Thesis Portfolio

Perumal, Krishan, School of Engineering and Applied Science, University of Virginia
Laugelli, Benjamin, Department of Engineering and Society, University of Virginia
Farber, Charles, Center for Public Health Genomics, University of Virginia

My technical work and my STS research are linked by the technology of CRISPR, which has gained prominence in the past decade for its remarkable specificity in genetic engineering and its potential to alleviate many debilitating diseases that humanity currently faces. While linked by CRISPR, my two works differ in their temporal contexts of CRISPR-based therapies. My technical work focuses on the development of a CRISPR-based therapeutic. It posits an experimental layout for initial development and testing. In contrast, my STS research focuses on the ethics and implications of the approval of CRISPR-based therapy once the development and testing periods conclude and the product is ready to be commercialized.
My technical work involved creating novel CRISPR-based therapies for diseases with inadequate current treatment modalities, specifically osteoporosis. Osteoporosis is a hereditary disease that is characterized by low bone mineral density, and the current standard of care includes temporary fixes, such as pharmaceutical drugs, or responsive action, such as surgical intervention. Genome-wide association Studies (GWAS) have found numerous single nucleotide polymorphisms (SNPs), individual nucleotide variations in the genetic code, that are correlated to osteoporosis. Despite this, no actual genetic treatment to treat osteoporosis has been developed to this date. To leverage these databases to create a potential therapeutic, I designed a prime editing construct (An iteration of CRISPR that can change a single nucleotide with high fidelity) to target one such SNP in the gene MPDZ. There is no literature associating this gene with bone homeostasis, but the individual SNP within the gene was highly linked with bone mineral density. I hoped that by using one of the SNPs identified by a GWAS in my prime editing study, I would be able to elucidate MPDZ’s role in bone homeostasis while also paving the way for developing a genetic therapeutic for osteoporosis in the future.
My STS research also explores CRISPR technology but focuses instead on its approval as a commercial drug and the ethics behind the decision. It focuses on the approval of the drug Casgevy, which was recently pushed into the public eye as the first CRISPR therapy approved by the FDA, having been used to cure people of sickle cell anemia in clinical testing, most notably, a woman named Victoria Gray. The framework of care ethics is used to examine the FDA’s approval of Caesgevy, as it has come into recent scrutiny as to its future implications for healthcare and society. My claim is that by the goals of care ethics, which include attentiveness, responsibility, competence, and responsiveness, the FDA was justified in its approval of Casgevy. My paper further explores this claim and validates it through the contexts of personalized medicine, equity and accessibility, and societal responsibility and the common good. Overall, my research aims to analyze the first case of a CRISPR-based therapy being approved for use and to justify its approval to set a precedent for future therapies.
Working on both the technical development of CRISPR therapies and the ethical scrutiny of these technologies simultaneously has provided a practical perspective that enriched my understanding of both fields. Immersing myself in the development of CRISPR therapy first and then working to reflect on the approval of one made me learn and internalize all facets of this technology while garnering new perspectives and insights about its use and perception. As I move forward into my medical career, these insights will be crucial in ensuring that the therapies I develop or advocate for are both scientifically sound and ethically grounded, making me a more educated and empathetic physician.

BS (Bachelor of Science)
CRISPR, Gene Editing
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