Evaluation of synthetic mRNA with selected UTR sequences and alternative poly(A) tail, in vitro and in vivo
Ayoub Medjmedj, Hugo Genon, Dounia Hezili, Albert Ngalle Loth, Rudy Clémençon, Cyril Guimpied, Lucile Mollet, Anne Bigot, Frank Wien, Josef Hamáček, Clément Chapat, Federico Perche
Abstract
using luciferase as a reporter gene. Then, to decipher the translation mechanism of selected UTRs, we correlated mRNA expression with ribosome load, mRNA half-life, mRNA immunogenicity, and UTR structures. Our results showed that the heterologous tail we introduced is as potent as the Pfizer-BioNTech tail and confirmed the high potency of the human α-globin 5' UTR. They also revealed the potential of the VP6 and SOD 3' UTRs. We validated our results using mRNA encoding the SARS-CoV-2 spike protein formulated as lipid nanoparticles (LNPs) for mouse immunization. Overall, the selected 3' UTRs and heterologous A/G tail have great potential as new elements for therapeutic mRNA design.