ABSTRACT

Adenoviruses (Ad) have been the subject of intense study since their isolation in the early 1950s (1). Over the past five decades, this study has greatly contributed to our understanding of many facets of Ad biology including fundamental aspects of the Ad life cycle, the dynamic interplay between Ad infection and the host immune response, and clinical disease associated with Ad infection. The discovery of the ability of Ad to deliver large amounts of DNA to the nucleus of an infected cell in a remarkably efficient manner prompted research aimed at developing Ad vectors for use as gene delivery vehicles. Ad vectors have long been recognized as particularly well suited for gene delivery in the therapy of genetic deficiency diseases such as Duchenne muscular dystrophy (DMD), given their broad tropism, large insert capacity, and their ability to infect quiescent cells. Ongoing studies delineating the molecular details of Ad infection and the host immune response continue to promote and guide innovative strategies designed to harness Ad for successful gene delivery to muscle. The purpose of this chapter is to summarize the major advances in Ad vector development, to present the progress in Ad-mediated gene transfer to dystrophin-deficient muscle, and to discuss the key hurdles that need to be overcome before Ad vectormediated gene therapy becomes a viable clinical therapeutic agent for the treatment of DMD.