HERPES SIMPLEX VIRUS TYPE 1 MUTANT

• Main Authors: CHRISTOPHER IAN ACE, CHRISTOPHER MAURICE PRESTON
• Format: Patent
• Language: English
• Published: 03.04.1991
• Edition: 5
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS THEREOF; CULTURE MEDIA; ENZYMOLOGY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MUTATION OR GENETIC ENGINEERING; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS; SPIRITS; VINEGAR; WINE

A herpes simplex virus type I (HSV-1) mutant capable of establishing latent infection in the absence of in vivo viral replication in neuronal cells and of expressing an inserted therapeutic gene, which comprising: (i) a DNA sequence change in the gene coding for Vmw65 protein, such as to substantially remove the transducing properties while retaining its structural role and thereby preventing in vivo replication, the DNA sequence change being achieved by a transition or transversion alteration of 1 to 72 base pairs, an oligonucleotide insert of 3 to 72 base pairs, or a deletion of 3 to 72 base pairs, at a position between amino acids 289 and 412 of the protein; and (ii) a therapeutic gene inserted into a region of the HSV-1 genome which is non-essential for culture of the virus, and a promoter therefor able to express the therapeutic gene in neuronal cells in vivo. The preferred insertion site for the therapeutic gene (e.g. tyrosine hydroxylase gene) is within the thymidine kinase gene of HSV in 1814.