Figure 5. Routes of vector entry in the context of the nephron.

(A) Blood enters the glomerulus of the nephron through the afferent arteriole, which has an approximate diameter of 20,000 nm. However, filtrate that penetrates further into the nephron is limited by the diameter of the slit diaphragms in the glomerular basement membrane, which are approximately 10 nm in diameter. The small diameter of the slit diaphragms excludes molecular therapy vectors from entering the kidney from the bloodstream, while the much broader diameter of the tubule epithelium (20,000 nm or greater) may allow entrance of vectors from the ureteral route. A high pressure delivery, I.E., a hydrodynamic injection, may change the principles of which vectors can pass through the glomerular barrier. (B) Vector access to the nephron after injection into the renal vein. Vectors may escape from the vasculature endothelium and access the basolateral surface of tubules (inset). (C) Vector access to the nephron after retrograde ureteral infusion. Vectors theoretically have exclusive access to the apical side of tubules, from the collecting duct to the proximal tubule (inset). (D) Vector access to the nephron after subcapsular injection. Vectors come into contact with tubules in a more undirected fashion, which theoretically is from “extra-tubular” space of kidney. Vectors may have access to basolateral or apical sides of tubules.