This research article, published in ACS Central Science in 2021 by Kellie D. Nance and Jordan L. Meier, explores the role of N1-methylpseudouridine (m1Ψ), a modified nucleobase, in the development and effectiveness of COVID-19 mRNA vaccines. The authors highlight the importance of m1Ψ in reducing the immunogenicity of mRNA vaccines, thereby minimizing harmful side effects. They also discuss the potential impact of m1Ψ on mRNA translation, suggesting that it may enhance protein production in some contexts. The article concludes by emphasizing the importance of continued research into RNA modifications for the development of improved mRNA therapies.