Gene expression along the cerebral-spinal axis after regional gene delivery

We demonstrate here that intracerebroventricular or spinal cord (intratheca l) injection of either plasmid DNA alone or cationic liposome: DNA complexe s (CLDCs) produces significant levels of expression of both reporter genes and biologically relevant genes in nonparenchymal cells lining both the bra in and the spinal cord. Gene expression was identified both within the spin al cord and the brain after intracerebroventricular or intrathecal injectio n of either CLDCs or plasmid DNA alone. Intracerebroventricular or intrathe cal injection of CLDCs containing the beta-galactosidase (beta-Gal) gene pr oduced patchy, widely scattered areas of beta-Gal expression. The chloramph enicol acetyltransferase (CAT) reporter gene product reached peak levels be tween 24 hr and 1 week postinjection, and was still present at significant levels 3 weeks after a single intracerebroventricular or intrathecal inject ion. Intrathecal injection of the human granulocyte colony-stimulating fact or (G-CSF) gene produced high levels of hG-CSF activity in both the spinal cord and the brain. Intracerebroventricular injection of CLDCs containing t he murine nerve growth factor (NGF) gene increased mNGF levels in the hippo campus, a target region for cholinergic neurons in the medial septum, and i ncreased cholinergic neurotransmitter synthetic enzyme choline acetyltransf erase (ChAT) activity within the brain, a well-characterized effect of both purified and recombinant NGF protein. These findings indicate that intrace rebroventricular or intrathecal injection of CLDCs can produce significant levels of expression of biologically and therapeutically relevant genes wit hin the CNS.