Date of Award

Spring 2022

Document Type

Thesis

Publisher

Santa Clara : Santa Clara University, 2022.

Department

Bioengineering

First Advisor

Bill Lu

Abstract

Exosomes, a class of extracellular vesicles (EVs) are emerging as a new scientific and therapeutic tool for imaging, disease diagnostics, and drug delivery. Exosomes' excellent biological properties make them a strong candidate for surface modification as well as exogenous drug loading. While exosomes have excellent natural biocompatibility properties as well as low immunogenicity, they are still eliminated in the patient’s body through the immune system, mainly through phagocytosis by macrophages. In this report, we aim to aid exosomes in avoiding this elimination method by modifying them through surface display with antiphagocytic factors. We will use CD24 and CD47 “don't eat me signals” that have been identified as key mediators of macrophage phagocytosis and apply chemical transfection to target them to the exosome pathway. We also test a tVSVG scaffold to boost the membrane targeting potential of these two proteins to increase the density of CD24 or CD47 proteins on the exosomal surface. Once we have successfully modified cells, we will perform exosome harvest to isolate modified exosomes and analyze them for CD24 and CD47 expression. This project represents the first step in the generation of an immunoevasive exosomal drug delivery platform.

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