856. Transduction Patterns, Enzyme Distribution, and Vector and Enzyme Transport Resulting from Unilateral Injections of AAV 7, 8, 9, or Rh10 Expressing β-Glucuronidase into Select Brain Regions of the C3H Mouse

Abstract

AAV type 2 vector genome can be cross-packaged into multiple AAV serotypes. Our lab and others have shown that this can take advantage of the tissue tropisms of the different capsid proteins used. AAV serotypes 7, 8, 9, and Rh 10 are recently discovered serotypes from the rhesus monkey. We injected AAV vectors expressing the lysosomal enzyme |[beta]|-glucuronidase and containing capsid proteins from each of these serotypes into the brains of normal C3H mice. When injected into the brain, each serotype showed remarkably different transduction patterns and resulting enzyme spread at 2 months post-injection. AAV 9, when injected unilaterally into the hippocampus, showed vector transport to the hippocampus on the opposite side. Rh 10 showed the greatest amount of enzyme transport throughout the brain, and when injected into the thalamus, showed vector transport to other thalamic nuclei, not seen with other AAV serotypes. Injections of AAV 8 led to much less vector and enzyme transport than seen with other serotypes, suggesting that this serotype is not as specific for receptors found within the brain. The brains will be evaluated for vector and enzyme spread to specific cell types such as neurons and astrocytes using NSE and GFAP respectively. Mutant MPS VII mice will also be injected to determine if the widespread enzymatic correction results in widespread lysosomal storage correction. This information on the different AAV serotypes can be used for targeted transduction and for widespread correction in a variety of mouse lysosomal storage disease models with a neurological component.