Preferential transduction of neurons by canine adenovirus vectors and their efficient retrograde transport in vivo

In the central nervous system (CNS), there are innate obstacles to the modi fication of neurons: their relative low abundance versus glia and oligodend rocytes, the inaccessibility of certain target populations, and the volume one can inject safely. Our aim in this study was to characterize the in viv o efficacy of a novel viral vector derived from a canine adenovirus (CAV-2) . Here we show that CAV-2 preferentially transduced i) rat olfactory sensor y neurons; ii) rodent CNS neurons in vitro and in vivo; and, more clinicall y relevant, iii) neurons in organotypic slices of human cortical brain. CAV -2 also showed a high disposition for retrograde axonal transport in vivo. We examined the molecular basis of neuronal targeting by CAV-2 and suggest that due to CAR (coxsackie adenovirus receptor) expression on neuronal cell s-and not oligodendrocytes, glia, myofibers, and nasal epithelial cells-CAV -2 vectors transduced neurons preferentially in these diverse tissues.