Over the last few decades, the utility of viral vectors has expanded from their initial use as clinical therapeutics for debilitating genetic diseases to include their use as vaccination platforms. When deciding on the optimal viral vector for use, considerations must be made that include target tissue, dose, immunogenicity, and overall safety. Adenovirus vectors have been a compelling vector in gene therapy due to their ability to package large gene-of-interest transgenes. Conversely, while adeno-associated viruses (AAV) have one of the smallest packaging capacities, the wide tissue tropism between different serotypes has made them a select candidate for tissue specific applications even with systemic delivery.