Upregulaton of HSV TK Gene & Brain Cancer Gene Therapy

We will test the capacity to increase tumor cell killing by introducing the herpes simplex virus (Hkinase (TK) gene on a retroviral vector and treating with ganciclovir (GCV). Our approach is to consthat can be upregulated to express elevated levels of HSV thymidine kinase. We will use glucocorticotransactivator systemss to direct transcription of HSV TK gene from a target promoter element, as weretrovirus LTR. The ability to upregulate HSV TK gene expression will be evaluated in vitro by measuprotein to determine that transcription, translation, and enzymatic activity can be increased in resThe effect of increasing thymidine kinase levels on the IC-50 of GCV will be assessed in rat 9L gliodetermine if increased thymidine kinase levels can increase the efficacy of GCV tumor cell killing.the "bystander effect" will be assessed in vitro in rat 9L glioma cells to determine if higher thymiincrease the number of untransduced neighboring tumor cells that are killed by a tk+ transduced tumo