI Mariko  Kobe University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (60362787)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2005: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 2004: ¥8,900,000 (Direct Cost: ¥8,900,000)
Keywordsdystrophin / exon skipping / antisense / Duchenne / DMD
Research Abstract

Duchenne muscular dystrophy (DMD) is a fatal muscle-wasting disease, and its victims usually succumb in their twenties. Many studies, including investigations into gene-replacement therapy, have been conducted in a search for a treatment for DMD, and the most promising treatment to date is rescue of mutant dystrophin mRNA by induction of exon skipping. On the basis of results from the molecular analysis of dystrophin Kobe, we have proposed a treatment for DMD in which antisense oligonucleotides induce exon skipping to edit out-of frame dystrophin mRNA into in-frame, thereby converting severe DMD to a milder form. Here we conducted studies on development of RNA/ENA chimeric oligonucleotide for the treatment of DMD. At first we searched for the best RNA/ENA chimera that has ability to induce skipping of target exon. After repeating trials to induce exon skipping in cultured myocytes, we succeeded to identify the most powerful RNA/ENA chimera for exon skipping. The identified RNA/ENA chimera was transfected to a DMD patient's cultured myocytes and shown to induce dystrophin expression. This treatment strategy was examined for application to mouse treatment. We obtained a knockout mouse that has a deletion of exon 52 of the dystrophin gene. By identifying a proper RNA/ENA chimera, we are going to induce exon 51 skipping in the model mouse.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (27 results)

All 2005 2004

All Journal Article (25 results) Book (2 results)

  • [Journal Article] A novel cryptic exon identified in the 3' region of intron 2 of the human dystrophin gene.2005

    • Author(s)
      Van Khanh, T., et al.
    • Journal Title

      J Hum Genet 50

      Pages: 425-433

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Intraperitoneal administration of phosphorothioate antisense oligodeoxynucleotide against splicing enhancer sequence induced exon skipping in dystrophin mRNA expressed in mdx skeletal muscle.2005

    • Author(s)
      Takeshima, Y., et al.
    • Journal Title

      Brain Dev 27

      Pages: 488-493

    • NAID

      10017132332

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Rescue of dystrophin mRNA of Duchenne muscular dystrophy by inducing exon skipping.2005

    • Author(s)
      Matsuo, M. et al.
    • Journal Title

      Acta Myologica XXIV

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel approach to identify Duchenne muscular dystrophy patients for aminoglycoside antibiotics therapy.2005

    • Author(s)
      Kimura, S., et al.
    • Journal Title

      Brain Dev 27・6

      Pages: 400-5

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A G-to-A transition at the fifth position of intron 32 of the dystrophin gene inactivates a splice donor site both in vivo and in vitro.2005

    • Author(s)
      Thi Tran, HT., et al.
    • Journal Title

      Mol Gen Metab 85

      Pages: 213-219

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel cryptic exon identified in the 3' region of intron 2 of the human dystrophin gene.2005

    • Author(s)
      Tran, V.K., et al.
    • Journal Title

      J Hum Genet 50

      Pages: 425-433

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Rescue of dystrophin mRNA of Duchenne muscular dystrophy by inducing exon skipping.2005

    • Author(s)
      Matsuo, M., et al.
    • Journal Title

      Acta Myologica XXIV

      Pages: 110-114

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel approach to identify Duchenne muscular dystrophy patients for aminoglycoside antibiotics therapy.2005

    • Author(s)
      Kimura, S., et al.
    • Journal Title

      Brain Dev 27

      Pages: 400-405

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A G-to-A transition at the fifth position of intron 32 of the dystrophin gene inactivates a splice donor site both in vivo and in vitro.2005

    • Author(s)
      Thi Tran, HT, et al.
    • Journal Title

      Mol Gen Metab 85

      Pages: 213-219

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel cryptic exon identified in the 3' region of intron 2 of the human dystrophin gene.2005

    • Author(s)
      Tran, V.K.
    • Journal Title

      J Hum Genet 50

      Pages: 425-433

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intraperitoneal administration of phosphorothioate antisense oligodeoxynucleotide against splicing enhancer sequence induced exon skipping in dystrophin mRNA expressed in mdx skeletal muscle.2005

    • Author(s)
      Takeshima, Y.
    • Journal Title

      Brain Dev 27

      Pages: 488-493

    • NAID

      10017132332

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Rescue of dystrophin mRNA of Duchenne muscular dystrophy by inducing exon skipping.2005

