Global non-viral gene transfer to the primate brain following intravenous administration.
Expression plasmids encoding either luciferase or beta-galactosidase were encapsulated in the interior of an "artificial virus" comprised of an 85 nm pegylated immunoliposome, which was targeted to the rhesus monkey brain in vivo with a monoclonal antibody (MAb) to the human insulin receptor (HIR). The HIRMAb enables the liposome carrying the exogenous gene to undergo transcytosis across the blood-brain barrier and endocytosis across the neuronal plasma membrane following intravenous injection. The level of luciferase gene expression in the brain was 50-fold higher in the rhesus monkey as compared to the rat. Widespread neuronal expression of the beta-galactosidase gene in primate brain was demonstrated by both histochemistry and confocal microscopy. This approach makes feasible reversible adult transgenics in 24 hours.
Zhang
Yun
Y
Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90024, USA.
Schlachetzki
Felix
F
Pardridge
William M
WM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D004705:Endocytosis; D018014:Gene Transfer Techniques; D008156:Luciferases / Q000235:genetics; D008253:Macaca mulatta; D018613:Microscopy, Confocal
D000911:Antibodies, Monoclonal; D008156:Luciferases