A DEFECTIVE HERPES-SIMPLEX VIRUS VECTOR SYSTEM FOR GENE DELIVERY INTOTHE BRAIN - COMPARISON WITH ALTERNATIVE GENE DELIVERY SYSTEMS AND USEFULNESS FOR GENE-THERAPY

The delivery of exogenous genes into the brain is becoming an increasi ngly important strategy for answering questions about the molecular me chanisms of brain function. Answers to these questions may be applied to many of the disorders that affect the brain. For example, a detaile d understanding of the mechanisms that modulate longterm changes in ne urotransmitter release will almost certainly lead to new approaches to diseases such as the epilepsies, in which neurotransmitter release is altered. Knowledge of the molecular means by which neurotransmitters shape neuronal development and cause neurodegeneration, or of how trop hic factors regulate neuronal health, will lead to insights into how d efects in these pathways cause specific diseases. To answer these ques tions, we have developed a defective herpes simplex virus (HSV) system for the delivery of exogenous genes into the brain. This system direc ts precise spatial and temporal expression of recombinant genes in the brain. We discuss its utility in comparison to other methods of gene transfer into the brain for answering basic questions about the molecu lar basis for neuronal physiology and for gene therapy. (C) 1996 Wiley -Liss, Inc.