Large or Food Animal and Equine Medicine Commons^™

Therapeutic Neonatal Hepatic Gene Therapy In Mucopolysaccharidosis Vii Dogs, Katherine Parker Ponder, John R. Melniczek, Lingfei Xu, Margaret A. Weil, Thomas M. O'Malley, Patricia A. O'Donnell, Van W. Knox, Gustavo D. Aguirre, Hamutal Mazrier, N Matthew Ellinwood, Margaret M. Sleeper, Albert M. Maguire, Susan W. Volk, Robert L. Mango, Jean Zweigle, John H. Wolfe, Mark E. Haskins

Gustavo D. Aguirre, VMD, PhD

Dogs with mucopolysaccharidosis VII (MPS VII) were injected intravenously at 2–3 days of age with a retroviral vector (RV) expressing canine β-glucuronidase (cGUSB). Five animals received RV alone, and two dogs received hepatocyte growth factor (HGF) before RV in an attempt to increase transduction efficiency. Transduced hepatocytes expanded clonally during normal liver growth and secreted enzyme with mannose 6-phosphate. Serum GUSB activity was stable for up to 14 months at normal levels for the RV-treated dogs, and for 17 months at 67-fold normal for the HGF/RV-treated dog. GUSB activity in other organs was 1.5–60% of normal at 6 months for …