Expression of a functional foreign gene in adult mammalian brain following in Vivo transfer via a herpes simplex virus type 1 defective viral vector.

Overview

We report here the first use of a herpes simplex virus defective viral vector for the transfer and expression of a foreign gene in the adult rat brain in vivo. Defective vectors offer unique advantages over other systems. Our vector genome consists of multiple copies of a plasmid-based amplicon, with a human cytomegalovirus promoter and lacZ gene as a reporter. Helper functions were provided by an HSV1 mutant incapable of replication at physiological temperatures. The resulting defective viral vector was stereotaxically microinjected into rat hippocampus and hypothalamus, and cells expressing functional beta-galactosidase were detected in both areas. Expression was confined to regions at or near the site of injection. Positive cells were identified by 18 hr following injection, and expression was still detectable after 2 weeks. All animals survived with no behavioral, gross, or microscopic anatomical evidence of a virulent neurologic infection.