Viral vectors and their use in therapeutic methods
The invention provides viral vectors (e.g., herpes viral vectors) and methods of using these vectors to treat disease.
1. A herpes simplex virus-1 (HSV-1) comprising an inactivating mutation in the ICP47 locus of the virus, wherein said mutation occurs between the BstEII site and the EcoNI site of the BamH1 fragment encompassing the ICP47 region, and said mutation places US11 under control of the ICP47 immediate-early promoter, said virus further comprising one or more additional mutations selected from the group consisting of an inactivating mutation in the γ34.5 neurovirulence determination locus and an inactivating mutation in the ICP6 locus.
2. A herpes simplex virus-1 (HSV-1) comprising an inactivating mutation in the ICP47 locus of the virus, wherein said mutation occurs between the BstEII site and the EcoNI site of the BamH1 fragment encompassing the ICP47 region, and said mutation places US11 under control of the ICP47 immediate-early promoter, said virus further comprising an inactivating mutation in the γ34.5 neurovirulence locus of said virus and an inactivating mutation in the ICP6 locus of said virus.
3. A pharmaceutical composition comprising the virus of claim 2 and a pharmaceutically acceptable carrier, adjuvant, or diluent.
4. A herpes simplex virus-1 (HSV-1) comprising a deletion, wherein said deletion comprises the region between the BstEII site and the EcoNI site of the BamH1 fragment encompassing the ICP47 region and the deletion places US11 under control of the ICP47 immediate-early promoter, said virus further comprising one or more additional mutations selected from the group consisting of an inactivating mutation in the γ34.5 neurovirulence determination locus and an inactivating mutation in the ICP6 locus.
5. A pharmaceutical composition comprising the virus of claim 4 and a pharmaceutically acceptable carrier, adjuvant, or diluent.