THE USE OF HERPES-SIMPLEX VIRUS VECTORS FOR GENE-THERAPY IN NEUROLOGICAL DISEASES

Herpes simplex virus type 1 (HSV-1) vectors have now been developed an d enable the efficient delivery of foreign genes under the control of appropriate promoter elements into non-dividing neurons in vitro and i n vivo. Their use is based on the natural ability of HSV-1 to spread t hroughout the nervous system and to establish a lifelong latent infect ion in neurons. HSV is present in an episomal form in the neuronal nuc leus, and normal neuronal functions remain unaltered. A wide variety o f foreign genes can theoretically be packaged into the large HSV genom e. A number of technical problems will need to be overcome to ensure t he stable expression of the foreign gene products, adequate control of the levels of their expression, the safety of the vectors and the cor rect targeting of the vectors to the appropriate neuronal cell populat ions. Such vectors have the potential to replace missing gene products in neurons in patients with a variety of metabolic and neurodegenerat ive diseases, and also to insert growth factors or enzymes into the lo cal vicinity of neurological lesions to promote neuronal repair. HSV-1 vectors also have the potential to define the genetic basis of variou s neurophysiological functions which may prove to be useful in evaluat ing altered neuronal function encountered in disease.