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Heart Failure pp 199-208 | Cite as

In Vivo Gene Supplementation for the Therapy of Cardiomyopathy

  • Tomie Kawada
  • Yoko Nakatsuru
  • Aiji Sakamoto
  • Toshiyuki Koizumi
  • Wee Soo Shin
  • Mikio Nakazawa
  • Jun-Ichi Suzuki
  • Toshiyuki Nakajima
  • Yoshio Uehara
  • Tsuyoshi Takato
  • Hiroshi Sato
  • Takatoshi Ishikawa
  • Teruhiko Toyo-Oka
Conference paper

Abstract

We have identified the gene defect and breakpoint of δ-sarcoglycan (SG) in cardiomyopathic (CM) BIO 14.6 hamsters, which are a representative model of human cardiomyopathy. The aim of the present study is to explore a gene therapy using gene transfection to in vivo myocardial cells that we have previously established. Liposomes containing a reporter gene (β-galactosidase, β-Gal) with or without the δ-SG gene were coated with UV-inactivated hemagglutinating virus of Japan and injected into the left ventricular free wall in anesthetized open-chest CM hamsters. We prepared site-directed antibody to the extracellular domain of the δ-SG protein, the amino acid sequence of which was deduced from the cloned cDNA. Affinity-purified antibody demonstrated a single band after Western blotting in the normal Syrian hamster heart but no band in the CM heart. On day 7 after the transfection, hearts were removed and fixed. The adjacent cryosections were immunostained with antibody to β-Gal or δ-SG using the ABC procedure. The δ-SG gene product was clearly expressed in both sarcolemma and cytoplasm of cardiomyocytes of CM hamsters, whereas the β-Gal protein was exclusively coexpressed in the cytosol, showing the efficient cotransfection of both β-Gal and δ-SG genes and the slow protein traffic to the sarcolemma after biosynthesis of δ-SG in cytoplasm. We have succeeded in an efficient expression of the δ-SG gene in living CM hamster hearts with deleted δ-SG gene, suggesting that the newly developed in vivo gene transfection might be promising for the rescue of targeted CM cells.

Key words

Cardiomyopathy Gene transfection BIO14.6 δ-Sarcoglycan HVJ-liposomes 

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Copyright information

© Springer-Verlag Tokyo 2000

Authors and Affiliations

  • Tomie Kawada
    • 1
  • Yoko Nakatsuru
    • 2
  • Aiji Sakamoto
    • 3
  • Toshiyuki Koizumi
    • 4
  • Wee Soo Shin
    • 6
  • Mikio Nakazawa
    • 5
  • Jun-Ichi Suzuki
    • 6
  • Toshiyuki Nakajima
    • 6
  • Yoshio Uehara
    • 6
  • Tsuyoshi Takato
    • 4
  • Hiroshi Sato
    • 1
  • Takatoshi Ishikawa
    • 2
  • Teruhiko Toyo-Oka
    • 6
  1. 1.Pharmacy DivisionNiigata University Medical HospitalNiigataJapan
  2. 2.Department of PathologyUniversity of TokyoTokyoJapan
  3. 3.Biotechnology DivisionNational Cardiovascular Research CenterOsakaJapan
  4. 4.Maxillofacial SurgeryUniversity of TokyoTokyoJapan
  5. 5.Department of PharmacologyNiigata UniversityNiigataJapan
  6. 6.The 2nd Department of Internal MedicineTokyo University Hospital, Health Service CenterTokyoJapan

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