Delivery of Herpes Simplex Virus-Based Vectors to the Nervous System

Gene transfer to the nervous system is an attractive option to treat a wide variety of neurological insults (1 –3 ). The expression of trophic factor and/or antiapoptotic genes may be beneficial in halting the slow neurodegeneration in such conditions as Parkinson’s disease (4 ,5 ), the rapid neuronal cell death following trauma to the brain or spinal cord (6 ,7 ), or in treating peripheral neuropathies associated with diabetes or use of chemotherapeutic agents (8 ,9 s). Introduction of dominant-negative mutant genes or antisense RNA to treat diseases such as Huntington’s disease (10 ), or transfer of genes to replace lost or mutated endogenous proteins to treat disorders such as lysosomal storage diseases (11 ), may prove useful. In addition, gene transfer to overexpress endogenous antinociceptive proteins has great potential in pain management (12 ). The problem faced by all of these applications is finding a suitable methodology that will facilitate the transfer of exogenous genes to the appropriate nerve cells; virus-based vectors have proven quite efficient in transferring genes to many different cell types (13 ).