There are ~20,000 cases per year of glioblastoma in the U.S., and median survival time is only 15 months. The integration of two technologies to create an optimized oncolytic virus for glioblastoma is proposed. The resulting virus is triply armed: (1) it has a clinically proven mechanism and enhanced abilities to evade the immune system;(2) it disrupts the physical barrier between glioblastoma cells in a tumor, enhancing viral spread;(3) it expresses GM-CSF to enhance anti-cancer immunity. At the end of this work, it will be determined if the lead virus has potential in the treatment of glioblastoma. The next steps would be to move it through the necessary preclinical studies required to file an IND with the FDA and begin clinical studies. The market for glioblastoma is estimated at $449M, providing significant upside to the successful development of a new treatment. Glioblastoma has a very poor prognosis, and new therapies are desperately needed. The treatment proposed to be developed could enhance survival and quality of life for these patients.