Fiche publication
Date publication
février 2003
Journal
Proceedings of the National Academy of Sciences of the United States of America
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BECHINGER Burkhard
,
Dr KICHLER Antoine
Tous les auteurs :
Kichler A, Leborgne C, März J, Danos O, Bechinger B
Lien Pubmed
Résumé
Gene delivery has shown potential in a wide variety of applications, including basic research, therapies for genetic and acquired diseases, and vaccination. Most available nonviral systems have serious drawbacks such as the inability to control and scale the production process in a reproducible manner. Here, we demonstrate a biotechnologically feasible approach for gene delivery, using synthetic cationic amphipathic peptides containing a variable number of histidine residues. Gene transfer to different cell lines in vitro was achieved with an efficiency comparable to commercially available reagents. We provide evidence that the transfection efficiency depends on the number and positioning of histidine residues in the peptide as well as on the pH at which the in-plane to transmembrane transition takes place. Endosomal acidification is also required. Interestingly, even when complexed to DNA these peptides maintain a high level of antibacterial activity, opening the possibility of treating the genetic defect and the bacterial infections associated with cystic fibrosis with a single compound. Thus, this family of peptides represents a new class of agents that may have broad utility for gene transfer and gene therapy applications.
Mots clés
Amino Acid Sequence, Animals, Anti-Bacterial Agents, administration & dosage, Cell Line, DNA, administration & dosage, Endosomes, metabolism, Histidine, chemistry, Humans, Hydrogen-Ion Concentration, Mice, Molecular Sequence Data, Peptides, Rabbits, Transfection
Référence
Proc. Natl. Acad. Sci. U.S.A.. 2003 Feb;100(4):1564-8
