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Immunity and tolerance induction in gene therapy

Part 1. Genetics

1.7. Gene Therapy

Short Specialist Review

  1. Jean Davoust,
  2. Nicolas Bertho,
  3. Carole Masurier,
  4. David Gross

Published Online: 15 NOV 2005

DOI: 10.1002/047001153X.g107305

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

How to Cite

Davoust, J., Bertho, N., Masurier, C. and Gross, D. 2005. Immunity and tolerance induction in gene therapy. Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics. 1:1.7:99.

Author Information

  1. Généthon, Evry, France

Publication History

  1. Published Online: 15 NOV 2005

Abstract

Gene and cell therapies are promising for long-term reconstitution of diseased tissues, and for restoration of therapeutic levels of circulating proteins, correcting inherited genetic disorders. Among the fundamental biological questions raised, the immune response to gene therapy is of great importance as it can hinder the success of gene correction. The onset of an immune response depends on the mutational genotype in each patient; the strength of antitransgene responses may also vary depending on gene delivery methods, based on plasmids, viral vectors or cell vectors, and on the route of injection. As a result, in most gene therapy protocols, the immune system will detect the packaging viral proteins and the transgene itself, causing humoral and cellular responses, which may lead to complete eradication of the corrected cells whenever the transgene protein behaves as a truly foreign antigen, that is, its sequence is partially or completely absent from the host. In this review, we will consider three main goals of immunology research in the field of gene therapy, namely, (1) deciphering dendritic cell/viral vector interactions, (2) inducing antigen-specific tolerance for long-term reconstitution of diseased tissues, and (3) monitoring immune responses to gene transfer in humanized animal models carrying HLA transgenes.

Keywords:

  • gene transfer;
  • muscular dystrophy;
  • immune responses;
  • viral vectors;
  • dendritic cells;
  • regulatory T cells;
  • tolerance induction;
  • HLA molecules;
  • animal models;
  • immunomonitoring