ADENOVIRAL-MEDIATED GENE-TRANSFER TO RABBIT SYNOVIUM IN-VIVO

Currently, treatment for rheumatoid arthritis and other inflammatory a rthropathies is often ineffective in ameliorating the progression of t he disease, particularly the invasive destruction of cartilage and bon e by rheumatoid synovium. Multiple aspects of this inflammatory proces s are mediated by the synovial lining cells (synoviocytes). Genetic mo dification of these cells in vivo represents a potential method for th e treatment of these conditions. In this report, we describe a novel t echnique for the genetic transduction of synovial lining cells in vivo using recombinant adenoviral vectors and intraarticular injection tec hniques. Purified high titer suspensions of a recombinant adenoviral v ector containing the gene for Escherichia coli beta-galactosidase ( Ad CMVlacZ) were directly injected into the hind knees of New Zealand whi te rabbits. Synovial tissues were then examined for transgenic lacZ ex pression using a combination of in situ staining for beta-galactosidas e activity, immunohistochemical staining, and transmission electron mi croscopy. High efficiency gene transfer and lacZ expression was observ ed in both type A and type B synoviocytes throughout the articular and periarticular synovium of the rabbit knee, with continued expression of transgenic lacZ detected for greater-than-or-equal-to 8 wk after in fection.