Gene therapy for progressive renal diseases

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There is little doubt that molecular biological intervention therapy has come of age and tremendous excitements have emerged from its potential. A gene transfer technique, HVJ-liposome method is now applicable to the analysis of molecular aspects in pathophysiology of renal diseases, and further to a tool for gene therapy. We demonstrated that continuous delivery of chimeric soluble TGF-β receptor from the gene transferred skeletal muscle also inhibits the extracellular matrix expansion in experimental glomerulonephritis. Furthermore, we challenged whether in vivo gene transfer of antisense ODNs for TGF-β into interstitial fibroblasts can suppress the progression of interstitial fibrosis in unilateral ureteral obstruction model rats. Introduction of TGF-β1 antisense ODNs significantly reduced levels of TGF-β1 and types I collagen mRNA expression in obstructed kidneys, and consequently prevented the extent of interstitial fibrosis following ureteral obstruction. Taken together with clinical observation that up-regulation of TGF-β plays an important role in the formation of various kidney fibrosis, the manipulation of the overexpression of TGF-β may provide a novel way of therapeutic intervention to ameliorate the progression of the renal diseases.