Design and evaluation of histidine-rich amphipathic peptides for siRNA delivery.
OBJECTIVE
Short linear peptides have a high potential for delivering various drugs with therapeutic potential, including nucleic acids. Recently, we have shown that the cationic amphipathic histidine-rich peptide LAH4 (KKALLALALHHLAHLALHLALALKKA) possesses high plasmid DNA delivery capacities. Since such peptides are thought to efficiently disrupt endosomal membranes, we have tested their ability to deliver small interfering RNA (siRNA) into mammalian cells.


METHODS
Using a human cell line stably transfected with a luciferase-encoding expression vector, we have evaluated the ability of LAH4 and five derivatives thereof to deliver siRNAs and silence gene expression.


RESULTS
The six peptides are all efficient siRNA delivery vehicles whose efficiency in mediating gene silencing in 911-Luc cells was greater than that of commercially available compounds including Lipofectamine, DOTAP and polyethylenimine. In addition, by using the proton pump inhibitor bafilomycin A1, we show that efficient siRNA delivery to the cytosol requires acidification of the endosomes.


CONCLUSIONS
The LAH4 histidine-rich cationic amphipathic peptides represent an interesting and promising family of compounds for siRNA delivery.
Langlet-Bertin
Bérangère
B
Genethon, 1bis rue de l'Internationale, BP60, 91002 Evry, France.
Leborgne
Christian
C
Scherman
Daniel
D
Bechinger
Burkhard
B
Mason
A James
AJ
Kichler
Antoine
A
D000595:Amino Acid Sequence; D002460:Cell Line; D016503:Drug Delivery Systems; D015195:Drug Design; D006639:Histidine / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry* / Q000235:genetics
D010455:Peptides; D034741:RNA, Small Interfering; D006639:Histidine
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