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

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dc.contributor.advisorSuh, Junghae
dc.creatorEvans, Annicka Carter
dc.date.accessioned2019-05-16T18:08:24Z
dc.date.available2019-05-16T18:08:24Z
dc.date.created2019-05
dc.date.issued2018-12-10
dc.date.submittedMay 2019
dc.date.updated2019-05-16T18:08:24Z
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.
dc.format.mimetypeapplication/pdf
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>.
dc.identifier.urihttps://hdl.handle.net/1911/105351
dc.language.isoeng
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.
dc.subjectadeno-associated virus
dc.subjectAAV
dc.subjectgene therapy
dc.subjectbiocomputing nanoparticles
dc.subjectstimulus-responsive
dc.subjecttargeted therapeutics
dc.subjectprotease-responsive
dc.subjectprotease
dc.subjectoxidative stress
dc.subjectNrf2
dc.subjectKeap1
dc.subjectn-terminal externalization
dc.titleDeveloping stimulus-responsive adeno-associated virus vectors for cancer-targeted gene therapy
dc.typeThesis
dc.type.materialText
thesis.degree.departmentBioengineering
thesis.degree.disciplineEngineering
thesis.degree.grantorRice University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy
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