Development of a Tethered mRNA Amplifier to increase protein expression

Biotechnol J. 2022 Oct;17(10):e2200214. doi: 10.1002/biot.202200214. Epub 2022 Jul 11.


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.

Keywords: gene expression; haploinsufficiency; mRNA metabolism; mRNA therapeutics; mRNA translation.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Protein Biosynthesis*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism


  • 3' Untranslated Regions
  • RNA, Messenger