The submitted work details the development of a novel gene therapy vector capable of expressing multiple genes from a single transcript. This vector allows for high level therapeutic gene expression that is coupled to a dual reporter system that allows for real time in vivo tracking of gene expression as well as cellular detection without need for antibody staining. Additionally, a fusion protein was designed to specifically target the α- L -iduronidase protein to the central nervous system by way of the transferrin receptor. This treatment resulted in a decrease in glycosaminoglycan storage material in the brain of mucopolysaccharidosis type I mice. Lastly, we implemented the use of an episomally maintained plasmid-based vector that mediates high levels of protein production in vivo over a long period of time. Cumulatively this work has generated novel findings that will contribute to the field of gene therapy as a whole.
University of Minnesota Ph.D. dissertation. March 2009. Major: Microbiology, Immunology and Cancer Biology. Advisor: Bruce R. Blazar, M.D. 1 computer file (PDF); viii, 129 pages.
Osborn, Mark John.
Gene therapy strategies for targeting the treatment refractory sites in Hurler syndrome..
Retrieved from the University of Minnesota Digital Conservancy,
Content distributed via the University of Minnesota's Digital Conservancy may be subject to additional license and use restrictions applied by the depositor.