Gene therapy strategies for targeting the treatment refractory sites in Hurler syndrome.

摘要

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 alpha-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.