Developing stimulus-responsive adeno-associated virus vectors for cancer-targeted gene therapy

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dc.contributor.advisorSuh, Junghaeen_US
dc.creatorEvans, Annicka Carteren_US
dc.date.accessioned2019-05-16T18:08:24Zen_US
dc.date.available2019-05-16T18:08:24Zen_US
dc.date.created2019-05en_US
dc.date.issued2018-12-10en_US
dc.date.submittedMay 2019en_US
dc.date.updated2019-05-16T18:08:24Zen_US
dc.description.abstractThe most significant challenge to current gene therapy trials is ensuring delivery to exclusively diseased sites. Both non-viral and viral vectors have broad natural tropisms that elicit off-target side effects when used as a treatment. Adeno-associated virus (AAV) has recently become the most commonly used vector for gene therapy trials because it offers many advantages: it has low pathogenicity in humans, infects most cell types with great efficiency, and can be genetically altered to improve its therapeutic effect. The rapid advancement of viral engineering techniques combined with these innate abilities of AAV serotypes to transduce cells, opens up the possibility for creating recombinant AAV platforms that can act as particles with targeting capabilities. It has therefore been the focus of my research to both understand the innate stimulus-responsive nature of AAV as well as work to develop a cancer-targeted AAV vector through capsid engineering. The designed cancer-targeting platforms utilize known characteristics of the tumor microenvironment and cancer biology - specifically the upregulation of matrix-metalloproteinases and production of reactive oxygen species. The characterization of these stimulus-responsive designs, in combination with the investigation of wild-type n-terminal extrusion in response to temperature and pH, will greatly enhance our understanding of AAV engineering tolerance, and further expand the targeting strategies for the use of this vector for human gene therapy.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationEvans, Annicka Carter. "Developing stimulus-responsive adeno-associated virus vectors for cancer-targeted gene therapy." (2018) Diss., Rice University. <a href="https://hdl.handle.net/1911/105351">https://hdl.handle.net/1911/105351</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/105351en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectadeno-associated virusen_US
dc.subjectAAVen_US
dc.subjectgene therapyen_US
dc.subjectbiocomputing nanoparticlesen_US
dc.subjectstimulus-responsiveen_US
dc.subjecttargeted therapeuticsen_US
dc.subjectprotease-responsiveen_US
dc.subjectproteaseen_US
dc.subjectoxidative stressen_US
dc.subjectNrf2en_US
dc.subjectKeap1en_US
dc.subjectn-terminal externalizationen_US
dc.titleDeveloping stimulus-responsive adeno-associated virus vectors for cancer-targeted gene therapyen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentBioengineeringen_US
thesis.degree.disciplineEngineeringen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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