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.

R01DK067324

2004-04-01

2015-06-30