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- W2563316904 abstract "Using adeno-associated virus (AAV)-based gene therapy to treat renal diseases is an underdeveloped area. Renal anatomy and physiology make gene delivery to this organ especially difficult. Multiple AAV serotypes and routes of entry in rodents have been tried, with the majority of combinations targeting the renal tubules. To improve upon the current methods of AAV renal transduction for future use in the clinical setting, we employed direct intrarenal pelvis injections of AAV2, 6, 8 and 9 with the luciferase (Luc) or GFP transgene under the control of the cytomegalovirus (CMV) or putative kidney-specific promoters from myo-inositol oxygenase(MIOX), acyl-CoA synthetase medium-chain family member 2 (Acsm2), uromodulin (UMOD), kidney androgen-regulated protein (Kap) and solute carrier family 34 (sodium phosphate), member 1 (Slc34a1) mouse genes in C57Bl/6J mice. Renal luciferase transgene expression was strongest with AAV6, 8 and 9-CMV-Luc. AAV6 and 8-CMV-Luc resulted in stronger expression in the injected kidney, whereas AAV9-CMV-Luc showed equal, bilateral renal expression. AAV9 with the UMOD promoter gave the strongest and most highly renal-specific luciferase expression among all serotype and kidney promoter combinations. Using the GFP transgene we further established AAV transduction of multiple cell types in the kidney. AAV8-CMV-GFP transduced both glomerular and tubular renal cells, while AAV9-CMV-GFP most strikingly transduced periglomerular tubule cells. Both AAV8 and AAV9-UMOD-GFP solely transduced renal tubule cells. We are currently testing AAV variants isolated from clinical urine samples to determine their ability to transduce renal cells in vivo. Our results demonstrate efficient renal transduction by direct intrarenal pelvis injection of AAV vectors. Coupling specific renal cell tropisms of AAV serotypes and renal cell-type-specific promoters, along with the intrarenal pelvis injection strategy would pave the way for a renal-targeted AV gene therapy." @default.
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- W2563316904 date "2016-05-01" @default.
- W2563316904 modified "2023-09-25" @default.
- W2563316904 title "307. Hitting the Kidney from All Angles: Using Direct Intrarenal Pelvis Injection Combined with Serotype and Promoter Targeting to Achieve Renal AAV Gene Delivery" @default.
- W2563316904 doi "https://doi.org/10.1016/s1525-0016(16)33116-1" @default.
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