Non-viral delivery of self-amplifying RNA

Abstract

Despite two decades of research on nucleic acid vaccines, there is still no commercial product for human use. Taking advantage of the recent innovations around systemic delivery of siRNA using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that delivery of a 9 kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared to delivery of naked RNA. This novel vaccine technology was tested with genes encoding antigens from several viral pathogens and found to elicit broad and potent immune responses. Humoral and cellular immune responses were comparable to a viral delivery technology (without the inherent limitations of viral vectors) and superior to plasmid DNA (pDNA) delivered using electroporation (EP). Our results suggest that a comprehensive evaluation of non-viral technologies to deliver self-amplifying RNA vaccines is warranted