Every little bit helps: A single-residue switch in a vascular AAV enables blood-brain barrier penetration

The clinical potential of adeno-associated virus (AAV) vectors as gene delivery tools for neurological diseases is constrained by the low capacity of natural AAV capsids to cross the blood-brain barrier (BBB). As a result, delivery of AAV vectors to the central nervous system (CNS) requires high vector doses or invasive local delivery, both associated with significant risks of vector-induced toxicity. To overcome this limitation, multiple groups have attempted to generate engineered AAV capsids with improved BBB penetration and CNS transduction.