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1994 Fiscal Year Final Research Report Summary

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

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)
Project Period (FY) 1993 – 1994
KeywordsGene transfer / Adenoviral vector / Cultured muscle cells / Regenerated muscle tissue / Muscular dystrophy / Gene therapy / 再生筋
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.

  • Research Products

    (17 results)

All Other

All Publications (17 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1996-04-15  

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