Determining tropism of recombinant adeno-associated viral vectors in vivo.

Undergraduates: Claire Storey, Blake Albright Aravind Asokan

Faculty Advisor: Dan McKay
Department: Biology

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For gene delivery to the central nervous system (CNS), adeno-associated vectors (AAV) must cross the blood-brain barrier (BBB). Producing effective levels of gene expression in the CNS requires high vector doses and consequently can be harmful to non-target organs such as the liver. To increase specificity of AAV vectors to the CNS as well as lower the dosage required, we used residues of two AAV serotypes known for specificity and their ability to cross the BBB. These serotypes, AAV1 and AAVrh.10, were combined to form a library of recombinant capsids that would be specific and able to cross the BBB. Select AAVrh.10 residues were identified to create AAV recombinants that were administered intravenously. These recombinants were detargeted from peripheral tissues while still maintaining their ability to transduce the CNS in vivo. The avoidance of non-target tissues by these recombinants offers support for a safer and more effective viral vector for gene delivery.