Efficient gene transfer and long-term expression in neurons using a recombinant adenovirus with a neuron-specific promoter

Adenoviruses are highly efficient vectors for gene transfer into brain cell s. Restricting transgene expression to specific cell types and maintaining long-term expression are major goals for gene therapy in the central nervou s system. We targeted gene expression to neurons by constructing an adenovi ral vector that expressed the E. coli LacZ reporter gene under the control of the rate neuron-specific enolase promoter (Ad-NSE). Expression from Ad-N SE was compared with that from and adenoviral vector encoding the same repo rter gene under the control of the Rous sarcoma virus LTR promoter (Ad-RSV) . Both recombinant adenoviruses were injected stereotactically into rat hip pocampus, cerebellum and striatum. Anatomical and immunohistochemical analy ses of the Ad-NSE-stained cells showed that neurons were preferentially tra nsduced. More neurons were stained in the hippocampus following infection w ith Ad-NSE than with Ad-RSV. Cytotoxicity from Ad-NSE was lower than from A d-RSV. beta-Galactosidase gene expression after Ad-NSE infection remained s table for 3 1/2 months, and was detectable for 6 months. Thus, the NSE-aden oviral vector can be used to transfer potentially therapeutic genes into ne uronal cells. The use of a cell-specific promoter also resulted in high in vivo efficiency and longterm transgene expression.