Manufacturing an RNA Therapeutic for Duchenne Muscular Dystrophy; Housing and Health Inequity in America: A Multi-level Analysis of the U.S. Housing System’s Resistance to Reform

Author: ORCID icon
Laudermilch, Emma, School of Engineering and Applied Science, University of Virginia
Anderson, Eric, EN-Chem Engr Dept, University of Virginia
Neeley, Kathryn, EN-Engineering and Society, University of Virginia

At just three years old, doctors diagnosed Jack Hogan with Duchenne muscular dystrophy (DMD), a genetic disorder characterized by progressive muscle degeneration and weakness. By age 7, Jack was wheelchair bound and struggled to hold his head up on his own. Because DMD has no known cure and current therapies can only treat its symptoms, Jack’s cardiovascular system was severely compromised by age 12 and at age 14, Jack sadly passed away in his home just outside Boston, Massachusetts.

In South Bronx, New York, 15-year-old Ilyna Hernandez struggles to breathe as she does her homework. She was diagnosed with asthma at a young age and now she goes about her day-to-day life feeling like somebody is sitting on her chest, restricting the airflow to her lungs. Her respiratory issues didn’t happen by chance—her neighborhood is encircled by busy highways that contribute to the above average air pollution over South Bronx. The lack of clean air is preventing Ilyna from getting better and living a normal life.

Through my senior thesis work, I aimed to address the health problems faced by Jack Hogan and Ilyna Hernandez. My technical work focused on designing a process to produce an RNA therapeutic that attacks DMD at its genetic root. This technology can extend the lives of kids like Jack so they can experience their childhoods outside of a doctor’s office. My STS research examined the relationship between housing discrimination and the health of Black Americans. By understanding the causes of health inequity, this research informs future efforts to create long-lasting reform and help Ilyna and other kids in her neighborhood to breathe.

For our capstone project, my team designed a process to manufacture golodirsen, an RNA therapeutic for the treatment of DMD. In the upstream portion of the process, golodirsen is synthesized in an in vitro reactor by feeding a sequence-optimized reaction mixture as well as additional enzymes, cap analogs, cofactors, polyamines, redox reagents, and salts to the reactor. The golodirsen solution exiting the reactor then goes through a series of downstream steps including tangential flow filtration, affinity chromatography, size exclusion chromatography, and sterile filtration to purify the product to FDA standards. To determine whether our design was financially feasible, we performed an economic analysis based on direct costs, fixed costs, and general expenses. From this analysis, we were able to price our therapeutic at $26,000 a year, 90% less than the competitor’s price of $300,000, and still achieve a substantial return on investment.

In my STS research, I studied housing discrimination and its impact on the health of Black Americans. The COVID-19 pandemic shed light on racial health disparities in the U.S. and I aimed to determine the root cause of this inequity. Using Frank W. Geels’ multi-level perspective, I analyzed the stability of the U.S. housing system in an effort to understand why residential segregation persists despite its negative impact on the health of Black communities. Through this research, I came to recognize present housing discrimination as a clear and intentional outcome of racist redlining policies from the 1930s. In the past century, residential segregation has been preserved by implicit bias among white homeowners, physical infrastructure, and lack of community investment. In the terms of the multi-level perspective
framework, these factors have acted as stabilizing forces preventing a sociotechnical transition into a fair and equitable housing system.

On the surface, the connection between my STS research and capstone project is unclear. However, it was by examining my technical problem using sociotechnical systems thinking that I began to study the accessibility of health care in the U.S. and health inequity, the topic of my STS research. The knowledge I gained through this research guided my capstone design work by placing an emphasis on affordability and heavily influenced my future engineering practice. Completing these two projects simultaneously gave me a practical understanding of engineering as social experimentation as I developed a design that would theoretically impact thousands of people. While treating engineering as experimentation traditionally emphasizes product safety, my research on health inequity led me to consider the product’s accessibility to maximize its positive impact. As engineers, we have an incredible influence on the world around us. Because of this, it is crucial that engineering students understand the technical aspects of their field as well the social implications of their work. For the next generation of engineers to truly serve the greater good, they must learn the importance of promoting equity through their work.

I would like to acknowledge my capstone team: Catherine Barton, Will McDevitt, and Daniel Torrico for all of the time and effort they put into our project this year. I would also like to thank my capstone advisor, Professor Anderson and STS research advisor, Professor Neeley for their guidance at each step of the way.

BS (Bachelor of Science)

School of Engineering and Applied Science
Bachelor of Science in Chemical Engineering
Technical Advisor: Eric Anderson
STS Advisor: Kathryn Neeley
Technical Team Members: Catherine Barton, Will McDevitt, Daniel Torrico

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