2025 AIChE Annual Meeting

(182h) Enhancing mRNA Stability of RBD Protein for Improved COVID-19 Vaccine Development

Authors

Qing Sun, Texas A&M University
The success of messenger RNA (mRNA)-based COVID-19 vaccines has highlighted their transformative potential in addressing viral pandemics. However, limitations in mRNA stability and efficient protein expression remain significant barriers to improving vaccine storage, distribution, and overall effectiveness. This highlights the need to develop mRNA vaccines with more stability and overall effectiveness. This study investigates strategies to enhance the stability and translational efficiency of mRNA sequences encoding the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein.

Codon optimization and increased secondary structure are linked to mRNA stability. Using our in-house machine learning algorithm, we found mRNA sequences with optimized codon usage and secondary structure. Stability assays in solution revealed improved mRNA longevity compared to unoptimized and other alternative sequences. Additionally, the optimized sequences exhibited higher protein expression levels in cell-based systems.

These findings underscore the potential for mRNA sequence engineering to generate more stable and translationally efficient mRNA vaccine candidates. Our work offers valuable insights for the development of next-generation mRNA vaccines with improved stability, increased expression efficiency, and greater overall effectiveness.