Abstract
mRNA vaccines have emerged as a revolutionary tool to generate rapid and precise immune responses against infectious diseases and cancers. Compared with conventional vaccines such as inactivated viruses, viral vectors, protein subunits or DNA-based vaccines, mRNA vaccines stand out owing to multiple advantages, including simplicity of design, fast production, enhanced safety and high efficacy. Nevertheless, efficient and targeted delivery of mRNA molecules remains a significant challenge owing to their inherent instability and susceptibility to degradation. Nanotechnology offers innovative solutions to surmount these obstacles and amplify the potency of mRNA vaccines. This Primer aims to outline a modular approach to developing biomaterials and nanotechnology for mRNA vaccines, with a focus on particle design, formulation evaluation and therapeutic applications. We delve into the underlying mechanisms of nanoparticle-facilitated mRNA protection, cellular uptake, endosomal escape and immune stimulation. We underscore the critical parameters that impact the manufacturing and clinical implementation of nanomaterial-based mRNA vaccines. Finally, we present the current limitations and future perspectives in the advancement of nanotechnology-enhanced mRNA vaccines for broad applications in prophylactic and therapeutic interventions.