Engineered AAV vectors for improved central nervous system gene delivery.

Abstract

Adeno-associated viruses (AAV) are non-pathogenic members of the Parvoviridae family that are being harnessed as delivery vehicles for both basic research and increasingly successful clinical gene therapy. To address a number of delivery shortcomings with natural AAV variants, we have developed and implemented directed evolution-a high-throughput molecular engineering approach to generate novel biomolecules with enhanced function-to create novel AAV vectors that are designed to preferentially transduce specific cell types in the central nervous system (CNS), including astrocytes, neural stem cells, and cells within the retina. These novel AAV vectors-which have enhanced infectivity in vitro and enhanced infectivity and selectivity in vivo-can enable more efficient studies to further our understanding of neurogenesis, development, aging, and disease. Furthermore, such engineered vectors may aid gene or cell replacement therapies to treat neurodegenerative disease or injury.