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.

KEYWORDS:

• adeno-associated virus
• blood-brain barrier
• endothelial cells
• gene therapy
• incontinentia pigmenti
• neurovascular disease

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Disclosure of potential conflicts of interest

The University Medical Center Hamburg-Eppendorf (UKE) has filed a patent application for the capsid-modified AAV vector BR1 on behalf of the authors. The authors have no additional competing financial interests.

Acknowledgments

We thank all authors of the original article “A brain microvasculature endothelial cell‐specific viral vector with the potential to treat neurovascular and neurological diseases” in EMBO Mol Med.

Funding

This work was supported by the German Research Foundation (DFG, grants TR448/11-1 to MT and SCHW416/9-1 to MS) and the Margarethe Clemens Foundation (endowed professorship to MT).