Strategic gene transfer into the kidney: Current status and prospects

Abstract

Progress in gene transfer technology has established the scientific basis for molecular approaches to human diseases. In the kidney, the first trial of gene transfer was reported in 1991, and several strategies have been developed during the past years. Successful gene transfer into specific renal structures allows for evaluation of in vivo effects of certain molecules on the structure and function of the kidney. It would also be useful for therapeutic intervention in renal diseases by introducing “beneficial” genes into the affected sites. By introducing viral vectors or liposomes via particular access routes, it is feasible to selectively manipulate function of certain renal structures. Through the renal circulation, exogenous genes can be targeted to the vasculature, glomeruli and proximal tubules. Using a retrograde approach via the urinary tract, access to collecting ducts is possible. Implantation of genetically modified cells under the capsule of the kidney allows for diffusion of transgene products into the interstitium. Transplantation of embryonic metanephric kidneys also provides a biological window for renal gene transfer. Furthermore, germline gene manipulations are becoming realistic strategies for creation of “transgenic kidneys” and “gene knockout kidneys.’ This article summarizes the current experince with gene transfer into the kidney and addresses its potential impact on nephrology.