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We have developed an ex vivo method for delivering genes to the synovial lining of joints and expressing them intra-articularly. The present studies were designed to determine whether transfer of a human interleukin-1 receptor antagonist protein (IRAP) gene by this method was able to antagonize the intra-articular actions of interleukin-1. Intra-articular injections of human recombinant interleukin-1 beta (hrIL-1 beta) into the knees of control rabbits provoked a marked leukocytic infiltrate into the joint space, severe synovial thickening and hypercellularity, and loss of proteoglycans from articular cartilage. Genetically modified knees contained several nanograms of human IRAP and inhibited each of these effects of IL-1 beta. These data demonstrate for the first time that delivery of an appropriate gene to joints can prevent intra-articular pathology. Such findings permit cautious optimism about the eventual development of a gene treatment for arthritis and other disorders of the joint.

Type

Journal article

Journal

Gene Ther

Publication Date

01/1994

Volume

1

Pages

64 - 69

Keywords

Animals, Arthritis, DNA, Complementary, Gene Transfer Techniques, Genetic Therapy, Genetic Vectors, Humans, Injections, Intra-Articular, Interleukin 1 Receptor Antagonist Protein, Interleukin-1, Joint Diseases, Rabbits, Recombinant Proteins, Retroviridae, Sialoglycoproteins, Synovial Membrane