Leveraging mRNAs sequences to express SARS-CoV-2 antigens in vivo

Chunxi Zeng; Xucheng Hou; Jingyue Yan; Chengxiang Zhang; Wenqing Li; Weiyu Zhao; Shi Du; Yizhou Dong

Based on this study, several criteria should be considered in the design of mRNA UTRs: (1) . Regarding the 5' UTR, the length is critical and the optimal sequences tested in this work do not exceed 70nt. And it should be free of certain regulatory elements, e.g. TOP motifs, secondary structure, upstream open reading frame, and microRNA binding site. (2) . In terms of 3' UTR, secondary structures may benefit protein production. A plausible explanation is that such structure in 3' UTR might prevent ribosome from skipping the stop codon and reaching mRNA 3' end that triggers Non-Stop mRNA Decay (NSD) 46 . Long 3' UTR length does not necessarily provide additional translation benefits. Long 3' UTR typically contains a mixture of positive and negative cis-regulatory elements 11 . Although it is challenging to obtain a long endogenous 3' UTR with only positive elements, specific positive cis-regulatory motifs in 3' UTRs may be used to improve mRNA translation. R3U, a HuR binding motif added to 3' UTR, enhanced protein expression, consistent with the observation in their natural context 34, 35 . This indicates that certain positive cis-regulatory elements may be used as an important UTR component. author/funder. All rights reserved. No reuse allowed without permission.