Chemically synthesized, non-capped and non-polyadenylated peptide-coding RNA efficiently induces antigen-specific CD8+ T cells
ChemRNAs are chemically synthesized RNA lacking typical mRNA features that are nevertheless efficiently translated by CD8+ T cells to overcome limitations associated with in vitro transcription for developing anti-cancer
Recombinant in vitro-transcribed mRNA is widely used for vaccination and has been evaluated in numerous clinical studies for multiple indications. However, traditional mRNA features such as the 5' cap, 5' untranslated region, start and stop codons, 3' untranslated region, and 3' poly(A) tail are typically included to enhance translation efficiency. Contrary to current dogma, researchers have demonstrated that short, chemically synthesized RNA oligonucleotides lacking some or all of these features can be efficiently translated when they encode epitopes recognized by CD8+ T cells. One design, termed ChemRNA with the structure 5'-OH-AUG-coding sequence-3'-OH, strongly stimulates antigen-specific CD8+ T cells both in vitro and in vivo. This finding challenges the current understanding of canonical mRNA structure and introduces the possibility that defective or supposedly non-coding RNA may encode human and murine major histocompatibility complex class I-associated peptides. The results also suggest that ChemRNA could help overcome challenges associated with the design and purification of individualized anti-cancer vaccines. The use of chemically synthesized, non-capped, and non-polyadenylated peptide-coding RNA offers a promising approach for developing novel mRNA-based therapies.