Engineering Linear Cap-independent mRNA Vaccines with Intrinsic 1 Adjuvanticity for Potent Cancer Immunotherapy

We present 25 a streamlined linear cap-independent RNA (LciRNA) cancer vaccine platform that achieves stable 26 expression in vivo without 5’ capping or ribonucleotide modification, and innately stimulates 27 immune responses to enhance antitumor immunity. By fusing a UPA protective sequence, composed 28 of a viral exoribonuclease-resistant RNA (xrRNA) and a poly(A) binding protein (PABP) motif, 29 with an optimized Enterovirus A internal ribosome entry site, LciRNA resists 5’ exonuclease decay 30 and drives superior in vivo expression.