HERPES-SIMPLEX VIRUS VECTORS FOR GENE-THERAPY

A number of different viruses have been proposed as potential vectors for gene delivery to the nervous system. Herpes simplexvirus (HSV) has particular advantages in this regard since it establishes life long a symptomatic infections of the nervous systems and has a large genome s ize capable of accepting large amounts of foreign DNA. Two methods of using HSV-based vectors in gene delivery have been proposed. These inv olve either the insertion of the foreign gene directly into the virus to create a recombinant virus or its insertion into an amplicon plasmi d vector which contains an HSV origin of replication and packaging sig nal and which requires a helper HSV virus in order to be propagated. I n both cases, it is necessary to disable either the recombinant virus itself or the helper virus to prevent damaging effects due to lytic re plication by the virus whilst maintaining the efficiency of gene deliv ery. This disabling process is one of the major challenges still to be overcome before HSV-based vectors can be used in clinical therapy, th e over being the development of means to ensure that the foreign gene is expressed in the long term after the virus has entered latency. The potential means of overcoming these problems and the potential use of HSV-based vectors in a number of different situations are discussed.