Molecular analyses of CRISPR-directed gene editing on the NRF2 gene
| Author(s) | Banas, Kelly Helena | |
| Date Accessioned | 2021-11-04T12:18:01Z | |
| Date Available | 2021-11-04T12:18:01Z | |
| Publication Date | 2021 | |
| SWORD Update | 2021-08-09T22:11:57Z | |
| Abstract | Lung cancer remains the leading cause of cancer-related death worldwide. As a result, the prognosis of patients diagnosed with Non-small cell lung carcinoma (NSCLC), particularly, is dismal indicating the need for continued improvement in prevention, diagnosis, and treatment. Despite this, treatment options and regimens are similar to what was originally established many years ago. Recent studies point to the evolution of drug resistance in lung cancer as being centered, in part, on the upregulation of various genes involved in controlling efflux or drug inactivation. Among these genes is Nuclear Factor Erythroid 2-related Factor 2 (NRF2), which is considered a master regulator of 100-200 target genes involved in cellular responses to oxidative and/or electrophilic stress. There is a subset of NSCLC patients who carry mutations in NRF2, which cause the transcription factor to act like an oncogene, favoring cell survival and growth in cancerous cells; these mutations also create new recognition sites for cleavage and gene disruption by CRISPR/Cas9, making NRF2 a good molecular target. While the oncogenic role of NRF2 continues to be investigated, there is a gap in knowledge of the molecular mechanism involved during and after CRISPR-directed knockout of NRF2 in solid tumor cells. To address this, I proposed establishing a clinically relevant model system to study the site-specific efficacy and fidelity of CRISPR/Cas9 for targeting NRF2. With this approach, I identified the global gene expression profile after CRISPR-directed gene disruption which helps to establish the structure-function relationship of CRISPR-induced mutations in NRF2. These data begin to define the molecular framework upon which safe and efficacious therapeutic strategies can be built. | en_US |
| Advisor | Kmiec, Eric B. | |
| Degree | Ph.D. | |
| Department | University of Delaware, Department of Medical and Molecular Sciences | |
| DOI | https://doi.org/10.58088/3js9-8856 | |
| Unique Identifier | 1282610152 | |
| URL | https://udspace.udel.edu/handle/19716/29342 | |
| Language | en | |
| Publisher | University of Delaware | en_US |
| URI | https://login.udel.idm.oclc.org/login?url=https://www.proquest.com/dissertations-theses/molecular-analyses-crispr-directed-gene-editing/docview/2572622943/se-2 | |
| Keywords | NRF2 | en_US |
| Keywords | CRISPR | en_US |
| Keywords | Gene editing | en_US |
| Title | Molecular analyses of CRISPR-directed gene editing on the NRF2 gene | en_US |
| Type | Thesis | en_US |