Controlled dissemination of AAV vectors in the primate brain.

Adeno-associated viral (AAV) vectors are currently the preeminent gene therapy vehicles for neurological application. However, issues regarding the trafficking of AAV vectors within the primate brain, and consequently control over the targeting of transgene expression, remain a matter of investigation. Studies in nonhuman primates have shown that distribution of AAV vectors is largely mediated by the flow of cerebrospinal fluid within perivascular space, trafficking of vector along axonal projections, and AAV receptor binding. Together these processes can result in transduction of cells in areas distant from the parenchymal site of infusion. Additionally, we have addressed the unique surgical issues concerning delivery of AAV vectors by convection-enhanced delivery and are working toward tailored delivery by means of real-time MRI.