The article of Ali, Arsène and Perrine has just been published!
© 2026 EPFL
We are very pleased to share that our recent developments in the field of lipid nanoparticles (LNPs) for gene delivery has just been published in ACS Applied Nano Materials. This work was conducted in collaboration with the team of Prof. Jörg Huwyler at the University of Basel, who performed the biological evaluation of the novel LNP formulations engineered in our group.
In this study, Dr Alireza Kavand designed a synthetic platform to produce structurally defined PEG-alternative polymer-lipid conjugates, enabling precise control over polymer chain length and lipid tail identity. Formulated into pDNA-loaded LNPs, these derivatives achieved up to 18-fold higher transgene expression, in vitro, than formulations currently used in clinics. Mechanistic studies pointed toward enhanced endosomal escape induced by the presence of these novel polymer-lipid derivatives. In vivo investigation in zebrafish larvae (ZFL) confirmed efficient systemic circulation and superior transgene expression without apparent toxicity. Further investigation led by Dr Perrine Robin highlighted the versatility of these novel lipid components, which also demonstrated superior properties in siRNA loaded LNPs. We thank Arsène Tergalinsky who contributed the synthetic developments of the PEG-alternative polymer-lipid conjugates during his internship in our group.
Swiss National Science Foundation - Sinergia Grant N° CRSII—222794 / 1
Kuzucu, E. Ü.; Kavand, A.; Tergalinsky, A. T.; Herbster, L.; Wang, D.; Cavegn, A.; Robin, P.; Huwyler, J.; Detampel, P.; Gerber-Lemaire, S. Steric Stabilization of Lipid Nanoparticles by Sequence-Defined Polymer–Lipids Enhances Gene Expression. ACS Appl. Nano Mater. 2026. https://doi.org/10.1021/acsanm.6c04234.