IN-VIVO ADENOVIRUS-MEDIATED GENE-TRANSFER INTO NORMAL AND CYSTIC RAT KIDNEYS

Gene transfer into the mammalian kidney has proved difficult because o f the structural complexity of the organ and its low mitotic index. Th is article describes the use of intra-arterially injected adenovirus t o study gene transfer into the rat kidney in vivo. By pre-chilling the kidney, and incubating the virus with the kidney in the cold for exte nded periods of time, we were able to successfully transfer a beta-gal actosidase (beta-gal) reporter gene into the vasculature without ische mic injury to the kidney. Transfer occurred largely in the cortex when cold was used alone, whereas with the use of cold and vasodilators, t ransfer was accomplished into the outer medulla in both the inner and outer stripes. In the Han:SPRD rat model of autosomal dominant polycys tic kidney disease (ADPKD), gene transfer occurred into the vasculatur e, some epithelial cysts and interstitial cells. This is the first des cription of substantial in vivo gene transfer into both normal and cys tic kidneys. The methodology could find application in the creation of new models of renal disease, for in vivo therapeutic intervention of ro genetic modification of an allograft at the time of harvest.