Safer practices and novel modalities for clinical CRISPR applications
Abstract/Contents
- Abstract
- CRISPR technologies have revolutionized the field of medicine and granted us the power to precisely diagnose or edit the human genome to treat disease and to elucidate the potential causes and solutions to disorders. In my thesis, I aim to tackle two main projects to help move CRISPR-based therapeutics into clinical use and many other projects that I contributed to that helped push the boundaries on current CRISPR technologies. First, I explored the potential del- eterious side effects from gene editing. I assess whether CRISPR editing can lead to the formation and display of neoantigens, or antigens that have not been previously encountered by the immune system and which may be potentially immunogenic. I found that CRISPR editing can indeed lead to neoantigen formation and I also computationally predict that this phenome- non can occur with relative frequency, underscoring the need for safer clinical gene editing practices. To help circumvent this issue and reduce the potential for neoantigen-induced host- versus-graft disease, I develop a tool, SAFE-EDIT, which can computationally predict when this phenomenon may occur and better inform guide RNA design for best therapeutic practices. Second, I explore utilizing CRISPR as an antiviral to treat influenza, SARS-CoV-2, and other coronaviruses. I use CRISPR to interfere with both host genes essential for viral replication and with the viral genome itself, finding that both can strongly reduce viral burden in cells and together lead to an increased antiviral effect. Furthermore, treatment with small-molecule in- hibitors and CRISPR antivirals shows a strong synergistic effect at reducing the viral load, highlighting that CRISPR can be used to augment existing therapies. The high efficiency, spec- ificity, and simplicity of CRISPR opens the potential for a bevy of new applications clinically. In sum, my thesis work greatly expands CRISPR as a clinically relevant tool by further deline- ating best practices for safe therapeutic use and establishing new modalities for the treatment of infectious disease.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Abbott, Timothy Robert |
|---|---|
| Degree supervisor | Qi, Lei, (Professor of bioengineering) |
| Thesis advisor | Qi, Lei, (Professor of bioengineering) |
| Thesis advisor | Bryant, Zev David |
| Thesis advisor | Li, Jin (Billy) |
| Degree committee member | Bryant, Zev David |
| Degree committee member | Li, Jin (Billy) |
| Associated with | Stanford University, Department of Bioengineering |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Timothy Robert Abbott. |
|---|---|
| Note | Submitted to the Department of Bioengineering. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/yq046dp8439 |
Access conditions
- Copyright
- © 2021 by Timothy Robert Abbott
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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