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Sci Rep. 2017 Mar 20;7:44904. doi: 10.1038/srep44904.

Kidney-specific transposon-mediated gene transfer in vivo.

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Department of Veterans Affairs, Nashville, TN 37212 USA.
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 USA.
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232 USA.
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232 USA.
Department of Veterans Affairs, Houston, TX 77030 USA.


Methods enabling kidney-specific gene transfer in adult mice are needed to develop new therapies for kidney disease. We attempted kidney-specific gene transfer following hydrodynamic tail vein injection using the kidney-specific podocin and gamma-glutamyl transferase promoters, but found expression primarily in the liver. In order to achieve kidney-specific transgene expression, we tested direct hydrodynamic injection of a DNA solution into the renal pelvis and found that luciferase expression was strong in the kidney and absent from extra-renal tissues. We observed heterogeneous, low-level transfection of the collecting duct, proximal tubule, distal tubule, interstitial cells, and rarely glomerular cells following injection. To assess renal injury, we performed the renal pelvis injections on uninephrectomised mice and found that their blood urea nitrogen was elevated at two days post-transfer but resolved within two weeks. Although luciferase expression quickly decreased following renal pelvis injection, the use of the piggyBac transposon system improved long-term expression. Immunosuppression with cyclophosphamide stabilised luciferase expression, suggesting immune clearance of the transfected cells occurs in immunocompetent animals. Injection of a transposon expressing erythropoietin raised the haematocrit, indicating that the developed injection technique can elicit a biologic effect in vivo. Hydrodynamic renal pelvis injection enables transposon mediated-kidney specific gene transfer in adult mice.

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