DISTRIBUTION OF THE CELLULAR UPTAKE OF PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES IN THE RAT-KIDNEY IN-VIVO

Previous animal studies have demonstrated that following systemic admi nistration phosphorothioate oligodeoxynucleotides (S-ODNs) are primari ly excreted by the kidneys and that renal tissue levels of S-ODNs exce ed that of other organs, Thus, the kidney may be an ideal target organ for application of antisense S-ODNs in vivo, We examined which cells within the rat kidney have uptake of radiolabeled S-ODNs following int ravenous infusion. A 20-base S-35-ODN was infused into 6 adult male Wi star rats. Three animals each were sacrificed 30 min and 4 h after inf usion. The kidneys were then removed, fixed, and tissue autoradiograph y was performed. Similar results were obtained in both groups, The hig hest level of radioactivity was seen within the proximal tubules. Lowe r levels of activity were seen within the glomerulus, the parietal epi thelial cells of Bowman's space, and distal tubular cells, Very weak a ctivity was also detected within the cells of the loop of Henle and th e medullary collecting ducts. These results demonstrated that within t he kidney S-ODNs were taken up primarily by proximal tubular cells, wi th much lower uptake by cells in other segments of the nephron.