Expression of SARS-CoV-2 Spike Protein (SP) and ACE2 via Lentiviral Vectors (LVs) to Target Glioblastoma (GBM): In Vitro Model for Viral-Mediated Fusogenic Therapy and Tumor Suppression; Neglecting Care: Ethical Failures in Long-Term Monitoring and Emotional Well-Being for CRISPR-Edited Children in He Jiankui's Experiment

Author:
Lafferty, Bryn, School of Engineering and Applied Science, University of Virginia
Advisors:
Purow, Benjamin, Neurology, University of Virginia
Laugelli, Benjamin, Engineering and Society, University of Virginia
Abstract:

My technical capstone project and my STS research paper are connected through their focus on biotechnology and its ethical, medical, and regulatory implications. My capstone explores a novel fusogenic therapeutic approach using the SARS-CoV-2 spike protein to trigger cell fusion in glioblastoma (GBM) cells, aiming to reduce tumor progression and enhance immune response. Meanwhile, my STS research examines the ethical ramifications of He Jiankui’s 2018 experiment on CRISPR-Cas9 gene-edited babies through the lens of care ethics. While my technical work investigates the potential benefits of viral-based therapies in cancer treatment, my STS research highlights emerging biotechnologies' risks and ethical challenges. Both projects underscore the complex relationship between scientific innovation, societal responsibility, and ethical oversight.

My technical project focuses on how the cyclic or continuous expression of SARS-CoV-2 spike (SP) and ACE2 receptor proteins influences the immune response to GBM, an aggressive brain tumor with poor prognosis. Using lentiviral transduction, SP and ACE2 will be expressed in GBM cells to induce syncytia formation—highly immunogenic multinucleated cell structures. This project involves in vitro and in vivo modeling, utilizing a doxycycline-inducible system to regulate protein expression. In vitro experiments with U251 and CT2A GBM cell lines will evaluate syncytia formation and cytotoxic effects using fluorescence microscopy and a Nano-Glo luciferase assay. In vivo, mice implanted with doxycycline-inducible GBM cells will undergo cyclic or continuous SP/ACE2 expression to assess immune response, measured via an ELISA assay for anti-SP antibodies. This project integrates experimental and computational methods to investigate a viral protein-based therapeutic strategy that leverages COVID-19 virus dynamics to improve GBM treatment. If successful, this approach could offer a new direction for GBM treatment by leveraging viral fusion mechanisms to enhance therapeutic outcomes.

My STS research paper investigates the ethical failures surrounding He Jiankui’s gene-editing experiment, using a care ethics framework to assess the social and emotional ramifications for the genetically modified children, Lulu and Nana. While much of the discourse on this case has focused on regulatory breaches and scientific misconduct, my analysis emphasizes the lack of consideration for the children’s long-term well-being, psychological development, and social integration. By comparing Jiankui’s actions to historical cases of scientific overreach, my paper highlights the broader implications of gene editing, arguing that future biomedical innovations must prioritize relational responsibilities and the lived experiences of affected individuals.

Working on these two projects simultaneously has deepened my understanding of the intersection between biotechnology and ethics. My capstone project reinforced the importance of rigorous oversight in emerging therapies, as even well-intentioned scientific advancements can have unintended consequences. Conversely, my STS research prompted me to reflect on the long-term impact of my technical work, particularly regarding patient safety, informed consent, and ethical responsibility in biomedical engineering. This experience has strengthened my appreciation for the necessity of ethical frameworks in shaping the development and implementation of new biotechnologies. Moving forward, I intend to apply these insights to future research and product development, ensuring that scientific progress aligns with ethical integrity and societal well-being.

Degree:
BS (Bachelor of Science)
Keywords:
Glioblastoma, SARS-CoV-2 Wuhan Spike Protein, Syncytia, CRISPR Gene Editing, Ethics
Notes:

School of Engineering and Applied Science

Bachelor of Science in Biomedical Engineering

Technical Advisor: Benjamin Purow

STS Advisor: Benjamin Laugelli

Technical Team Members: Kimball Sheehan, Furman Wall, Ashley Hemp

Language:
English
Rights:
All rights reserved (no additional license for public reuse)
Issued Date:
2025/04/29