Additional Relevant Details The paper entitled "Translation efficiency of mRNAs is increased by antisense oligonucleotides targeting upstream open reading frames" (Liang et al., Nature Biotechnology, Advanced Online Publication, July 2016), documents the validation of a new mechanism of action in antisense drug technology that increases the expression and production of specific therapeutic target proteins.
The findings published in Nature Biotechnology report data from a series of studies designed to increase the production of therapeutic target proteins in vivo and in vitro by increasing the translational efficiency of specific messenger RNAs (mRNA) with antisense oligonucleotides (ASO). Using their expertise in RNA technology, Ionis scientists evaluated five ASOs that bind to mRNA sequences in upstream open reading frames (uORF) within the 5' untranslated region to specifically increase the amount of protein translated from a downstream primary open reading frame (ORF). In both human and murine cells, the ASOs acting through this new mechanism of action were able to increase the amount of proteins expressed from 30% to 150% in a dose-dependent manner. In addition, the ASO-mediated increases in protein expression were sequence specific and occurred at the level of translation. These findings support the utility of these modified ASOs as a significantly useful class of therapeutic agents with broad utility.