220. AAV Mediated Gene Transfer of Smad7 in Different Models of Cystic Kidney Diseases

• Published in: Molecular therapy Vol. 13; no. S1; p. S85
• Main Authors: Keppler, Andrea, Leuchs, Barbara, Stump, Carolin, Dooley, Steven, Kleinschmidt, Juergen, Gretz, Norbert
• Format: Journal Article
• Language: English
• Published: Milwaukee Elsevier Limited 01.05.2006
• Subjects: Cloning; Gene expression; Gene therapy; Genomes; Infections; Kidney diseases; Leukemia; Mutation; Pediatrics; Vectors (Biology); La Jolla California; California; United States > US; Germany
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2006.08.245

Cystic diseases of the kidney (CDK) with consecutive interstitial fibrosis represent the most frequent hereditary causes of end-stage renal failure in children and adults. Up to now no causal treatment for any of them is available in humans. It is shown that the TGF-β pathway is playing a major role in the development of interstitial fibrosis and an overexpression of Smad7, the negative inhibitor of TGF-β, is able to prevent fibrosis. Therefore we want to analyse the effect of a long term expression of Smad7 on renal function and interstitial fibrosis in our CDK animal models.To achieve this goal we produced an adeno associated virus (AAV-2) expressing Smad7. 1E11 genome containing particles were injected into the rat kidney via a femoral catheter and 48h after infection the expression of Smad7 in the kidney and a spectrum of other organs was tested. We could show 48h after infection an increase of Smad7 expression in the infected kidneys up to 7 fold compared to control animals. Now we started a long term experiment with 3 month of AAV-2 mediated Smad7 expression in the CDK animals. In this study we will analyse the development of renal function over time. Finally histology will be performed with special emphasis on interstitial fibrosis and cyst number and size.