Optimizing gene delivery for an early cancer detection strategy

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Abstract/Contents

Abstract
Many forms of advanced cancer remain difficult to treat, with tremendous economic and social costs. Early cancer detection holds great potential in reducing cancer mortality, with the benefits of screening already well-recognized and implemented for several cancer types, including skin, colon, and breast cancers. Meanwhile, sensitive and specific screening methods for deep-tissue, aggressive cancers such as ovarian, lung, and pancreatic cancers remain elusive. Because these cancers are located far from a surface that can be easily probed, minimally invasive methods involving blood biomarkers and imaging offer great possibilities. In this thesis, I introduce a novel two-step strategy for detecting cancer early that depends on delivery of a minicircle DNA molecular probe to a tumor. In Chapter 2, I show proof-of-concept that a secretable blood biomarker and Positron Emission Tomography (PET) imaging reporter gene can be encoded on a tumor-activatable minicircle and delivered via a cationic transfection reagent. In animal studies, the secretable blood biomarker can be detected in the blood of tumor-bearing mice compared to healthy mice, and PET reporter gene expression can be quantified at significant levels in tumors. This highlights the potential of tumor-activatable minicircles to deliver reporter genes for an early cancer detection strategy. However, improved delivery vehicles for the minicircles would benefit the strategy. In Chapter 3, I investigate the ability of extracellular vesicles to encapsulate and deliver minicircles, and in Chapter 4, I expand the toolbox of delivery vehicles to include ionizable lipid nanoparticles. Novel strategies for early cancer detection combined with more targeted tumor delivery holds great potential in reducing cancer mortality.

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2021; ©2021
Publication date 2021; 2021
Issuance monographic
Language English

Creators/Contributors

Author Robinson, Elise Rose
Degree supervisor Ferrara, Katherine
Thesis advisor Ferrara, Katherine
Thesis advisor Lee, Jin Hyung
Thesis advisor Paulmurugan, Ramasamy
Degree committee member Lee, Jin Hyung
Degree committee member Paulmurugan, Ramasamy
Associated with Stanford University, Department of Bioengineering

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Elise Robinson.
Note Submitted to the Department of Bioengineering.
Thesis Thesis Ph.D. Stanford University 2021.
Location https://purl.stanford.edu/cy036rf6683

Access conditions

Copyright
© 2021 by Elise Rose Robinson
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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