Replication-competent controlled alpha-herpesvirus vectors and uses therefore
AssigneeHSF Pharmaceuticals SA
InventorRichard W Voellmy
Life of this patent
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Abstract
The present disclosure relates to replication-competent controlled herpesviruses whose transient replication in a desired inoculation site region of a subject can be activated by the delivery of an appropriate heat dose to the inoculation site region. In related recombinant viruses, activation requires delivery of a heat dose in the presence in the inoculation site region of an effective concentration of a small-molecule regulator. The viruses are further engineered to be capable of replicating efficiently in the desired inoculation site region but essentially not in nerve ganglia and other nerve cells.
Claims12
A heat-controlled or heat- and small-molecule regulators-controlled replication-competent controlled alpha-herpesvirus whose replication can be transiently activated in nonneural cells infected with said replication-competent controlled alpha-herpesvirus but that cannot be transiently activated in neural cells infected with said replication-competent controlled alpha-herpesvirus, wherein the replication-competent controlled alpha-herpesvirus is a recombinant alpha-herpesvirus derived from a virus of the group consisting of a herpes simplex virus type 1 (HSV-1), a herpes simplex virus type 2 (HSV-2) and a varicella-zoster virus, said replication-competent controlled alpha-herpesvirus comprising:
- (a) a first heterologous promoter that is a nucleic acid sequence that acts as a heat shock promoter, the first heterologous promoter controlling the expression of a first replication-essential gene of the replication-competent controlled alpha-herpesvirus, wherein
- (1) the first heterologous promoter is functionally linked to the first replication-essential gene of the replication-competent controlled alpha-herpesvirus, or
- (2) the first heterologous promoter is functionally linked to a gene for a heterologous, unregulated or small-molecule-regulated transactivator that has been inserted in the genome of the replication-competent controlled alpha-herpesvirus and the first replication-essential gene is functionally linked to a promoter that is responsive to the transactivator, and
- (b) a second heterologous promoter that is known to be active in nonneural cells of a mammalian subject to which the replication-competent controlled alpha-herpesvirus is to be administered but is also known to be essentially inactive in neural cells of the mammalian subject, the second heterologous promoter being functionally linked to a second replication-essential gene of the replication-competent controlled alpha-herpesvirus.
Dependencies are inferred from the claim text.