Genetic Modification of Renal Epithelial Cells in PKD

Project Description Narrative:

End-stage renal failure is a serious problem that is continuing to increase as the population ages throughout the United States, and polycystic kidney disease (PKD) remains one of the reasons attributed to this growing epidemic trend. Therapies to treat polycystic kidney disease have remained elusive due to a lack of knowledge regarding the underling etiology of this proliferative disease.

This project will study the use of alternatively pseudotyped lentiviral vectors to genetically modify the renal epithelial cells in the kidneys affected by PKD. The objectives of this research will be to determine the optimal route of administration to achieve efficient transduction into the cystic epithelial cells as well as maintain persistent lentiviral-mediated transgene expression and to understand the biology of epigenetic silencing mechanisms and whether different promoter-transgene cassettes will be able to perform more effectively in the context of lentiviral vectors from one another.

The project will offer a novel method to mechanistically manipulate individual target gene products, even those with extremely close sequence homology, to better understand the proliferative role of eicosanoids in PKD.