Keywords and Phrases
DNA origami; Doxorubicin; Gene delivery; Gene editing; Triple negative breast cancer; Uptake
"A review of gene delivery methods and gene editing methods, as well as original research utilizing DNA as a delivery vehicle is presented in the following thesis. Thousands of diseases have been linked to genes. Gene therapy, either delivering therapeutic genes or editing DNA bases, has arisen as a treatment option with the potential to cure diseases, rather than just ease symptoms. Genes and editing tools need to be delivered to cells for these therapies to be effective and many techniques have been developed to address the issue of delivery. Nonviral and viral methods have been used to deliver nucleic acids and several different protein systems have been employed to edit genes. Gene therapy will continue to evolve as delivery are improved. Along with being delivered as a therapeutic molecule, DNA has been investigated as a carrier itself. DNA origami, have been utilized to deliver chemotherapies to breast cancer. Globally, millions of women are affected by breast cancer each year. DNA origami was analyzed as a carrier for the chemotherapy Doxorubicin (DOX) in two triple negative breast cancer (TNBC) cell lines, a type of breast cancer with few treatments. The killing efficiency and uptake of DOX loaded into a model DNA origami triangle (DOX-DNA-T) were elucidated. Inhibition of various pathways revealed DOX-DNA-T was internalization by multiple energy-dependent pathways. DOX-DNA-T altered the subcellular localization of DOX and increased the concentration of DOX inside cells. A delayed killing was observed with DOX-DNA-T compared to free DOX, but the carrier was able to modulate the toxicity between cell lines. Overall, DNA delivery is able to treat various disease conditions and DNA origami is an interesting carrier for therapeutics"--Abstract, page iv.
M.S. in Applied and Environmental Biology
Center for Research in Energy and Environment (CREE)
Missouri University of Science and Technology
Journal article titles appearing in thesis/dissertation
- Evolutionary Timeline of Genetic Delivery and Gene Therapy
- DOX-loaded DNA Origami Triangle Uptake and Cytotoxic Effects in Triple Negative Breast Cancer Cell Lines
xiv, 122 pages
© 2020 Natalie Jordan Holl, All rights reserved.
Thesis - Open Access
Holl, Natalie J., "Therapeutic DNA: Delivery and as a delivery vehicle" (2020). Masters Theses. 7965.