    • Author(s)
      Matsuo, M.
    • Journal Title

      Acta Myologica XXIV

      Pages: 110-114

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A novel approach to identify Duchenne muscular dystrophy patients for aminoglycoside antibiotics therapy.2005

    • Author(s)
      Kimura, S.
    • Journal Title

      Brain Dev 27

      Pages: 400-405

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A G-to-A transition at the fifth position of intron 32 of the dystrophin gene inactivates a splice donor site both in vivo and in vitro.2005

    • Author(s)
      Hoai, T., T, T
    • Journal Title

      Mol Gen Metab 85

      Pages: 213-219

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Chimeric RNA and 2'-O, 4'-C-ethylene-bridged nucleic acids have stronger activity than phosphorothioate oligodeoxynucleotides in induction of exon 19 skipping in dystrophin mRNA.2004

    • Author(s)
      Yagi, M., et al.
    • Journal Title

      Oligonucleotides 14

      Pages: 33-40

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Design of 2'-0-Me RNA/ENATM chimera oligonucleotides to induce exon skipping in dystrophin pre-mRNA.2004

    • Author(s)
      Takagi, M., et al.
    • Journal Title

      Nucleic Acids Symposium Series 48

      Pages: 297-298

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Chimeric RNA/ethylene-bridged nucleic acids promote dystrophin expression in myocytes of duchenne muscular dystrophy by inducing skipping of the nonsense mutation-encoding exon.2004

    • Author(s)
      Surono, A., et al.
    • Journal Title

      Hum Gene Ther 15

      Pages: 749-757

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] C-terminal Truncated Dystrophin Identified in Skeletal Muscle of an Asymptomatic Boy with a Novel Nonsense Mutation of the Dystrophin Gene.2004

    • Author(s)
      Suminaga, R., et al.
    • Journal Title

      Pediatr Res 56

      Pages: 739-743

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cloning of cDNA encoding a regeneration-associated muscle protease whose expression is attenuated in cell lines derived from Duchenne muscular dystrophy patients.2004

    • Author(s)
      Nakayama, Y., et al.
    • Journal Title

      Am J Pathol 164

      Pages: 1773-1782

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] C-terminal Truncated Dystrophin Identified in Skeletal Muscle of an Asymptomatic Boy with a Novel Nonsense Mutation of the Dystrophin Gene2004

    • Author(s)
      Suminaga R
    • Journal Title

      Pediatric Research 56

      Pages: 739-743

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Design of 2'-O-Me RNA/ENA^<TM> chimera oligonucleotides to induce exon skipping in dystrophin pre-mRNA2004

    • Author(s)
      Takagi M
    • Journal Title

      Nucleic Acids Symposium Series 48

      Pages: 297-298

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cloning of cDNA Encoding a Regeneration-associated Muscle Protease Whose Expression is Attenuated in Cell Lines Derived from Duchenne Muscular Dystrophy Patients2004

    • Author(s)
      Nakayama Y
    • Journal Title

      American Journal of Pathology 164

      Pages: 1773-1782

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A novel deletion creating a new terminal exon of the dihydrolipoyl transacylase gene is a founder mutation of Filipino maple syrup urine disease2004

    • Author(s)
      Catherine Lynn T.Silao
    • Journal Title

      Mol Genet Metab 81

      Pages: 100-104

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Chimeric RNA and 2'-O, 4'-C-ethylene-bridged nucleic acids have stronger activity than phosphorothioate oligodeoxynucleotides in induction of exon-19 skipping in dystrophin mRNA2004

    • Author(s)
      Yagi M
    • Journal Title

      Oligonucleotides 14

      Pages: 33-40

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Chimeric RNA/ethylene bridged nucleic acids promote dystrophin expression in myocytes of Duchenne muscular dystrophy by inducing skipping of the nonsense-mutation-encoding exon2004

    • Author(s)
      Surono A
    • Journal Title

      Hum Gene Ther 15

      Pages: 749-757

    • Related Report
      2004 Annual Research Report
  • [Book] からだの科学増刊 『高度先進医療』(進行性筋ジストロフィーのDNA診断)2005

    • Author(s)
      片山義規
    • Publisher
      日本評論社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] RNAiとアンチセンス法-新しいRNAの科学と応用(医療の立場からのアンチセンス法)2005

    • Author(s)
      松尾雅文
    • Publisher
      講談社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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