Date of Award

6-2025

Document Type

Thesis - SCU Access Only

Publisher

Santa Clara : Santa Clara University, 2025

Department

Bioengineering

First Advisor

Bill Lu

Abstract

The objective of our project is to test the efficacy of delivering an engineered suicide gene to cancer cells and spreading the produced enzyme to neighboring cancer cells via extracellular vesicles, in particular exosomes, for targeted prodrug therapy. Our project focuses specifically on glioblastoma brain cancer, a highly aggressive and malignant form of cancer with very few effective treatment options. Current therapy options are either very dangerous, as is the case with surgery, or affect the entire body, as is the case with chemotherapy. Suicide gene-derived enzyme prodrug therapy is safe targeted method that has the capability to treat brain cancer, but has a few limitations. Our project aims to overcome these limitations by localizing the suicide gene enzyme in the lumen of exosomes, which will facilitate the delivery of the enzyme to uninfected cells. We will first establish stable cell lines to produce therapeutic exosomes, then harvest the exosomes for characterization and functionality testing. We will similarly confirm the presence of our therapeutic enzyme at each step through fluorescent labeling. The successful localization and spread of the engineered enzyme by exosome-mediated delivery will allow for the effect of the suicide gene and prodrug therapy to occur throughout the tumor, increasing its effectiveness in treating the cancer. This novel therapy is targeted at glioblastoma patients, although it is applicable with other forms of cancer. Successful treatment may help improve prognosis and increase the survival rate in glioblastoma patients. Ethical considerations, including cost, safety, and accessibility, will be considered throughout the design process.

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