Gene transfer by naked DNA into adult mouse brain

Nonviral gene transfer into the central nervous system could provide a basis for therapeutic uses and fundamental research. We show that naked DNA injected intracerebrally into the mouse brain can provide expression of a reporter protein. Expression is dose dependent, being maximal for 150 mu g DNA injected. We observed less than 5 days expression of the luciferase transgene, which is not improved with plasmid preparations virtually free of lipopolysaccharide. Thus, the adult brain behaves as striated muscle for naked DNA uptake and transcription, albeit at a much lower efficiency. In neither adult brain nor muscle did complexation of DNA with cationic lipid improve transgene expression. Double immunolabeling using cell-specific markers shows that both neurons and glia are transfected by naked DNA gene transfer methodology.