Development of a Tethered mRNA Amplifier to increase protein expression

Abstract

Herein, we present a novel method to specifically increase a messenger RNA's (mRNA) expression at the post-transcriptional level. This is accomplished using what we term a “Tethered mRNA Amplifier.” The Tethered mRNA Amplifier specifically binds an mRNA's 3′ untranslated region and enhances its stability/translation, often doubling protein output. We test this approach on several transcripts associated with haploinsufficiency disorders and increase their steady-state expression in cell culture. We suggest this approach may be a tenable therapeutic modality with precise activity and broad-spectrum application.