Trinucleotide Cap Analogue Bearing a Locked Nucleic Acid Moiety: Synthesis, mRNA Modification, and Translation for Therapeutic Applications

Abstract

The synthesis of a new trinucleotide cap analogue containing a locked nucleic acid (LNA) moiety such as m^7(LNA)G(5')ppp(5')A_mpG and its molecular biology applications are described. The most appealing feature is that this new cap analogue outperforms the standard trinucleotide cap m⁷G(5')ppp(5')A_mpG and the anti-reverse cap analogue m₂^{7,3'-<i>O</i>}G(5')ppp(5')G by a factor of 5 in terms of translational efficiency.