Herpes simplex virus vectors for gene transfer to the nervous system.

Herpes simplex virus (HSV) represents a candidate gene transfer vector for the treatment of nervous system disease. It has many natural biological features which make it attractive for gene delivery to a variety of tissues. The virus naturally establishes a latency in sensory neurons of the peripheral nervous system, wherein the virus in maintained as an extrachromosomal DNA element in the absence of viral lytic gene expression without altering the metabolism of the host neuron. The virus possesses a neuronal latency-specific promoter system which remains active long-term, while other viral and cellular promoters are repressed. Replication defective virus recombinants have been engineered to delete multiple essential immediate early gene functions rendering these new mutants significantly less cytotoxic to neurons and other cells in culture. Further developments in regulating transgene expression and reducing virus toxicity will continue to aid the design and use of these vectors for therapeutic applications for the nervous system.