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Transgenic plants expressing human glutamic acid decarboxylase (GAD65), a major autoantigen in insulin-dependent diabetes mellitus

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Abstract

Parenteral and oral administration of autoantigens can induce immune tolerance in autoimmune diseases. Prophylactic therapy based on oral administration of human autoantigens is not, however, feasible when sufficient quantities of candidate autoantigens are not available. Transgenic plants that express high levels of recombinant proteins would allow large quantities of autoantigens to be produced at relatively low costs. In addition, transgenic food would provide a simple and direct method of delivering autoantigens. The production and the characterization of transgenic tobacco and carrot plants expressing human GAD65, a major autoantigen in human insulin-dependent diabetes mellitus (IDDM), is reported. Immunogold labeling and electron microscopy of transgenic tobacco tissue shows the selective targeting of human GAD65 to chloroplast tylacoids and mitochondria. In planta expressed GAD65 has a correct immunoreactivity with IDDM-associated autoantibodies and retains enzymatic activity, a finding that suggests a correct protein folding. In transgenic tobacco and carrot the expression levels of human GAD65 varies between 0.01% and 0.04% of total soluble proteins. Transgenic edible plant organs are now available to study the feasibility of inducing immune tolerance in IDDM animals by oral administration of GAD65.

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Authors and Affiliations

  1. Istituto di Miglioramento Genetico Vegetale, Italy

    Andrea Porceddu, Nicoletta Ferradini, Franco Lorenzetti & Mario Pezzotti

  2. Dipartimento di Medicina Interna e Scienze Endocrine e Metaboliche, Università degli Studi di Perugia, Perugia, Italy

    Alberto Falorni, Anna Cosentino, Filippo Calcinaro & Paolo Brunetti

  3. Dipartimento di Scienze Ambientali, Università degli, Studi di Siena, Siena, Italy

    Claudia Faleri & Mauro Cresti

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  1. Andrea Porceddu
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  2. Alberto Falorni
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  4. Anna Cosentino
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Porceddu, A., Falorni, A., Ferradini, N. et al. Transgenic plants expressing human glutamic acid decarboxylase (GAD65), a major autoantigen in insulin-dependent diabetes mellitus. Molecular Breeding 5, 553–560 (1999). https://doi.org/10.1023/A:1009605729268

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