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Basic Research of Gene Therapy using Adenoviral Vector for Muscular Dystrophy

Research Project

Project/Area Number 05454264
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionNatinal Center of Neurology and Psychiatry

Principal Investigator

ARAHATA Kiichi (1994)  Department of Neuromuscular Research, National Institute of Neuroscience, Director, 神経研究所・疾病研究第一部, 部長 (30053325)

杉田 秀夫 (1993)  国立精神・神経センター, 総長 (80009951)

Co-Investigator(Kenkyū-buntansha) TSUKAHARA Toshifumi  Dept.of Neuromuscular Research, National Institute of Neuroscience, Investigator, 神経センター・神経研究所・疾病研究第一部, 研究員 (60207339)
TAKEDA Shinichi  Dept.of Neuromuscular Research, National Institute of Neuroscience, Section Chie, 神経センター・神経研究所・疾病研究第一部, 室長 (90171644)
荒畑 喜一  神経研究所, 疾病研究第一部, 部長 (30053325)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1994: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1993: ¥5,100,000 (Direct Cost: ¥5,100,000)
KeywordsGene transfer / Adenoviral vector / Cultured muscle cells / Regenerated muscle tissue / Muscular dystrophy / Gene therapy / 再生筋 / beta‐galactosidase(lacZ)遺伝子 / ジストロフィン遺伝子 / ミオシンH鎖IIBプロモーター / 正荷電リポソーム
Research Abstract

The effective gene transfer using adenoviral vector has been done in cultured muscle cells and in regenerated rat muscle tissue.
1) Gene transfer into cultured muscle cells
We used two recombinant adeno viruses, Adex CA-1acZ,where 1ac Z was driven by ubiquitous strong promoter, and Adex MHC IIB-1acZ,where 1acZ was driven by muscle-specific promoter. When Adex CA 1acZ was transferred into mouse myogenic cell line, C2 cells under the condition of m.o.j 10,1ac Z was effectively transcribed and beta-galactosidase was apparent in all the cultured cells. When this recombinant adeno virus was infected into differentiated C2 cells, beta-galactosidase activities has been found even at large myotubes. This finding clearly showed that recombinant adeno virus can be transfected into post-mitotic cells. In the experiments with Adex MHC IIB-1acZ,beta-galactosidase activity was prominent only when recombinant adenovirus was infected into fully differentiated cells. This activation pattern reflects the character of MHC-IIB promoter, which was active in adult muscle tissue.
2) Gene transfer into the regenerated rat muscle tissue
Adex CA-1ac Z has been injected into rat soleus muscle. Effective gene transfer has been detected, when muscle regeneration was induced by Bupivacaine treatment prior to recombinant adenoviral infection.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Sekijima,Y.et al.: "A case of cytoplasmic myopathy with hypertrophic…" Jpn J Int Med. (in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshida,K.et al.: "A mutant in the ceruloplasmin gene is associated with…" Nature Genet. (in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeda,S.et al.: "Myogenic regulatory factors can activate TATA-containing promoter…" J.Biol.Chem.(in press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 宮越友子、他: "筋の発生・分化の分子機構" 小児科臨床. 47. 2435-2439 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 石井亜紀子,他: "デュシャンヌ型筋ジストロフィー/Duchenne muscular dystrophy" 実験医学. 12. 121-125 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 武田伸一: "DMD遺伝子/ジストロフィンの異常と拡張型心筋症" 内科. 75. 441-446 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 石井亜紀子(分担執筆): "クリニカル・ファーマシーのための内科学" 医薬ジャーナル社, 563 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 武田伸一(分担執筆): "臨床遺伝医学VI" 診断と治療社(印刷中), (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sekijima Y.et al.: "A case of cytoplasmic body myopathy with hypertrophic cardiomyopathy" Jpn J Int Med. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yoshida, Y.et al.: "A mutation in the ceruloplasmin gene is associated with systermic hemosiderosis in humans" Nature Genet. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeda, S.et al.: "Myogenic regulatory factors can activate TATA-containing promoter elements via an E-box independent mechanism." J.Biol.Chem.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ishii, A.et al.: "Duchenne muscular dystrophy" Experimental Medicine. 12. 121-125 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Miyagoe, Y.: "Molecular mechanism of myogenesis." Shounika-Rinsyou. 47. 2439-2445 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeda, S.et al.: "The basis of molecular genetic diagnosis-Perspective" Clinical Neuroscience. 12. 381-383 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeda, S.: "Abnormality of DMD gene/dystrophin and dilated cardiomyopathy" Medicine. 75. 441-446 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ishii, A.et al.: Progressive muscular dystrophy "Internal medicine for clinical pharmacy". Iyaku-Journal-Sya, 563 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takeda, S.et al.: Gene Therapy for Duchenne muscular dystrophy. "Clinical Genetic Medicine VI". Shindann-to-Chiryou-Sya (in press).,

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sekijima,Y.et al.: "A case of cytoplasmic myopathy with hypertrophic---" Jpn J Int Med. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshida,K.et al.: "A mutant in the ceruloplasmin gene is associated with---" Nature Genet. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takeda,S.et al.: "Myogenic regulatory factors can activate TATA-containing promoter---" J.Biol.Chem.(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 宮越友子、他: "筋の発生・分化の分子機構" 小児科臨床. 47. 2439-2435 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 石井亜紀子,他: "デュシャンヌ型筋ジストロフィー/Duchenne muscular dystrophy" 実験医学. 12. 121-125 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 武田伸一: "DMD遺伝子/ジストロフィンの異常と拡張型心筋症" 内科. 75. 441-446 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 石井亜紀子(分担執筆): "クリニカル・ファーマシーのための内科学" 医薬ジャーナル社, 563 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 武田伸一(分担執筆): "臨床遺伝医学 VI" 診断と治療社(印刷中), (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshida,K.et al.: "Molecular analysis of the Duchenne musclar dystrophy gene..." Muscle&Nerve. 16. 1161-1166 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Arahata,K.et al.: "Laminin in animal models for muscular dystrophy,Defect of..." Proc.Japan Acad.69,B. 259-264 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Takeda,S.et al.: "Mutations in the DMD gene and cardiomyopathy in Becker..." Neuromuscular Disorders. (in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] 武田伸一,他: "筋の発生に関与する遺伝子" 最新医学. 48. 493-499 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 武田伸一,他: "筋ジストロフィー(DMD,BMD)" Brain Nursing. 9. 731-736 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 武田伸一(分担執筆): "Annual Review神経 1994" 中外医学社, 370 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 中尾洋子、他(分担執筆): "遺伝子診断" 羊土社, 190 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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