Gene transfer with high-capacity „gutless”︁ adenoviral vectors

Abstract

The elucidation of the pathogenesis of inherited and acquired disorders will stimulate the design of novel therapies. Somatic gene therapy may become a very interesting alternative or addition to many drug-based treatment modalities. Efficient and non-toxic gene delivery is critical for a successful implementation of somatic gene therapy. High-capacity adeno�viral (HC-Ad) vectors have some features that make them very promising reagents to achieve this goal. With low toxicity, they can efficiently transduce different primary cell types in vitro and in vivo. In addition, they can deliver DNA fragments with sizes of up to 35 kb which allows the simultaneous expression of several genes or the tight control of gene expression by including regulatory control elements. Preclinical studies in mice suggest that long-term gene expression can be achieved from this vector type. Thus, safety, duration of expression, and versatility is considerably improved compared to previous-generation adenoviral vectors.