Vascular-targeted recombinant adeno-associated viral vectors for the treatment of rare diseases

ABSTRACT There is a lack of treatment options for many rare genetic disorders. Gene therapy represents a promising and innovative approach to fill this gap. One of such rare disorders is incontinentia pigmenti caused by X-linked deletions or mutations in the Nemo gene. The disease affects the skin, teeth, and eyes and, most importantly, it leads to a severe vascular pathology of the central nervous system. The genetic treatment of vascular disorders such as incontinentia pigmenti critically depends on safe and efficient gene delivery. Thus, focus has been set on the development of suitable vector systems. In a recent issue of EMBO Molecular Medicine, we describe the development of a recombinant adeno-associated viral (AAV) vector with a unique tropism for the brain vascular endothelium (termed AAV-BR1) and, as a proof of principle that may be transferred to other vascular disorders, report on its therapeutic application in a mouse model of incontinentia pigmenti. Here, we discuss the implications of our findings and further highlight the promising prospects as well as potential limitations of such vectors.