Development of Novel Alternative Serotype Adenoviral Vectors for Gene Delivery in

DESCRIPTION (provided by applicant): Myriad studies have examined the potential of gene therapy in the inner ear. For the most part they have focused on adenoviral vectors and delivery into the cochlea. Most studies have emphasized looking at expression of marker genes driven by a CMV promoter and have used first generation adenoviral constructs based on the adenovirus serotype Ad5. The main advantages of the adenoviral delivery system are efficient gene delivery to most target tissues, the ease of synthesis and the ability to redirect adenoviral vectors to a variety of cell types and the advanced use of the vector system in the clinic. The main disadvantages of the current adenoviral delivery system is that gene delivery is not targeted for entry into specific cells in the inner ear and the Ad5 based vectors are strongly immunologically recognized in the human population. The proposed studies will test the hypothesis that adenoviral vectors based on non- Ad5 serotypes incorporating cell type specific promoters can be used to efficiently and specifically deliver proteins to the sensory cells and supporting cells of the inner ear. These new adenovirus vectors will overcome the limitations to the current Ad5 based system. During SBIR phase I we will first characterize and select novel adenoviral vector platforms that efficiently deliver genes to the inner ear and second test preferred vectors for selective expression in sensory cells and in supporting cells using specific promoter control elements. With these results in hand and the ever increasing genomic findings molecular therapeutics can be designed and tested that may treat inner ear disease. PUBLIC HEALTH RELEVANCE: This SBIR Phase 1 proposal tests the hypothesis that adenoviral vectors based on non- Ad5 serotypes incorporating cell type specific promoters can be used to efficiently and specifically deliver proteins to the sensory cells and supporting cells of the inner ear. These new adenovirus vectors will overcome the limitations to the current Ad5 based system. We will first characterize and select novel adenoviral vector platforms that efficiently deliver genes to the inner ear and second test preferred vectors for selective expression in sensory cells and in supporting cells using specific promoter control elements.