Viral vectors whose replication and, optionally, passenger gene are controlled by a gene switch activated by heat in the presence or absence of a small-molecule regulator

A conditionally replicating pair of modified viruses consisting of (a) a first virus that is defective in one or more genes required for efficient replication and whose genome includes a gene for a small-molecule-regulated transactivator, the gene for the small-molecule-regulated transactivator being functionally linked to a nucleic acid sequence that acts as a heat shock promoter, and (b) a second virus comprising all genes required for efficient replication of which genes at least one gene is under the control of a promoter that is responsive to the small molecule-regulated transactivator of the first virus and is not complemented by a functional gene of the first virus, wherein expression of all genes of the second virus required for its replication will complement the defects of the first virus and result in its replication, with the proviso that first and second viruses belong to the same species, except that if the second virus is an adenovirus, the first virus can be an adeno-associated virus.