N-terminal modification of an LAH4-derived peptide increases mRNA delivery in the presence of serum.

Fiche publication

Date publication

mars 2024

Journal

Journal of peptide science : an official publication of the European Peptide Society

Auteurs

Membres identifiés du Cancéropôle Est :
Pr BECHINGER Burkhard , Pr FOURNEL Sylvie

Tous les auteurs :
Dussouillez C, Lointier M, Sebane MK, Fournel S, Bechinger B, Kichler A

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/38523558

Résumé

The recently developed mRNA-based coronavirus SARS-CoV-2 vaccines highlighted the great therapeutic potential of the mRNA technology. Although the lipid nanoparticles used for the delivery of the mRNA are very efficient, they showed, in some cases, the induction of side effects as well as the production of antibodies directed against particle components. Thus, the development of alternative delivery systems is of great interest in the pursuit of more effective mRNA treatments. In the present work, we evaluated the mRNA transfection capacities of a series of cationic histidine-rich amphipathic peptides derived from LAH4. We found that while the LAH4-A1 peptide was an efficient carrier for mRNA, its activity was highly serum sensitive. Interestingly, modification of this cell penetrating peptide at the N-terminus with two tyrosines or with salicylic acid allowed to confer serum resistance to the carrier.