The development of lipid-based mRNA delivery systems has significantly advanced mRNA therapeutics. Liposomes, particularly histidylated liposomes (LYX), have demonstrated their efficacy in delivering nucleic acids. In this study, LYX liposomes were optimized by adding a freeze-drying and extrusion steps, resulting in improved size distribution and storage stability. LYX liposomes maintained their size (150 ± 10 nm) and polydispersity index (0.10 ± 0.02) for up to one year at 4°C, while preserving their transfection efficacy. They exhibited high mRNA encapsulation rate (∼95%) and protected it from RNase degradation. The lamellar organization was confirmed by Small Angle X-ray Scattering and CryoTEM. These liposomes allow efficient transfection of both cell lines and primary cells, albeit with lower efficacy compared to commercial vectors, due to slower cell uptake and reduced endosomal escape. They have demonstrated the ability to deliver mRNA encoding therapeutic BMP2 and BMP9 molecules, leading to the production of functional proteins capable of activating BMP signaling pathway. Additionally, in vivo studies confirmed their potential for mRNA delivery, when incorporated into hydrogels and implanted subcutaneously in mice. These findings highlight LYX liposomes as a promising and versatile platform for mRNA delivery in therapeutic applications.

This work involved laboratories from two Institutes: the Centre de Biophysique Moléculaire (CNRS Chimie) and the Laboratoire de Biologie, Bioingénierie et Bioimagerie Ostéo-Articulaires (CNRS Ingénierie).

Reference :
Albert Ngalle Loth, Manon Maroquenne, Ayoub Medjmedj, Franck Coste, Thomas Bizien, Chantal Pichon, Delphine Logeart-Avramoglou, Federico Perche.
Structural and functional characterization of a histidylated liposome for mRNA deliveryStructural and functional characterization of a histidylated liposome for mRNA delivery.
Journal of Controlled Release (2025) Volume 379, pages 164-176, doi: 10.1016/j.jconrel.2025.01.010.