GENETIC MANIPULATION OF THE KIDNEY

Successful gene transfer into specific renal structures allows for eva luation of in vivo effects of certain molecules on the structure and f unction of the kidney. It would also be useful for therapeutic interve ntion in renal diseases by introducing ''beneficial'' genes into the a ffected sites. Towards achieving these goals, several gene transfer ap proaches have been developed using retrovirus, adenovirus and liposome . By introducing these gene transfer vectors via particular access rou tes, it is feasible to selectively manipulate the function of certain renal structures. Through the renal circulation, exogenous genes can b e targeted to the vasculature and glomerulus, and possibly to the prox imal rubles. Using a retrograde approach via the urinary tract, access to the collecting ducts can be gained. Implantation of genetically mo dified cells under the capsule of the kidney allows for diffusion of t ransgene products into the interstitium. Transplantation of embryonic metanephric tissues also provides a biological window for genetic mani pulation. Furthermore, utilisation of fertilised eggs or embryonic ste m cells would enable the creation of ''transgenic kidneys'' or ''gene knockout kidneys''. This article summarises the current experience wit h gene transfer to the kidney and addresses the potential strategies i n vivo.