Full metadata
Title
Membrane Modulating DNA Nanostructures for Diagnostics and Immunotherapeutics
Description
The biological lipid bilayer on cells or the cell membrane is a surface teeming with activity. Several membrane proteins decorate the lipid bilayer to carry out various functionalities that help a cell interact with the environment, gather resources and communicate with other cells. This provides a repertoire of biological structures and processes that can be mimicked and manipulated. Since its inception in the late 20th century deoxyribonucleic acid (DNA) nanotechnology has been used to create nanoscale objects that can be used for such purposes. Using DNA as the building material provides the user with a programmable and functionalizable tool box to design and demonstrate these ideas. In this dissertation, I describe various DNA nanostructures that can insert or interact with lipid bilayers for cargo transport, diagnostics and therapeutics. First, I describe a reversibly gated DNA nanopore of 20.4nm x 20.4nm cross sectional width. Controlled transport of cargoes of various sizes across a lipid bilayer through a channel formed by the DNA nanopore was demonstrated. This demonstration paves the way for a class of nanopores that can be activated by different stimuli. The membrane insertion capability of the DNA nanopore is further utilized to design a nanopore sensor that can detect oligonucleotides of a specific s equence inside a lipid vesicle. The ease with which the sensor can be modified to i dentify different diagnostic markers for disease detection was shown by designing a sensor that can identify the non small cell lung cancer marker micro ribonucleic acid -21 (miRNA21). Finally, I demonstrate the therapeutic capabilities of DNA devices with a DNA tetrabody that can recruit natural killer cells (NK cells) to target cancer cells. The DNA tetrabody functionalized with cholesterol molecules and Her2 affibody inserts into NK cell membrane leading it to Her2 positive cancer cells. This shows that inthe presence of DNA tetrabody, the NK cell activation gets accelerated.
Date Created
2023
Contributors
- Abraham, Leeza (Author)
- Yan, Hao (Thesis advisor)
- Liu, Uan (Committee member)
- Stephanopoulos, Nicholas (Committee member)
- Arizona State University (Publisher)
Topical Subject
Resource Type
Extent
173 pages
Language
eng
Copyright Statement
In Copyright
Primary Member of
Peer-reviewed
No
Open Access
No
Handle
https://hdl.handle.net/2286/R.2.N.189233
Level of coding
minimal
Cataloging Standards
Note
Partial requirement for: Ph.D., Arizona State University, 2023
Field of study: Chemistry
System Created
- 2023-08-28 04:47:56
System Modified
- 2023-08-28 04:48:10
- 1 year 2 months ago
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