Oligonucleotide‐Linked Lipid Nanoparticles as a Versatile mRNA Nanovaccine Platform

Abstract An effective delivery platform is crucial for the development of mRNA vaccines and therapeutics. Here, a versatile platform utilizing cholesterol‐modified oligonucleotides (L‐oligo) that bind to the mRNA within lipid nanoparticles (LNP), and enables the effective delivery of the mRNA into target cells is introduced. mRNA incorporated into LNPs via linkage with L‐oligo, termed oligonucleotide‐linked LNP (lnLNP), is superior in cellular uptake and transfection efficiency in target cells in vitro and in vivo, compared to the conventional LNP formulations. It is further applied lnLNP as an mRNA vaccine platform for SARS‐CoV‐2, demonstrating robust induction of neutralizing activity as well as polyfunctional SARS‐CoV‐2‐specific T‐cell response in vivo. The current strategy can be versatilely applied to different LNP platforms, for vaccine and therapeutic applications against various diseases, such as infections and cancers.