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Fluorescent Tools for Bioimaging & Industrial Process Development of Antibody-Drug Conjugates
Fluorescence-based tools have revolutionized fundamental and applied research. Fluorescent tools and techniques facilitate the drug discovery and development processes at various stages. Chapter 2 and 3 of this work are centered around the industrial process development of antibody-drug conjugates, which are well-established anticancer therapeutics. The specificity of the monoclonal antibodies towards cancer-cell surface antigen combined with the high potency of small-molecule drugs in an ADC presents them as highly promising targeted therapeutics for cancer. They are envisioned to grow rapidly in the next decade with numerous advancements in development of superior conjugation technologies. However, the technical challenges and complexities associated with manufacturing of antibody-drug conjugates impede these developments. This work aims to address the barriers associated with hazardous ADC components and presents a solution for expanding the ADC research in a safer and less-expensive way. Specifically, fluorescent non-toxic surrogates of the most prominent warheads are designed to mimic the physicochemical properties of the ADCs and facilitate their process development. Chapter 4 is focused on the fluorescent peptide nucleic acids as FISH probes to label telomere-repeat containing RNA (TERRA). TERRA is known to play a key role in alternative lengthening of telomeres in ALT-positive cancer cells with low expression of telomerase enzyme. However, the exact mechanisms and associated functions are unknown. The FISH PNA probes are shown to successfully label TERRA and have potential application in live-cell imaging.
History
Date
2024-08-01Degree Type
- Dissertation
Department
- Chemistry
Degree Name
- Doctor of Philosophy (PhD)