We propose to develop a non-viral cancer gene therapy approach for treatment of brain tumors. The research plan is to first show that the tumor vasculature can be transfected with a cationic lipid/plasmid-based transfection complex. Two methods for administration will be tested. These are: systemic administration by tail vein and intra-carotid administration by catheter. Delivery will be evaluated by quantitation of plasmid uptake, demonstration of tumor vasculature uptake by fluorescence microscopy and quantifying the amount of gene expression. Criteria for evaluation of the two administration routes is the effective dose yielding maximal expression. The administration route and optimal dose will then be used to test anti-angiogenic genes for their ability to reduce tumor vessel density, inhibit tumor growth and ultimately increase survival times. PROPOSED COMMERCIAL APPLICATIONS: Currently, the prognosis for patients with malignant brain tumors is grim, with a median survival of 9-10 months from glioblastomas. Approximately, 170,000 cases of brain tumors (primary and metastasized) occur each year in the United States. Surgical ablation and radiation results in numerous problems. Pharmaceutical therapies have faced substantial problems due to inherent challenge of crossing the blood brain barrier. There is compelling need for effective treatment strategies.
