Adeno-associated Virus-Mediated Gene Delivery Across the Blood-Brain Barrier

Recombinant adeno-associated viruses (AAVs) have emerged as a popular tool for gene therapy in the central nervous system (CNS). Given the dense vasculature in the CNS, systemic administration is an appealing approach for achieving a broad distribution of AAV vectors across the CNS. However, the blood-brain barrier (BBB) is a major obstacle that blocks the entry of AAV vectors into the brain and spinal cord. Thus, there is a great need to develop novel AAV vector technology with enhanced BBB penetration. In this chapter, we briefly summarize AAV biology, possible mechanisms for AAV vectors to overcome the BBB and further engineering strategies, and current clinical trials using systemic AAV gene therapy for CNS diseases.