GENE-TRANSFER TO SYNOVIAL-CELLS BY INTRAARTICULAR ADMINISTRATION OF PLASMID DNA

We studied reporter gene expression in synovial tissue after intra-art icular administration of an expression plasmid into the knees of rabbi ts and rats, In both species, administration of a plasmid encoding bet a-galactosidase led to gene expression in the synovial cells lining th e joint, Expression correlated with the presence of plasmid DNA in syn ovial tissue extracts, Studies with a plasmid encoding chloramphenicol acetyltransferase demonstrated that gene expression persists for 2-5 days after administration. Southern blotting demonstrated that the adm inistered plasmid was taken up rapidly by synovial tissue and degraded , By 24 hr after administration, no intact plasmid could be detected b y Southern blotting, although small amounts of plasmid could be amplif ied by PCR up to 7 days, Administration of a plasmid encoding human gr owth hormone demonstrated that this product could be expressed from sy novial cells and secreted into the synovial fluid, The histological di stribution of gene expression in synovium resembles the known distribu tion of particulate materials injected into the joint and suggests tha t plasmid DNA is taken up by nonspecific endocytosis like other partic ulate materials during the remodeling of synovial fluid.