Helper-dependent adenoviral vectors for gene therapy of inherited diseases

Abstract

Helper-dependent adenoviral (HDAd) vectors that are devoid of all viral coding sequences are attractive vectors for gene therapy because they efficiently transduce a variety of cell types, have a large cloning capacity, have low risks of insertional carcinogenesis, and drive long-term transgene expression without chronic toxicity. The main limitation of HDAd vectors is the host innate inflammatory response elicited by capsid proteins that occurs shortly after intravascular administration and result in dose-dependent acute toxicity. Major efforts focused on elucidating adenoviral vector-host interactions have unraveled multiple factors involved in the acute toxicity. In this chapter, we provide a review of the most significant and advanced studies on the strategies to overcome the issue of acute toxicity and on the applications of these vectors for gene therapy of inherited diseases.