Browsing by Subject "G-quadruplex"

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    Development and characterization of aptamer-amphiphiles against fractalkine for targeted drug delivery
    (2013-12) Waybrant, Brett M.
    A foundation of modern diagnostics and therapeutics is the ability to non-covalently bind to a molecule of interest. These affinity molecules are behind a broad array of products ranging from therapeutics to HIV tests. Currently, antibodies are used as the affinity molecule. Despite the success of antibodies, alternatives are needed due to high development and production costs, and issues with stability. Aptamers are an exciting alternative to antibodies. Aptamers are short sequences of single stranded DNA or RNA that bind molecular targets with high affinity and specificity. Aptamers are inexpensive to produce, are very stable, have long shelf lives, and could potentially replace antibodies in a number of applications. One potential application of aptamers is targeted drug delivery. The goal of targeted drug delivery is to selectively deliver a therapeutic payload to the site of action thereby increasing efficacy and decreasing side effects. Fractalkine is a cell surface protein expressed at sites of inflammation. It is expressed on several types of cancerous tissues and it is involved in the patheogenisis of arthritis, asthma, and atherosclerosis. This work describes the development and characterization of an aptamer that binds fractalkine with high affinity. The aptamer was modified with a hydrophobic tail, creating an aptamer-amphiphile, for use in a model drug delivery vesicle called a liposome. The aptamer-amphiphile was optimized for a high affinity interaction with fractalkine by adding a spacer molecule between the aptamer headgroup and the hydrophobic tail. The optimized amphiphile had high affinity for fractalkine and self-assembled into micelles and an interesting nanotape morphology. Finally, as a proof of concept, the optimized aptamer-amphiphile was incorporated into a liposome and targeted to fractalkine expressing cells. This work highlights the development of aptamers as affinity ligands, and demonstrates their use as potential drug delivery agents.
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    Exploiting Chaotropic Salt-Nucleic Acid Interactions for Biotechnology and Understanding the Origins of Life
    (2023-12) Hoog, Tanner
    The dynamic nature of nucleic acid structures is pivotal for dictating function and maintaining homeostasis, with environmental factors playing a significant role in controlling conformational integrity. Ions are a valuable means of assessing structural stability due to their dual mode of action: modulating water activity and directly interacting with biopolymers. In this dissertation, the strong chaotropic anion perchlorate emphasized a significant stability difference between the G-quadruplex secondary structure and the canonical double helix. This allowed for the rational design of extremely salt-resistant DNA-based biosensors tunable via concentration or dilution. The structural stability of nucleic acid polymers is also recognized through the endurance of ribozymes to maintain activity in chaotropic extraterrestrial brines, such as those found on Mars, supporting the idea that RNA can bridge the gap between prebiotic chemistry and cellular life. Together, this body of work contributes to the fundamental understanding of biomolecular stability in the context of both past and present life and the practical utility of understanding the underlying mechanisms.