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Gene therapy of autoimmune diseases with vectors encoding regulatory cytokines or inflammatory cytokine inhibitors
Author(s) -
Prud'homme Gérald J.
Publication year - 2000
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/1521-2254(200007/08)2:4<222::aid-jgm117>3.0.co;2-p
Subject(s) - immunology , medicine , cytokine , arthritis , autoimmunity , tumor necrosis factor alpha , genetic enhancement , dna vaccination , immune system , biology , gene , biochemistry , immunization
Gene therapy offers advantages for the immunotherapeutic delivery of cytokines or their inhibitors. After gene transfer, these mediators are produced at relatively constant, non‐toxic levels and sometimes in a tissue‐specific manner, obviating limitations of protein administration. Therapy with viral or nonviral vectors is effective in several animal models of autoimmunity including Type 1 diabetes mellitus (DM), experimental allergic encephalomyelitis (EAE), systemic lupus erythematosus (SLE), colitis, thyroiditis and various forms of arthritis. Genes encoding transforming growth factor β, interleukin‐4 (IL‐4) and IL‐10 are most frequently protective. Autoimmune/inflammatory diseases are associated with excessive production of inflammatory cytokines such as IL‐1, IL‐12, tumor necrosis factor α (TNFα) and interferon γ (IFNγ). Vectors encoding inhibitors of these cytokines, such as IL‐1 receptor antagonist, soluble IL‐1 receptors, IL‐12p40, soluble TNFα receptors or IFNγ‐receptor/IgG‐Fc fusion proteins are protective in models of either arthritis, Type 1 DM, SLE or EAE. We use intramuscular injection of naked plasmid DNA for cytokine or anticytokine therapy. Muscle tissue is accessible, expression is usually more persistent than elsewhere, transfection efficiency can be increased by low‐voltage in vivo electroporation, vector administration is simple and the method is inexpensive. Plasmids do not induce neutralizing immunity allowing repeated administration, and are suitable for the treatment of chronic immunological diseases. Copyright © 2000 John Wiley & Sons, Ltd.