Lentiviral gene transduction of kidney.
Gene transfer into kidney holds great potential as a novel therapeutic approach. We have studied the transduction of kidney in vivo after delivery of lentiviral vectors by various routes of administration. A lentiviral vector expressing the bacterial lacZ gene from the cytomegalovirus early promoter was used. The lentiviral vector was delivered into the kidneys of BALB/c mice by retrograde infusion into the ureter, by injection into the renal vein or artery, or by direct injection into the renal parenchyma. Expression of the reporter gene was achieved independently of the route of administration, although it appeared more efficient after parenchymal or ureteral administration. After parenchymal or ureteral infusion, expression of the transgene was localized to the outer medulla and corticomedullary junction. In the case of parenchymal injection, expression of the reporter gene extended to the cortex. Detection of the transgene in the renal proximal tubules was confirmed by in situ polymerase chain reaction after parenchymal or ureteral infusion. On delivery of the lentiviral vector through the renal artery or vein, expression of the reporter gene was markedly lower than was observed with parenchymal or ureteral infusion and was limited to the inner medullary collecting ducts. No apparent histological abnormality was observed after virus administration and transgene expression was stable for at least 3 months. These results provide the first evidence that lentiviral vectors can stably transduce renal cells in vivo and may be effective vehicles for gene delivery to the kidney.
Gusella, GL; Fedorova, E; Hanss, B; Marras, D; Klotman, ME; Klotman, PE
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