Protein Nanoparticles For Applications In Chemical Biology And Immunology
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Hincapie, Robert
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Abstract
Throughout this thesis, I leverage the properties of virus-like particles (VLPs) – their highly organized structure, immunogenicity, optimal size for trafficking to lymph nodes, their ability to undergo dense surface chemical modification, and overall stability– to produce a series of targeted platforms for cellular targeting, imaging, and vaccinology. The copper(I)-catalyzed azide-alkyne cycloaddition is used to direct surface modification of VLPs with ligands that imbue the resulting particles with selected functional properties. Multivalent carbohydrate ligands are used to direct selective uptake of particles in hepatic cells in vitro or in vivo; oligonucleotide ligands are used to generate VLP-spherical nucleic acids, with enhanced non-specific uptake properties and reduced immunogenicity in vivo; pathogen-associated carbohydrate antigens are displayed on VLPs towards the development of potent monoclonal antibodies; finally, multifunctional particles bearing dendritic cell-targeting glycan ligands and model peptide antigens are used as potent immunogens to generate antigen-specific cellular immunity. The collaborative and interdisciplinary projects described within this thesis compliment previous work towards the manipulation and engineering of protein nanoparticles, and provide several starting points for further efforts.
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2022-09-02
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Dissertation