Neuron-targeted gene transfer by adenovirus carrying neural-restrictive silencer element

Adenovirus transfers genes to a wide range of cell types, but its application to neurons has been hampered by its reduced efficiency of infection as compared with that for glia. To achieve neuron-targeted gene transfer, we have produced an adenovirus carrying the reporter lacZ gene driven by the SCG10 minimum promoter containing the neural-restrictive silencer element (NRSE), which element selectively represses the transcription of genes in non-neuronal cells. When rat hippocampal slice cultures were infected with NRSE-bearing adenovirus, beta-galactosidase-positive cells were mostly pyramidal and granular neurons, whereas infection with virus carrying a mutated NRSE resulted in beta-galactosidase expression in both neurons and glia. The results suggest that the adenovirus carrying NRSE to be a useful tool for neurontargeted gene transfer.