Graduation Year


Document Type

Master's Thesis


Master of Science


Biological Science

Program Director

Meredith Protas, PhD

First Reader

Vikas Bhat, PhD

Second Reader

Tyler A. Johnson, PhD


Gene therapy emerged in the late 20th century as a new frontier for drug-developers seeking to cure, rather than treat, patients with genetic diseases. Indeed, by directly addressing genetic disease at its source, gene-therapy offers a promising solution for many patients. Excitingly, after nearly half a century working to bring this promise to fruition, the scientific community has seen the approval of the first three FDA-approved gene therapies within the last two years. Though each clinical success offers hope to more patients, the realization of gene therapy from concept to clinic is a lengthy process, requiring much iteration. Consequently, overcoming the emerging issues brought to light in current clinical trials will be necessary to broaden the scope of gene therapy in curing human disease. A primary focus remains the optimization of gene delivery through the rational design of viral vectors. This optimization rests on our increasing knowledge of viral vector structure-function, which is the motivation behind the present study. Here multiple biophysical tools are used to qualitatively and quantitatively assess purified green fluorescent protein (GFP)-based virus-like particles (VLPs). Specifically, structure and stability of enveloped and non-enveloped VLPs is investigated with the focus of gaining insight into the genome-uncoating process. In two separate investigations, enveloped VLP stability as a function of pH and salt is explored, and, notably, a role of the encapsulated genome size is identified in the genome-uncoating process of non-enveloped VLPs.

Available for download on Wednesday, May 31, 2023