This project seeks to establish a protocol to deliver a class of engineered proteinaceous inhibitors, called ubiquitin variants (UbVs), that are specific to deubiquitinases (including USP8), using vesicular stomatitis virus G (VSV-G) glycoprotein-based virus-like particles (VLPs) to validate the therapeutic potential of targeting the ubiquitination-EGFR pathway in GBM. Ubiquitination is a novel pathway to target for GBM treatment. We expect our VSV-G-based vesicles will efficiently cross the blood-brain barrier and deliver the UbVs into GBM cells. The target-specific and potent UbVs will block different GBM cell signaling pathways.