Elucidating the effects of nucleic acid aptamers on protein aggregation
- Author(s): Tran, Claire
- Advisor(s): Chen, Irene A
- et al.
Protein aggregation is an important topic for human health and biotechnology, with consequences in areas ranging from neurodegenerative diseases to therapeutic protein production yields. With these concerns in mind, methods to modulate protein aggregation are therefore essential. One suggested method to reduce protein aggregation is the use of nucleic acid aptamers, i.e., single-stranded nucleic acids that have been selected to specifically bind to a target. Previous studies in some systems have demonstrated that aptamer binding to their protein target inhibit aggregation. However, the mechanisms by which aptamers might reduce aggregation have not been fully determined. In the studies described here, we investigated published aptamers that target a-synuclein and Green Fluorescent Protein (GFP) and their influence on protein aggregation. A kinetic and structural analyses were performed to assess the mechanistic effect of the selected aptamers on protein aggregation. An observation in each study indicated the presence of aptamers resulted in an increase of higher order intermediates (i.e., oligomers) in solution. The increase in oligomer population due to aptamers highlights a potential mechanism by which aptamers may modulate the aggregation properties of proteins. The modulatory effect of aptamers on protein aggregation can significantly impact biotechnology by proposing alternative methods to address disease and protein therapeutics.