Developing a toolkit for modular adeno-associated virus surface display of peptides and proteins
| dc.contributor.advisor | Suh, Junghae | |
| dc.creator | Thadani, Nikki Nisha | |
| dc.date.accessioned | 2019-05-17T18:37:32Z | |
| dc.date.available | 2019-11-01T05:01:19Z | |
| dc.date.created | 2019-05 | |
| dc.date.issued | 2019-04-16 | |
| dc.date.submitted | May 2019 | |
| dc.date.updated | 2019-05-17T18:37:32Z | |
| dc.description.abstract | Engineering biocomputation in nanotherapeutics is a growing field for the creation of devices that respond to their environment to diagnose diseases or deliver targeted treatments. Viruses are genetically encoded nanoplatforms that come prepackaged with sense-response behaviors allowing them to navigate cellular entry, genome delivery and replication. The field of synthetic virology seeks to enhance viral performance for delivery applications by refactoring viruses into well-characterized domains that can be exchanged or augmented with exogenous functional motifs. Adeno-associated virus (AAV) is a strong candidate for modification through synthetic virology — this vector is relatively well-characterized and has a wide range of potential applications in safe and efficient gene therapy. We sought to develop modular, standardized platforms for the integration of exogenous proteins into the AAV capsid so that biological ‘parts’ identified in other systems can be translated to enhance AAV-based therapies. By applying protein engineering techniques to study and modify AAV’s innate biocomputation, we have developed a series of components that can alter the viral response to external stimulus and expand this platform’s capacity for protein and peptide outputs in addition to gene therapy. To address the challenge of genetically modifying the multifunctional virus capsid while preserving viral assembly and transduction, we have identified computational models that may be able to predict vector formation and function from the modified capsid sequence. These models can potentially accelerate the design process for engineered viral nanoparticles through in silico screening to remove non-functional variants. This toolkit will facilitate the incorporation of a wide range of proteins in AAV, expanding the vector’s capacity for detecting stimuli and responding with a range of diagnostic and therapeutic outputs. | |
| dc.embargo.terms | 2019-11-01 | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.citation | Thadani, Nikki Nisha. "Developing a toolkit for modular adeno-associated virus surface display of peptides and proteins." (2019) Diss., Rice University. <a href="https://hdl.handle.net/1911/105938">https://hdl.handle.net/1911/105938</a>. | |
| dc.identifier.uri | https://hdl.handle.net/1911/105938 | |
| dc.language.iso | eng | |
| dc.rights | Copyright 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.subject | adeno-associated virus | |
| dc.subject | AAV | |
| dc.subject | protein engineering | |
| dc.subject | nanotherapeutics | |
| dc.subject | gene delivery | |
| dc.title | Developing a toolkit for modular adeno-associated virus surface display of peptides and proteins | |
| dc.type | Thesis | |
| dc.type.material | Text | |
| thesis.degree.department | Bioengineering | |
| thesis.degree.discipline | Engineering | |
| thesis.degree.grantor | Rice University | |
| thesis.degree.level | Doctoral | |
| thesis.degree.name | Doctor of Philosophy |
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