Beyond antibodies : high-throughput technologies for the development of synthetic affinity reagents with novel functions
- The accurate measurement of molecules is of crucial importance for a wide range of both basic and applied research applications. In particular, we need to measure the abundances and activities of biomolecules (proteins, carbohydrates, lipids, and nucleic acids) to understand their biological function which form the basis of life and diseases. To this end, we rely on affinity reagents, which are molecules that specifically bind to their target molecule. While antibodies are the current 'gold standard' of affinity reagents, there is a growing need for alternative reagents. Aptamers, often referred to as chemical antibodies, are short oligonucleotides that can bind to their targets with high specificity and affinity and can be engineered to perform novel functions that cannot be achieved with conventional antibodies. In this dissertation, I will discuss the development of three high-throughput technologies that enable the creation of synthetic DNA aptamers with novel functions. The first project describes a method to generate base-modified aptamers that can recognize protein glycoforms with exquisite specificity, which is challenging for antibodies. The second project describes the creation of a massively-parallel screen which enables the multiplexed selection of aptamers with extraordinary specificity that can distinguish metabolites with minimal difference in their chemical structure. Finally, I describe a screening technology for rapidly generating optically-responsive molecular switches from an existing aptamer which can be used directly as biosensors. As a whole, these studies provide valuable new tools that help address many of the challenges associated with the development of aptamers that are suitable for real-world applications.
|Type of resource
|electronic resource; remote; computer; online resource
|1 online resource.
|Yoshikawa, Alexander Masao
|Soh, H. Tom
|Soh, H. Tom
|Degree committee member
|Stanford University, Department of Chemical Engineering
|Statement of responsibility
|Alexander Masao Yoshikawa.
|Submitted to the Department of Chemical Engineering.
|Thesis Ph.D. Stanford University 2021.
- © 2021 by Alexander Masao Yoshikawa
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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