Enhancing mRNA stability through untranslated region engineering for therapeutic application

Abstract

mRNAs are widely studied for therapeutic applications. However, the instability of mRNAs and the lack of their translation efficiency are still challenges for the development of mRNA therapeutics. The translation efficiencies of mRNAs are largely dependent on the stability of mRNAs. The stability of an mRNA is a function of the sequence of nucleotides and secondary structures. Particularly, 5’- and 3’-untranslated regions are well known as the regulatory elements of mRNA stability. In this study, I used two strategies to enhance the stability of mRNAs. The first one is to find the novel stable motifs by long-read sequencing. Through long-read sequencing, the mRNA stability can be revealed at the transcript isoform level. I find some of the stabilizing elements by comparing the different stabilities of transcript isoforms. The second strategy is by analyzing the mechanism of the known stable UTR sequences with respect to the RNA binding proteins. Identifying the RNA stabilizing proteins, the diversity of UTR design can be further increased.