Genetic manipulation of the kidney

Abstract

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. Towards achieving these goals, several gene transfer approaches have been developed using retrovirus, adenovirus and liposome. By introducing these gene transfer vectors via particular access routes, it is feasible to selectively manipulate the function of certain renal structures. Through the renal circulation, exogenous genes can be targeted to the vasculature and glomerulus, and possibly to the proximal tubules. Using a retrograde approach via the urinary tract, access to the collecting ducts can be gained. Implantation of genetically modified cells under the capsule of the kidney allows for diffusion of transgene products into the interstitium. Transplantation of embryonic metanephric tissues also provides a biological window for genetic manipulation. Furthermore, utilisation of fertilised eggs or embryonic stem cells would enable the creation of "transgenic kidneys" or "gene knockout kidneys". This article summarises the current experience with gene transfer to the kidney and addresses the potential strategies in vivo.

Double transduction of a Cre/LoxP lentiviral vector: a simple method to generate kidney cell-specific knockdown mice

“…To deliver genes or shRNA in a specific organ, the route of administration is an important aspect. Specifically for the kidney, although several invasive delivery techniques (20,29,37), via the renal artery, renal vein, and ureter, or by direct １７ parenchymal injection, have been developed and used in small rodents, hydrodynamic tail vein (28) delivery has recently been regarded as a simple and effective method for gene transfer into these animals. Kobayashi et al (21)(22)(23) showed that hydrodynamic intravenous injection of pU6-stem21, a model siRNA-expressing vector, resulted in significant suppression of the target transgene expression in the liver, kidney, and lung.…”

Renal transplantation in children

“…Furthermore, transplantation of embryonic metanephric tissue and the use of fertilized eggs or embryonic stem cells would enable the creation of a transgenic kidney or ‘gene‐knockout’ kidney. However, further research is needed to identify the regulatory elements required for kidney‐directed germline gene manipulation [28].…”