Innate sensing of mRNA vaccines

Abstract

With the recent success of mRNA vaccines and the approval of several RNA oligonucleotide therapeutics, RNA holds great promise for future drug development. The rise of RNA therapeutics has been enabled by the tremendous progress in our understanding of the sophisticated cellular mechanisms that disarm potentially dangerous exogenous RNA and safeguard RNA homeostasis. Exogenous RNA, such as an mRNA vaccine when injected, faces an intricate system of immune-sensing receptors, restriction factors, and nucleases referred to as nucleic acid immunity. A careful analysis of the functional interaction between the innate response to mRNA, the efficacy to translate the encoded protein antigen, and the quality of the resulting adaptive immunity bears great potential for further improvement of mRNA vaccines and RNA therapeutics for various clinical applications. In this review, we summarize the most recent efforts to advance mRNA vaccines by capitalizing on recent insight in innate RNA sensing.