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 nak ed DNA injected intracerebrally into the adult 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 expre ssion of the luciferase transgene, which is not improved with plasmid preparations virtually free of lipopolysaccharide. Thus, the adult bra in behaves as striated muscle for naked DNA uptake and transcription, albeit at a much lower efficiency. In neither adult brain nor muscle d id complexation of DNA with cationic lipid improve transgene expressio n. Double immunolabeling using cell- specific markers show that both n eurons and glia are transfected by naked DNA gene transfer methodology .