Herpes simplex virus for gene delivery to neurons.

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.