Discovering and Calibrating Design Rules for Programming Adeno-Associated Virus Nanoparticles

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dc.contributor.advisorSuh, Junghaeen_US
dc.contributor.committeeMemberSilberg, Jonathan Jen_US
dc.contributor.committeeMemberTabor, Jeffrey Jen_US
dc.creatorHo, Michelle Lianeen_US
dc.date.accessioned2016-01-22T17:33:26Zen_US
dc.date.available2016-01-22T17:33:26Zen_US
dc.date.created2015-12en_US
dc.date.issued2015-12-03en_US
dc.date.submittedDecember 2015en_US
dc.date.updated2016-01-22T17:33:26Zen_US
dc.description.abstractEffective gene therapy must deliver therapeutic genes to disease sites while avoiding healthy tissue. However, engineering targeted gene delivery vectors to ensure exclusive delivery to diseased sites remains a challenge. Adeno-associated virus (AAV) is receiving increasing attention for its potential as a gene delivery vehicle because it offers several advantages: it is considered the safest viral vector, it infects human cells efficiently, and it can be genetically altered to improve therapeutic efficacy. However, even slight modifications to the virus capsid (the outer protein shell covering its genome) lead to unpredictable outcomes. Thus, a governing set of design rules for virus capsid assembly and function is needed to improve future engineering efforts. To this end, this thesis uncovers some of these rules by applying a computational model, often used in protein engineering, to the AAV capsid. A new strategy to improve AAV targeting was also explored by engineering AAVs to sense and become activated by extracellular proteases found in diseased tissues. The specificity of these protease-activatable viruses can be tuned to recognize a variety of protease profiles to treat a multitude of diseases. Design rules for these platform technologies are unveiled through their development and in-depth characterization. We also explore new motifs in the AAV capsid to further our understanding of AAV basic biology. Ultimately, these studies advance our ability to program virus nanoparticles for many biomedical applications.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationHo, Michelle Liane. "Discovering and Calibrating Design Rules for Programming Adeno-Associated Virus Nanoparticles." (2015) Diss., Rice University. <a href="https://hdl.handle.net/1911/88078">https://hdl.handle.net/1911/88078</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/88078en_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.subjectprotein engineeringen_US
dc.subjectgene therapyen_US
dc.subjectprotease activationen_US
dc.subjectSCHEMAen_US
dc.subjectS/T motifen_US
dc.titleDiscovering and Calibrating Design Rules for Programming Adeno-Associated Virus Nanoparticlesen_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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