Vectors derived from herpes simplex virus provide a means of gene delivery to 
postmitotic neurons. The virus is readily taken up at nerve terminals, passes by 
rapid retrograde and anterograde transport within neurons, and is selectively 
transferred across synapses, thus allowing it entry from the periphery into the 
brain. This virus can enter a state of latency in some neurons, where it exists 
as an episomal element in the nucleus and is transcriptionally active to a 
reduced extent. In this state, the virus is apparently benign and can effect 
stable expression of foreign genes. The large (150 kb) genome of this 
double-stranded virus has been completely sequenced. Many of its 70 genes can be 
replaced while still allowing the virus to replicate in at least some cultured 
cells. Some mutations in the viral genome can compromise the toxicity of the 
virus and reduce or eliminate its ability to replicate within neurons. Many uses 
for herpes vectors can be envisioned, including evaluation of neuronal promoter 
elements and functions of neural proteins in culture and in vivo, as well as 
therapeutic delivery of genes to modulate nerve function and for gene 
replacement therapy in vivo.