Researcher ORCID Identifier

https://orcid.org/0000-0002-1803-7261

Graduation Year

2021

Date of Submission

11-2029

Document Type

Campus Only Senior Thesis

Degree Name

Bachelor of Arts

Department

Neuroscience

Reader 1

Katherine Smith

Reader 2

Gretchen Edwalds-Gilbert

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Terms of Use for work posted in Scholarship@Claremont.

Rights Information

© 2020 Grace K Pratt

Abstract

Glioblastoma (GBM) is the most aggressive and invasive type of malignant primary brain tumors in humans. Classified as a grade IV glioma, the prognosis of those diagnosed with GBM has not improved significantly over the last few decades, with the median survival of patients ranging from 15-20 months. One major obstacle in GBM treatment is the blood-brain barrier (BBB), which protects the central nervous system (CNS) from substances that could cause damage through restriction of passive transport as well as enzymatic and immunologic barriers. The BBB prevents the majority of chemotherapy drugs from reaching functional brain tissue and mutations in many GBMs are also resistant to therapeutics. The discovery of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems provides new potential for gene therapies via CRISPR-based therapeutics. Here, I review the known genetic landscape of GBMs, highlighting the most common mutations and potential therapeutic targets, as well as current methods of delivery of CRISPR/Cas systems to the CNS. I then propose a future study to test the potential of graphene oxide mediated CRISPR delivery for GBM treatment through targeted knockdown of known proto-oncogene EGFR and EGFRvIII, mutant, as previous studies have shown that graphene oxide is both an effective method of CRISPR delivery in vitro and drug delivery in vivo. Determining the efficacy of graphene oxide CRISPR delivery across the BBB could provide new methods of delivery of gene therapy for treatment of neurological diseases, including GBM.

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