The following application is to support an inter-institutional Program of Excellence in Gene Therapy (PEGT). The participating institutions include: Stanford University, The Children's Hospital of Philadelphia, University of Pennsylvania, University of California-San Francisco and investigators with a well-documented history of collaboration. In this application, there are 4 pre-clinical gene therapy proposals and 3 clinical trials within two clinical projects. There are two """"""""local"""""""" core proposals (for the investigators of this PEGT), a Research Grade AAV and Clinical Core. In addition, we propose a National Data Management and National Morphology Core. The proposals within the PEGT have two common themes; gene based therapies for hemophilia (projects 1, 2, 3, 5, 6) and recombinant adeno-associated viruses as a vector for pre-clinical and clinical gene transfer (projects 1-6). A brief summary of each project follows: (#1) Dr. Katherine High will test the hypothesis that the bleeding diathesis in hemophilia patients with inhibitory antibodies can be treated with a gene therapy approach. This grant builds on a decade of clinical experience with recombinant VIIa and on the investigator's expertise with coagulation proteins and their expression using AAV vectors. (#2) Dr. Haig Kazazian and colleagues will work in collaboration with Drs. High and Kay to develop optimal liver-based rAAV vectors for factor VIII deficiency, and then test those vectors in appropriate pre-clinical pre- clinical animal models. (#3) Dr. Mark Kay plans to develop a non- surgical asanguinous liver perfusion technology in large animals for tissue specific delivery of vectors a prelude to clinical application, and to address important biological questions related to AAV transduction of liver. His group will use this approach for preclinical evaluation of a new integrating, non-viral vector. (#4) Dr. Y.W. Kan proposes pre-clinical trial using rAAV in a unique manner for hypoxia induced vascular angiogenesis that could be used in treating coronary artery disease. (#5) Dr. Bert Glader proposes two liver-based AAV trials for hemophilias A and B. (#6) Dr. Catherine Manno has developed a new AAV muscle- based clinical trial for factor IX deficiency based on proposed preclinical studies to select an improved expression cassette, vector serotype, and site of vector injection. This highly interactive group of scientific and clinical investigations is likely to enhance progress in clinical gene therapy.
Showing the most recent 10 out of 36 publications
