Gene therapy with helper-dependent adenoviral vectors: lessons from studies in large animal models.

Abstract

Helper-dependent adenoviral vectors (HDAd) are deleted of all viral genes and they can efficiently transduce a wide variety of dividing and non-dividing cells to mediate high transgene expression levels. Unlike early generation adenoviral vectors, the absence of viral genes in HDAd results in long-term transgene expression without chronic toxicity and permits a large cloning capacity of 36kb. Moreover, HDAd genomes exist extra-chromosomally thus minimizing the risks of germline transmission and insertional mutagenesis. For these reasons, HDAd offers tremendous potential for in vivo gene therapy. This chapter reviews preclinical studies using HDAd in large animal models to assess safety and efficacy in a wide variety of gene therapy applications.