Synthesis of novel ionisable lipids for designing liponanoparticles for mRNA delivery

University of Brest
3 to 6 months
35 hours per week

The recent SARS-CoV-2 pandemic has accelerated significant scientific advances in mRNA technology, including mRNA-based vaccines and other mRNA-based therapies (gene editing, prime editing), which have now become commonplace. Furthermore, mRNA has emerged as an innovative therapeutic platform for personalised medicine. However, the efficient delivery of mRNA therapeutics requires further development of delivery systems that can protect and transport mRNA to specific target cells. Lipid nanoparticles (LNPs) are currently the most advanced strategy in this area, but optimising them to improve encapsulation, biocompatibility and intracellular release remains a major challenge.

LNP constructions typically comprise four components: an ionizable lipid, a phospholipid, cholesterol and a PEG lipid. Of these, the ionizable lipid, which is the most extensively studied, is the key focus for developing new formulations. Until now, ionizable lipids have mainly been produced using commercially available, this significantly limits structural diversity.

We hypothesised that integrating novel functionalities into ionizable lipids by developing original structures could enhance their efficacy and selectivity with respect to specific organs. This internship is part of a research project that aims to design and develop new families of ionizable lipids that could broaden mRNA formulations and enhance their efficacy, biodistribution and tolerability.

Location : Faculté des Sciences et Techniques, Laboratoire CEMCA UMR CNRS6521 /Laboratory CEMCA, UMR CNRS 6521, Team Chimie Organique Santé Matériaux (COSM), groupe Phosphore et Lipides

Internship allowance : 600 euros per month as per national law

Tasks and duties entrusted to the student:

The intern will be expected to:

  • Carry out the organic synthesis of novel ionizable lipid molecules
  • Characterize the compounds using classical analytical techniques (NMR, mass spectrometry, chromatography)
  • Participate in the preliminary evaluation of their formulation as delivery systems
  • Present the project's results and progress during team meetings

The applicant should:

  • be enrolled in the final year of a Master's degree in Chemistry, specialising in organic, medicinal or biomolecular chemistry.
  • Have solid practical and theoretical knowledge in organic synthesis and structural analysis
  • Demonstrate a strong interest in interdisciplinary research (chemistry-biology interface). Show scientific rigour, independence and good organisational skills.
Dr Mathieu BERCHEL (MCF-HDR) phone : +33 0298016286 mathieu.berchel@univ-brest.fr