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dc.contributor.advisorMcMillan, Nigel
dc.contributor.authorTayyar, Yaman A
dc.date.accessioned2021-10-01T04:33:45Z
dc.date.available2021-10-01T04:33:45Z
dc.date.issued2021-09-15
dc.identifier.doi10.25904/1912/4357
dc.identifier.urihttp://hdl.handle.net/10072/408504
dc.description.abstractHuman papillomavirus (HPV) and its oncogenes (E6 and E7) are responsible for 5% of the entire burden of cancer and more than 99% of all cervical cancer cases. Although protection against infection was made possible with the introduction of vaccines, several challenges related to their rollout, subtype coverage, and their lack of therapeutical potential mean that little will change for several decades. Accordingly, the currently available armamentarium for the treatment of cervical cancer has not led to improvement in the therapeutic outcomes since the 1970s. In this context, the discovery of the clustered regularly interspaced short palindromic repeats (CRISPR) and the advancements in our understanding of the molecular mechanisms in the carcinogenic process have kept the doors wide open for developing potent and selective treatments for these cancers. In this thesis, we developed and utilised a messenger RNA (mRNA) modality of the highly specific AsCPF1 nuclease and optimised its topical delivery for the treatment of cervical cancer using PEGylated lipoplex-entrapped alginate scaffold (PLAS) platform. In addition, we described a potent molecular-based combination therapy for systemic administration to inhibit Aurora Kinase A (AURKA) and Phosphatidylinositol 3-kinase (PI3K) using Alisertib and Alpelisib, respectively, and we showed the sensitivity of cervical cancer to this synergistic combination. Overall, this research demonstrates the viability of improving the therapeutic outcomes for HPV-driven cancers in general and cervical cancers if careful consideration of the driving molecular mechanisms was undertaken. We showed the feasibility of safely delivering CRISPR systems using PEGylated lipoplex-entrapped alginate scaffold for the topical targeting of cervical cancer, providing new insights into the translation of CRISPR into humans, and we developed a potent molecular-based combination therapy for improving the outcomes of the treatment.en_US
dc.languageEnglish
dc.language.isoen
dc.publisherGriffith University
dc.publisher.placeBrisbane
dc.subject.keywordsHuman papillomavirusen_US
dc.subject.keywordsHPVen_US
dc.subject.keywordsCervical canceren_US
dc.subject.keywordsTreatmenten_US
dc.titleDevelopment of Novel Therapies for Human Papilloma Virus Driven Cancersen_US
dc.typeGriffith thesisen_US
gro.facultyGriffith Healthen_US
gro.rights.copyrightThe author owns the copyright in this thesis, unless stated otherwise.
gro.hasfulltextFull Text
dc.contributor.otheradvisorIdris, Adi
dc.contributor.otheradvisorParekh, Harendra
gro.identifier.gurtID000000024173en_US
gro.thesis.degreelevelThesis (PhD Doctorate)en_US
gro.thesis.degreeprogramDoctor of Philosophy (PhD)en_US
gro.departmentSchool of Pharmacy & Med Scien_US
gro.griffith.authorTayyar, Yaman A


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