Nonviral delivery of self-amplifying RNA vaccines

TLDR

Despite more than two decades of research and development on nucleic acid vaccines, there is still no commercial product for human use. The study aimed to develop a self‑amplifying RNA vaccine leveraging recent lipid nanoparticle delivery advances. The authors encapsulated a 9‑kb self‑amplifying RNA in lipid nanoparticles for nonviral delivery. The LNP‑encapsulated vaccine markedly increased immunogenicity, eliciting broad, potent, and protective immune responses comparable to viral delivery but without viral vector limitations, supporting further evaluation of nonviral self‑amplifying RNA vaccines.

Abstract

Despite more than two decades of research and development on nucleic acid vaccines, there is still no commercial product for human use. Taking advantage of the recent innovations in systemic delivery of short interfering RNA (siRNA) using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA. This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors. Given the many positive attributes of nucleic acid vaccines, our results suggest that a comprehensive evaluation of nonviral technologies to deliver self-amplifying RNA vaccines is warranted.