EXPRESSION OF ESCHERICHIA-COLI BETA-GALACTOSIDASE AND RAT HPRT IN THECNS OF MACACA-MULATTA FOLLOWING ADENOVIRAL MEDIATED GENE-TRANSFER

Adenoviral-mediated gene transfer to the caudate nucleus of Macaca mul atta was accomplished using stereotactic injection of two distinct rec ombinant Ad5 vectors containing the gene for Escherichia coil beta-gal actosidase and the cDNA for rat hypoxanthine-guanine phosphoribosylpho sphotransferase (HPRT), respectively. Multiple analyses (including imm unohistochemistry, histochemistry, transmission electron microscopy, R NA in situ hybridization, nucleotide pool analysis, and enzyme assay) confirmed efficient expression of beta-galactosidase and rat HPRT. Tra nsgene expression was evident in both neurons and glia. Clinically, no evidence of meningitis or cerebritis was observed and no focal neurol ogical deficits were detected in the animal. These preliminary studies indicate that recombinant adenovirus is capable of mediating high lev el transgene expression to the brains of higher order mammals. (C) 199 4 Academic Press, Inc.