mRNA vaccines offer a host of complementary advantages to more traditional vaccine modalities such as DNA, protein/peptide, inactivated, and/or attenuated vaccines. These advantages include the speed of production, the ability to express complex antigens in their physiologically relevant state(s), high potency, minimal risk of genomic integration, and the absence of vector-based immunity [1]. Given these characteristics, mRNA vaccines have played a central role in controlling the SARS-CoV-2 pandemic 2, 3; their expanded use throughout diverse populations has helped establish clinical safety and efficacy at an unprecedented rate yet has concurrently highlighted some critical challenges. These clinical observations have spurred a massive expansion of research efforts, which stand to impact a myriad of diseases ranging from infection to cancer and autoimmunity 4, 5, 6.

Accordingly, herein we discuss the growing field of mucosal mRNA vaccines. Currently approved mRNA vaccines are administered via systemic injection(s). However, there is emerging interest in the designing of mRNA vaccines that are administered at mucosal sites [7]. Given this, we have attempted to summarize recent work on mucosal mRNA vaccination and in so doing share our perspectives on both opportunities and challenges within this critical area.