Expression of Escherichia coli beta-galactosidase and rat HPRT in the CNS of Macaca mulatta following adenoviral mediated gene transfer.
Adenoviral-mediated gene transfer to the caudate nucleus of Macaca mulatta was accomplished using stereotactic injection of two distinct recombinant Ad5 vectors containing the gene for Escherichia coli beta-galactosidase and the cDNA for rat hypoxanthine-guanine phosphoribosylphosphotransferase (HPRT), respectively. Multiple analyses (including immunohistochemistry, histochemistry, transmission electron microscopy, RNA in situ hybridization, nucleotide pool analysis, and enzyme assay) confirmed efficient expression of beta-galactosidase and rat HPRT. Transgene expression was evident in both neurons and glia. Clinically, no evidence of meningitis or cerebritis was observed and no focal neurological deficits were detected in the animal. These preliminary studies indicate that recombinant adenovirus is capable of mediating high level transgene expression to the brains of higher order mammals.
Davidson
B L
BL
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0680.
Doran
S E
SE
Shewach
D S
DS
Latta
J M
JM
Hartman
J W
JW
Roessler
B J
BJ
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002421:Caudate Nucleus / Q000502:physiology*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007763:Lac Operon / Q000502:physiology; D007926:Lesch-Nyhan Syndrome / Q000201:enzymology / Q000235:genetics; D008253:Macaca mulatta; D051381:Rats; D001616:beta-Galactosidase / Q000235:genetics*
D007041:Hypoxanthine Phosphoribosyltransferase; D001616:beta-Galactosidase