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Related Experiment Videos

Liver-directed gene transfer in non-human primates

D E Sullivan1, S Dash, H Du

  • 1Department of Pathology and Laboratory Medicine, Tulane University School of Medicine, New Orleans, LA 70112-2699, USA.

Human Gene Therapy
|July 1, 1997
PubMed
Summary

Adenovirus gene transfer to primate livers is efficient but causes immune responses and inflammation. Immunosuppression enables sustained reporter gene expression, suggesting potential for liver-directed gene therapy.

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Area of Science:

  • Gene Therapy
  • Hepatology
  • Immunology

Background:

  • Developing effective primate models is crucial for advancing liver-directed gene therapy.
  • Adenoviral vectors and lipofection are potential gene transfer methods for liver applications.
  • Understanding immune responses to gene transfer is key for therapeutic success.

Purpose of the Study:

  • To establish a non-human primate model for liver-directed gene therapy.
  • To evaluate different gene transfer vehicles and administration routes in rhesus monkeys.
  • To investigate the impact of immunosuppression on gene expression and immune response.

Main Methods:

  • Adenoviral vectors (Ad.CMVlacZ) or lipofection (pCMV beta) were used for gene transfer.
  • Gene constructs were administered via portal vein, common bile duct, or saphenous vein.

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  • Immunosuppression (cyclophosphamide/prednisone) was employed in a subset of animals.

    • Main Results:

    • Adenovirus via portal vein achieved >70% hepatocyte lacZ expression but caused acute hepatitis.
    • Immunosuppressed monkeys showed sustained lacZ expression (up to 35 days) without inflammation.
    • Lipofection was inefficient; adenovirus via common bile duct showed limited expression and inflammation.

    Conclusions:

    • Adenovirus-mediated gene transfer to primate livers is efficient but induces transient expression and immune responses.
    • Immunosuppression is critical for achieving sustained therapeutic gene expression in the liver.
    • This study highlights the potential of manipulating immune responses for effective liver gene therapy.