SBIR-STTR Award

Our objective is to test the concept of engineering the fiber protein of adenovirus to target adenovirus gene delivery vectors via cell type specific receptors. Our approach is to modify the adenovirus fiber protein by replacing the fiber head domain with ligands which bind to known cellular receptors which may be expressed in a cell specific manner. Modified fiber proteins will initially be expressed in vitro and in insect cells. The structure and receptor binding properties of chimeric fiber proteins will be assessed to determine whether the desired specificity has been achieved. Modified fibers will subsequently be introduced into the adenovirus genome using an adenovirus YAC, and the viability and cellular specificity of mutant adenoviruses will be assessed. The use of this approach to target adenovirus vectors carrying therapeutic genes such as the HSV-tk gene to tumor cells will be evaluated.National Cancer Institute (NCI)