Direct in vivo gene transfer to ependymal cells in the central nervous system using recombinant adenovirus vectors

To evaluate the potential for adenovirus–mediated central nervous system (CMS) gene transfer, the replication deficient recombinant adenovirus vectors Ad.RSVβgal (coding for β–galactosidase) and Ad–α1AT (coding for human α1–antitrypsin) were administered to the lateral ventricle of rats. Ad.RSVβgal transferred β–galactosidase to ependymal cells lining the ventricles whereas Ad–α1AT mediated α1 –antitrypsin secretion into the cerebral spinal fluid for 1 week. These observations, together with β–galactosidase activity in the globus pallidus and substantia nigra following stereotactic administration of Ad.RSVβgal to the globus pallidus, suggest that adenovirus vectors will be useful for CNS gene therapy.