My primary research interests focus on the development and clinical translation of gene therapy vectors with the goal to achieve effective new treatments for serious human diseases. With basic training in biochemistry, immunology and virology, I have subsequently been engaged for approx 20 years in the development of virus-based new biologic products. My lab has supported gene therapy at the preclinical and clinical trial stages for treatment of various genetic diseases, including hemophilia B and RPE65 Leber Congenital Amaurosis (a form of blindness), infectious diseases including those caused by HIV and HCV, and for other serious diseases including Parkinson's Disease and cancer. We have established methodologies to generate, purify and characterize recombinant adeno-associated virus (AAV)- and recombinant Lentivirus -based gene transfer vector at a scale sufficient to support large animal studies and clinical trials. My lab has published widely, including reports of innovations relating to gene therapy vector design and development in specialized gene therapy journals, and as part of multi-disciplinary teams, the results of clinical trials described in broader interest journals including Nature Medicine, The New England Journal of Medicine, and The Lancet. A particular research interest is to investigate and understand barriers presented by host (human) immune defenses against viral vectors, with the objective to develop 'humanized' viral vectors retaining the highly efficient target cell transduction efficiency inherent with viral vectors, but with minimized activation of immune responses.
I direct a Clinical Vector Core Laboratory that designs, prepares and certifies recombinant adeno associated viruses (AAV) for use as investigational new drugs in clinical studies. The Core Laboratory follows current Good Manufacturing Practices (cGMP) required for early phase clinical studies. Several ongoing and planned clinical studies, including recombinant AAV-mediated delivery of the gene encoding retina pigment epithelium associated 65kDa protein (RPE65) for Leber's Congenital Amaurosis (Maguire et al. Safety and efficacy of gene transfer for Leber's Congenital Amaurosis. The New England Journal of Medicine 358:2240-2248, 2008), and recombinant AAV-mediated delivery of the gene encoding coagulation factor IX (f.IX) for hemophilia B (Manno et al. Successful transduction of liver in hemophila B by AAV-Factor IX and limitations imposed by the host immune response. Nature Medicine 12:342-347, 2006), are supported by the Clinical Vector Core Laboratory.
back to top
Last updated: 06/03/2013
The Trustees of the University of Pennsylvania