A recombinant lytic virus transcriptionally targeted against malignant cells. A promoter for a viral gene controlling replication is replaced with a promoter for a malignant factor such that the promoter for the malignant factor controls expression of the viral gene controlling replication. Accordingly, the recombinant lytic virus of the present invention only replicates within and kills cells expressing the malignant factor. In an embodiment, the recombinant lytic virus is a recombinant herpes simplex virus, and the viral gene controlling replication is a herpes alpha gene. In an embodiment, the recombinant lytic virus is transcriptionally targeted against cancer stem cells (CSCs). In an embodiment, the recombinant lytic virus is a recombinant herpes simplex virus-1 (HSV-1) with the promoter of CD133 controlling the expression of infected cell protein-4 (ICP4). In another embodiment, the recombinant lytic virus is a recombinant HSV-1 with the promoter of Ezh2 controlling the expression of ICP4.