Potential use of herpes simplex virus (HSV) vectors for gene therapy of neurological disorders.

Abstract

Advances in molecular biology and virus genetics have allowed the possibility of gene therapy using viral vectors for a variety of neurological diseases in which the genetic or biochemical basis is understood. A number of such vectors have now been constructed, including those derived from herpes simplex virus (HSV), adenovirus, retrovirus and adeno-associated virus, and used in preliminary in vitro experiments and in animal models. It is possible to package a foreign gene into such a vector which can then be targeted to specific regions of the nervous system. HSV is particularly appropriate for delivering genes to neurons in view of its ability to establish latent infection in these cells. Viral vectors have the potential to be used to treat such neurological conditions as malignant gliomas, Parkinson's disease, known single gene disorders and cerebral ischaemia. However, the technical problems which will need to be overcome are formidable and will not be easily solved. The problems include the efficient delivery of the vector to target cells, the maintenance and control of foreign gene expression, and the control of unwanted host immune responses.