GENE-TRANSFER INTO THE ADULT KIDNEY FOR UNRAVELING DISEASE PROCESSES

Insights into the pathogenesis of human disease must be based on an un derstanding of the molecular mechanisms that regulate the structure an d function of individual organs. For this purpose, gene transfer techn ologies provide powerful and attractive tools. In principle, two diffe rent approaches are feasible to identify pathosphysiological roles of certain genes: 'gain-of-function', and 'loss-of-function'. The former examines consequences of overexpression of an exogenous gene, and the latter investigates the outcomes of inhibition of a particular molecul e via antigens, decoy, ribozyme and dominant-negative strategies. Gene transfer to specific renal structures allows evaluation of in vivo ef fects of certain molecules on the structure and function of each nephr on segment. It would also be useful for therapeutic intervention in re nal diseases through introduction of therapeutically relevant gens int o affected sites. This article summarizes current experience with rena l gene transfer and addresses its potential impacts on the understandi ng of renal function in vivo.