Date of Award
Spring 2023
Document Type
Open Access Dissertation
Department
Chemistry and Biochemistry
First Advisor
Qian Wang
Abstract
Oncolytic virus (OV) therapy has been shown to be an effective targeted cancer therapy treatment in recent years, providing an avenue of treatment that poses no damage to surrounding healthy tissues. Not only do OVs cause direct oncolysis, but they also amplify both innate and adaptive immune responses generating long-term antitumor immunity. However, a key challenge facing oncolytic virotherapy is neutralizing antibodies in vaccinated patients, leading to the viral clearance after systemic administration and failure in the treatment. The encapsulation of OVs using biocompatible polymers is one of the promising methods to prevent the viral clearance from antiviral immune responses. This dissertation focuses on the development of stimulus-responsive viral delivery platform by employing polymers to modulate viral infectivity via surface conjugations. The modification of viral envelope can be achieved by hijacking the intrinsic phospholipid biosynthesis of host cells to incorporate special functional groups. We metabolically labeled enveloped viruses, vaccinia virus and measles virus, with choline analog, azidoethyl-choline (AECho). The azide functionalized virus can further react readily with alkyne containing compounds via click chemistry. The first new design of PEGylated virus with acid- and matrix metalloproteinases-cleavable linkers was also proposed in this dissertation. Moreover, we investigated phenylboronic acid functionalized polymer and its ability to block the viral entry via forming multivalent interactions with cis-diols on the glycans of glycosylated viral envelope. Finally, cellular responses to nanoscale substrate topography of TiO2 nanotube arrays was also discussed.
Rights
© 2023, Monchupa Kingsak
Recommended Citation
Kingsak, M.(2023). Vaccinia Virus and Measles Virus as Oncolytic Vaccines: The Modulation of the Viral Infectivity via Surface Conjugations. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/7167