Advancing Precision and Controllable Molecular Tools for Genetic Engineering and Disease Treatment

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dc.contributor.advisorGao, Xueen_US
dc.contributor.advisorVerduzco, Rafaelen_US
dc.creatorZeng, Hongzhien_US
dc.date.accessioned2024-05-22T16:17:57Zen_US
dc.date.created2024-05en_US
dc.date.issued2024-04-17en_US
dc.date.submittedMay 2024en_US
dc.date.updated2024-05-22T16:17:57Zen_US
dc.descriptionEMBARGO NOTE: This item is embargoed until 2026-05-01en_US
dc.description.abstractThe emergence of programmable gene editing tools has transformed life sciences by empowering researchers to execute precise and targeted genomic alterations in living cells. The advent of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (CRISPR-Cas) technology has greatly accelerated genome editing research and applications. However, CRISPR-Cas faces limitations due to the low efficiency of homology-directed repair after Cas nuclease- induced double-stranded DNA breaks (DSBs), which can result in unintended genomic alterations and raise safety concerns. Base editors (BEs), leveraging a catalytically impaired nuclease and a single-stranded DNA deaminase enzyme, offer a promising alternative by facilitating targeted point mutations without requiring DSBs or donor DNA templates. However, the challenge of off-target effects and the lack of temporal control over BE activity when delivered via viral vectors remain significant hurdles. My thesis describes two projects that I lead: (1) A split and inducible adenine base editor for precise in vivo base editing, and (2) Precision A3G base editors and prime editors for cystic fibrosis modeling and correction. These projects explore the underlying principles of BEs, detailing engineering strategies for achieving small-molecule-controlled base editing in vivo and outline efforts to enhance the specificity of adenine and cytosine base editors. Additionally, these projects involve viral and non-viral delivery methods for BEs, emphasizing their applications in human disease modeling, treatment, and prevention. Lastly, my projects contain applications of prime editing technology, a more versatile gene-editing tool than BE, highlighting its promise for biological research and therapeutic applications.en_US
dc.embargo.lift2026-05-01en_US
dc.embargo.terms2026-05-01en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.citationZeng, Hongzhi. Advancing Precision and Controllable Molecular Tools for Genetic Engineering and Disease Treatment. (2024). PhD diss., Rice University. https://hdl.handle.net/1911/116193en_US
dc.identifier.urihttps://hdl.handle.net/1911/116193en_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.subjectCRISPRen_US
dc.subjectBase Editingen_US
dc.subjectGene Therapyen_US
dc.subjectProtein Engineeringen_US
dc.subjectGenetic Engineeringen_US
dc.titleAdvancing Precision and Controllable Molecular Tools for Genetic Engineering and Disease Treatmenten_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentChemical and Biomolecular Engineeringen_US
thesis.degree.disciplineEngineeringen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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