A NEURAL CELL-TYPE-SPECIFIC EXPRESSION SYSTEM USING RECOMBINANT ADENOVIRUS VECTORS

We demonstrated neural cell-type-specific gene expression using an ade novirus vector, which is useful, for delivering foreign genes into qui escent neural cells. We produced eight recombinant replication-defecti ve adenoviruses carrying the lacZ reporter gene driven by various prom oters, including those of the L7/PCP2 gene (highly restricted expressi on in cerebellar Purkinje cells), and the myelin basic protein (in oli godendrocytes) gene. We demonstrated in vitro and in vivo promoter-dri ven, neural cell-type-specific gene expression by recombinant adenovir uses. The genes were transferred into these recombinant adenoviruses a nd expressed with high levels of efficiency in vitro and in vivo. In p rimary culture, the recombinant adenoviruses AdexL7-NL-LacZ and AdexMB P-NL-LacZ appeared to be expressed in a Purkinje cell and oligodendroc yte-specific manner. Introduction of 10(8) pfu of these viruses into t he adult rat cerebellum by stereotactic injection yielded neural cell- type-specific expression without apparent toxicity to the animals. Thu s, adenovirus vectors are useful for cell-type-specific therapeutic us es and in studies requiring neural cell-type-specific gene expression.