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Genetic research

Novel Artificial 5'UTR Increases Modified mRNA Translation Efficiency in Cardiac Tissue

Strategic Insights

— 2 min read

Investigators at Icahn School of Medicine at Mount Sinai have made significant breakthroughs in cancer gene therapy by designing a novel artificial 5' untranslated region (5'UTR) that enhances modified mRNA translation efficiency in cardiac tissue. According to the research, the artificial 5'UTR, termed "Top Heart 5'UTR," significantly improves translation efficiency in cardiomyocytes (CMs) and heart cells both in vitro and in vivo. This innovative design may contribute to the development of a superior modRNA platform for use in preclinical and clinical studies, potentially allowing reduced dosages or increased gene expression at the same dosage level.

Key Takeaways:

  • The novel artificial 5'UTR, "Top Heart 5'UTR," was designed based on ribonucleotide frequency analyses of 1000 genes highly expressed in the heart, containing a unique 20-nucleotide sequence that consists of 11 previously uncharacterized nucleotides and 9 well-described nucleotides from the Kozak sequence upstream of the start codon.
  • The design significantly improves modRNA translation efficiency in cardiomyocytes (CMs) and heart cells both in vitro and in vivo, with a 30-60% increase in translation efficiency in both mouse and human CMs compared to a standard 5'UTR control.
  • The artificial 5'UTR induces a 2-2.5 times higher translation of modRNA in the mouse heart 24 and 48 h post-delivery.
  • The research concluded that the findings may contribute to the development of a superior modRNA platform for use in preclinical and clinical studies, potentially allowing reduced dosages or increased gene expression at the same dosage level.
  • The novel artificial 5'UTR design can be extended to identify optimized 5'UTRs for various cell types or organs, including applications in cancer therapies.
  • Ann Anu Kurian, lead author of the study, noted that "Due to the high production cost and short half-life of modRNA, it is essential to identify novel 5'UTR designs that enhance modRNA translation in the heart." (Icahn School of Medicine at Mount Sinai)

Statistics:

  • 1000 genes highly expressed in the heart were analyzed to design the novel artificial 5'UTR.
  • 20-nucleotide sequence was added to the 5'UTR design.
  • 11 previously uncharacterized nucleotides and 9 well-described nucleotides from the Kozak sequence were incorporated into the 20-nucleotide sequence.
  • The novel artificial 5'UTR design increased translation efficiency by approximately 30-60% in both mouse and human CMs compared to a standard 5'UTR control.
  • A 2-2.5 times higher translation of modRNA was induced in the mouse heart 24 and 48 h post-delivery.

Sources:

  • Kurian, A. A., et al. (2025). Novel Artificial 5'UTR Increase Modified mRNA Translation When Injected into Mouse Heart. Pharmaceutics, 17(4), 490. (Pharmaceutics - http://www.mdpi.com/journal/pharmaceutics/)
  • NewsRx. Reports Outline Cancer Gene Therapy Study Results from Icahn School of Medicine at Mount Sinai (Novel Artificial 5'UTR Increase Modified mRNA Translation When Injected into Mouse Heart). Cardiovascular Week. May 12, 2025; p 35.

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