Typologie d'actualités: Team Chemistry, Imaging and Exobiology

Evaluation of synthetic mRNA with selected UTR sequences and alternative Poly(A) tail, in vitro and in vivo

Messenger RNA (mRNA) has emerged as an attractive new technology of drugs. The efficacy of mRNA technology depends on both the efficiency of mRNA delivery and translation. Untranslated regions (UTRs) and the poly(A) tail play a crucial role in regulating mRNA intracellular kinetics. Intending to improve the therapeutic potential of synthetic mRNA, CBM researchers evaluated various UTRs and tail designs, using Pfizer-BioNTech COVID-19 vaccine sequences as a reference. First, they screened six 5’ UTRs (capdependent/independent), evaluated nine 5’ UTR-3’ UTR combinations, and a novel heterologous A/G tail in cell models, and in vivo using luciferase as a reporter gene.

Then, to decipher the translation mechanism of selected UTRs, they correlated mRNA expression with ribosome load, mRNA half-life, mRNA immunogenicity, and UTR structures. Results showed that the heterologous tail they introduced is as potent as the Pfizer-BioNTech tail and confirmed the high potency of the human α-globin 5’ UTR.

They also revealed the potential of the VP6 and SOD 3’ UTRs. Researchers validated their results using mRNA encoding the SARS-CoV-2 spike protein formulated as lipid nanoparticles (LNPs) for mouse immunization. Overall, the selected 3’ UTRs and heterologous A/G tail have great potential as new elements for therapeutic mRNA design.

These results open up new prospects for mRNA therapies. While improvements are still needed to achieve higher expression than existing strategies, this strategy contributes to improving mRNA therapies.

These results are linked to a patent

Reference:
Evaluation of synthetic mRNA with selected UTR sequences and alternative Poly(A)  tail, in vitro and in vivo. Medjmedj A, Genon H, Hezili D, Ngalle Loth A, Clemençon R , Guimpied C, Mollet L, Bigot A, Wien F, Hamacek J, Chapat C, Perche F, Molecular Therapy Nucleic Acids 2025.

The CBM publishes its videos on Canal U

The CBM has received support from the French National Research Agency (ANR) for the production of scientific mediation media as part of a SAPS CSTI project. We have opted for motion design videos to explain our research work to a wide audience.

The latest video, “Medical imaging: chemistry as a tool for visualizing the body's interior”, concerns research by the “Metal complexes and MRI” team into the development of new, more specific and biocompatible contrast agents.

The videos can be viewed here

 

A CBM team has developed a contrast agent capable of revealing oxidative stress in living tissue

The "Metal Complexes and MRI" team, in collaboration with a Hungarian team, has developed a contrast agent based on an iron compound associated with a fluorinated ligand. This makes it possible to map oxidative stress in living tissue, a marker of numerous pathologies. This molecular detector, still at the pre-clinical stage, could considerably enrich tomorrow's medical imaging toolkit.

This major advance has been published in the journal JACS.
Relaxation-Based In Vivo Discrimination of Oxidized and Reduced States of a Redox-Switchable 19F MRI Probe
Garda Z., Szeremeta F., Tóth C.S., Bunda S., Pifferi C., Clémençon R., Même S., Tircso G., Tóth É.
J. Am. Chem. Soc. 2025, 147, 21, 18017-18024

Find out more on the CNRS Chimie website.

 

Martina Sanadar, PhD in Environmental and Energy Engineering, is a post-doctoral fellow at CBM

Originally from Italy, Martina Sanadar has a PhD in environmental and energy engineering. She has been a post-doctoral fellow in the "Metal Complexes and MRI" team for the past year. Her research focuses on the development of bioinspired MRI contrast agents sensitive to Cu²⁺. In vivo imaging of extracellular Cu²⁺ is of great interest due to its biological importance in physiological and pathological states. However, the development of effective and selective MRI contrast agents for Cu²⁺, especially compared to the more abundant Zn²⁺ ions, remains a considerable challenge.

Martina Sanadar contributes her expertise in coordination and physical chemistry, solution thermodynamics and various techniques (potentiometry, relaxivity measurements, luminescence spectroscopy, UV-visible spectroscopy and calorimetry).

She joined the CBM for the excellence of its research, its collaborative environment and advanced equipment, as well as the opportunity to work in France. The CBM's interdisciplinary approach and international collaborations align perfectly with her professional goals, making it an ideal destination to further her career.