title: Characterization of the gene transfer process mediated by histidine-rich peptides.
abstract: Peptides have an interesting potential as gene transfer agents not only because they are biodegradable but also due to their reduced size and the facility of product characterization and large-scale production. Recently, we have shown that the cationic amphipathic 26-mer peptide LAH4 possesses high DNA delivery capacities. To better understand its way of functioning and to further improve its efficiency, we synthesized and tested various LAH4 derivatives. The evaluation of their DNA delivery capacity, as well as their transfection efficiency, makes accessible valuable information about structure-function correlations. In particular, our results indicate the threshold peptide concentration for endosomal escape and conformational preferences for the peptide. Furthermore, the results indicate that a fine balance of peptide-DNA interactions is responsible for the high transfection activity of LAH4. Taken together, the data also suggest that the peptides efficiently transport DNA into the cytoplasm and that the creation of more potent transfection compounds probably needs improvement of other steps during the process.
authors.affiliation: Généthon-CNRS UMR 8115, 1bis rue de l'Internationale, BP60, 91002 Evry, France. akich@genethon.fr
authors.forename: Antoine
authors.initials: A
authors.lastname: Kichler
authors.forename: Christian
authors.initials: C
authors.lastname: Leborgne
authors.forename: Olivier
authors.initials: O
authors.lastname: Danos
authors.forename: Burkhard
authors.initials: B
authors.lastname: Bechinger
mesh_terms: D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000493:pharmacokinetics; D018014:Gene Transfer Techniques; D006639:Histidine; D006801:Humans; D008968:Molecular Conformation; D010455:Peptides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides; D006639:Histidine; D004247:DNA