Adenoviral-mediated Gene Therapy in Lung Transplantation

grantor: University of TorontoGene therapy provides the potential to modify donor organs to better withstand the process of transplantation, although successful application in this setting has yet to be realized. In vivo adenoviral-mediated gene transfer induces a host immune response producing inflammation and limiting the amount and duration of transgene expression. By administering triple-immunosuppression, as is routine in lung transplantation, transgene expression can be increased and prolonged following both initial and repeat transfection, making transplantation a viable setting for the application of gene therapy. Intratracheal adenoviral-mediated gene transfection of the donor lungs produces positive transgene expression in the lungs at the time of reperfusion and following lung transplantation. Donor transfection produces higher levels of transgene expression than ex vivo transfection of the previously harvested organ, without affecting other transplantable organs. Lung transplantation, therefore, with its obligate immunosuppression and ability to achieve local transfection, provides an unique and advantageous setting for the application of gene therapy strategies.M.Sc