We have developed a balloon occlusion catheter method of delivering helper-dependent adenoviral vectors preferentially into the liver of nonhuman primates. This method results in high efficiency hepatocyte transduction and high level, long-term transgene expression with minimal toxicity. In this application, we propose to address the few outstanding issues before potential clinical application of this technology.
Specific Aim 1 is to eliminate the hypotension that is associated with our balloon occlusion method of vector delivery thereby enhancing safety.
Specific Aim 2 is to determine the % hepatoctye transduction achievable with various vector doses delivered by our balloon occlusion method to permit better assessment of risk:benefit.
Specific Aim 3 is to determine the safety and efficacy of delivering a helper-dependent adenoviral vector expressing canine coagulation factor IX by the balloon method into FIX-deficient dogs as a model for hemophilia B gene therapy.
Gene therapy has the potential to cure genetic and acquired diseases. This application proposes to refine and test a novel method of performing gene therapy. We will also evaluate our unique gene therapy technique in a dog model of a human bleeding disorder.
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|Palmer, Donna J; Ng, Philip (2011) Characterization of helper-dependent adenoviral vectors. Cold Spring Harb Protoc 2011:867-70|
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|Prill, Jan-Michael; Espenlaub, Sigrid; Samen, Ulrike et al. (2011) Modifications of adenovirus hexon allow for either hepatocyte detargeting or targeting with potential evasion from Kupffer cells. Mol Ther 19:83-92|
|Khare, Reeti; May, Shannon M; Vetrini, Francesco et al. (2011) Generation of a Kupffer cell-evading adenovirus for systemic and liver-directed gene transfer. Mol Ther 19:1254-62|
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