Encryption of Adeno-Associated Virus for Protease-Controlled Gene Therapy

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dc.contributor.advisorSuh, Junghaeen_US
dc.contributor.committeeMemberSilberg, Jonathan J.en_US
dc.contributor.committeeMemberSegatori, Lauraen_US
dc.creatorJudd, Justinen_US
dc.date.accessioned2013-09-16T15:15:45Zen_US
dc.date.accessioned2013-09-16T15:15:48Zen_US
dc.date.available2013-09-16T15:15:45Zen_US
dc.date.available2013-09-16T15:15:48Zen_US
dc.date.created2013-05en_US
dc.date.issued2013-09-16en_US
dc.date.submittedMay 2013en_US
dc.date.updated2013-09-16T15:15:48Zen_US
dc.description.abstractGene therapy holds the unprecedented potential to treat disease by manipulating the underlying genetic blueprints of phenotypic behavior. Targeting of gene delivery is essential to achieve specificity for the intended tissue, which is especially critical in cancer gene therapy to avoid destruction of healthy tissue. Adeno-associated virus (AAV) is considered the safest viral vector and, compared to non-viral vectors, offers several advantages: higher efficiency, genetic modification, combinatorial panning, and high monodispersity. Classic viral targeting has focused on engineering ligand-receptor interactions, but many cell surface targets do not support post-binding transduction events. Furthermore, many potential target tissues – such as triple negative breast cancer – may not display a single, unique identifying surface receptor, so new methods of targeting are needed. Alternatively, many pathological states, including most cancers, exhibit upregulation of proteolytic enzymes in the extracellular milieu. The present work describes the development of an AAV platform that has been engineered to activate in response to disease-related proteases. The specificity and sensitivity of these protease-activatable viruses (PAVs) can be tuned to meet the demands of various clinical scenarios, giving the platform some therapeutic versatility. This work represents the first demonstration of a protease-controlled, non-enveloped virus for genetic therapy. These results extend the therapeutic value of AAV, the safest gene vector currently being explored in 73 clinical trials worldwide.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationJudd, Justin. "Encryption of Adeno-Associated Virus for Protease-Controlled Gene Therapy." (2013) Diss., Rice University. <a href="https://hdl.handle.net/1911/71971">https://hdl.handle.net/1911/71971</a>.en_US
dc.identifier.slug123456789/ETD-2013-05-570en_US
dc.identifier.urihttps://hdl.handle.net/1911/71971en_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.subjectDirected evolutionen_US
dc.subjectAAVen_US
dc.subjectVirologyen_US
dc.subjectProteaseen_US
dc.subjectCanceren_US
dc.subjectNanoen_US
dc.titleEncryption of Adeno-Associated Virus for Protease-Controlled 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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