Transduction characteristics of alternative adeno-associated virus serotypes in the cat brain by intracisternal delivery

Multiple studies have examined the transduction characteris-tics of different AAV serotypes in the mouse brain, where they can exhibit significantly different patterns of transduc-tion. The pattern of transduction also varies with the route of administration. Much less information exists for the transduc-tion characteristics in large-brained animals. Large animal models have brains that are closer in size and organization to the human brain, such as being gyrencephalic compared to the lissencephalic rodent brains, pathway organization, and certain electrophysiologic properties. Large animal models are used as translational intermediates to develop gene thera-pies to treat human diseases. Various AAV serotypes and routes of delivery have been used to study the correction of pa-thology in the brain in lysosomal storage diseases. In this study, we evaluated the ability of selected AAV serotypes to transduce cells in the cat brain when delivered into the cerebrospinal fluid via the cisterna magna. We previously showed that AAV1 trans-duced significantly greater numbers of cells than AAV9 in the cat brain by this route. In the present study, we evaluated sero-types closely related to AAVs 1 and 9 (AAVs 6, AS, hu32) that may mediate more extensive transduction, as well as AAVs 4 and 5, which primarily transduce choroid plexus epithelial (CPE) and ependymal lining cells in the rodent brain. The related serotypes tended to have similar patterns of transduc-tion but were divergent in some specific brain structures.