| abstract |
A mutant of the herpes simplex virus type 1 (HSV-1) capable of establishing a latent infection in the absence of viral replication in vivo in neuronal cells and capable of expressing an inserted therapeutic gene consists : (i) a change in DNA sequence in the gene coding for the protein Vmw65, capable of substantially canceling the transinduction properties while retaining its structural role and thus preventing replication in vivo, the change of DNA sequence being produced by modifying the transition or transversion from 1 to 72 base pairs, the insertion of oligonucleotide into 3 to 72 base pairs, or the deletion of 3 to 72 base pairs, to a position between amino acids 289 and 412 of the protein; (ii) a therapeutic gene inserted into a region of the HSV-1 genome which is not essential for the culture of the virus, and a promoter thus capable of expressing the therapeutic gene in neuronal cells in vivo. The preferred insertion site for the therapeutic gene (e.g., the tirosine hydroxylase gene) is in the thymidine kinase gene of HSV in 1814. |