The misfolding or clumping of proteins, known as aggregation, is one of the leading causes of neurogenerative diseases such as Alzheimer’s, Huntington’s, and Parkinson’s diseases. It has recently been demonstrated that nucleic acids can act as strong molecular chaperones, assisting in protein folding and prevention of aggregation in vitro. This project strived to detect nucleic acid chaperone activity in vivo in Escherichia coli through the use of a fluorescent protein biomarker, mNeptune. E. coli strains were prepared with two vectors, one for an individual RNA G-quadruplex sequence previously shown to have potent chaperone activity and one with mNeptune. The cells were co-expressed, and the fluorescence was measured using a plate reader and flow cytometry. Higher fluorescence indicated a more successfully folded protein and thus, higher chaperone activity. The chaperone nucleic acid activity was compared to the activity of traditional protein-protein chaperones such as GroEl and DNAK. A quantifiable, consistent increase in fluorescence due to chaperone nucleic acid activity was not identified. This lack of significant activity is likely due to the negative charge on mNeptune at physiological pH, preventing potent interaction with the negatively charged RNA. Moreover, this assay could work effectively with other fluorescent protein variants.