Biophysical and biochemical characterization of an HBV cccDNA g-quadruplex targeting therapeutic

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dc.contributor.authorBalderas Figueroa, Gerardo K.
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorPatel, Trushar R.
dc.date.accessioned2023-09-26T17:37:19Z
dc.date.available2023-09-26T17:37:19Z
dc.date.issued2023
dc.degree.levelMasters
dc.description.abstractHepatitis B virus (HBV) has chronically infected 296 million people, and it is the leading cause of cirrhosis and hepatocellular carcinoma (HCC). Current treatments target post-transcriptional steps of the viral cycle, which leaves HBV’s covalently closed circular DNA (cccDNA) nuclear reservoirs unaffected. This allows patients to relapse if therapy ceases. We have previously identified a G-quadruplex (G4) forming region in the HBV preCore promoter involved in viral replication. Here, we develop recombinant single-domain antibodies (sdAbs) that can target this G4-forming region. The sdAbs are purified by chromatography, and their interaction with HBV G4 is characterized by biochemical binding assays as well as biophysical techniques. We conclude that sdAbs can be highly structure and sequence specific towards HBV G4. Overall, my work develops a pipeline for G4-targeting that can be used in future HBV cccDNA studies as well as be implemented in the study of other G4s involved in disease.
dc.identifier.urihttps://hdl.handle.net/10133/6587
dc.language.isoen
dc.proquest.subject0786
dc.proquest.subject0487
dc.proquestyesYes
dc.publisherLethbridge, Alta. : University of Lethbridge, Dept. of Biochemistry and Chemistry
dc.publisher.departmentDepartment of Biochemistry and Chemistry
dc.publisher.facultyArts and Science
dc.relation.ispartofseriesThesis (University of Lethbridge. Faculty of Arts and Science)
dc.subjectHBV
dc.subjectCovalently closed circular DNA
dc.subjectcccDNA
dc.subjectG-quadruplex
dc.subjectG4
dc.subjectSingle-domain antibodies
dc.subjectsdABs
dc.subject.lcshHepatitus B virus
dc.subject.lcshDissertations, Academic
dc.titleBiophysical and biochemical characterization of an HBV cccDNA g-quadruplex targeting therapeutic
dc.typeThesis
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