title: Design and evaluation of histidine-rich amphipathic peptides for siRNA delivery.
abstract: 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.
authors.affiliation: Genethon, 1bis rue de l'Internationale, BP60, 91002 Evry, France.
authors.forename: Bérangère
authors.initials: B
authors.lastname: Langlet-Bertin
authors.forename: Christian
authors.initials: C
authors.lastname: Leborgne
authors.forename: Daniel
authors.initials: D
authors.lastname: Scherman
authors.forename: Burkhard
authors.initials: B
authors.lastname: Bechinger
authors.forename: A James
authors.initials: AJ
authors.lastname: Mason
authors.forename: Antoine
authors.initials: A
authors.lastname: Kichler
mesh_terms: 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
chemical_list: D010455:Peptides; D034741:RNA, Small Interfering; D006639:Histidine
references.citation: Mol Ther. 2009 Jan;17(1):95-103
references.pmid: 18957965
references.citation: Bioconjug Chem. 2008 Jul;19(7):1448-55
references.pmid: 18553894
references.citation: Biochim Biophys Acta. 2006 Mar;1758(3):301-7
references.pmid: 16540079
references.citation: J Gene Med. 2001 Mar-Apr;3(2):135-44
references.pmid: 11318112
references.citation: Nucleic Acids Res. 2003 Jun 1;31(11):2717-24
references.pmid: 12771197
references.citation: Chembiochem. 2008 Nov 24;9(17):2787-9
references.pmid: 18972467
references.citation: J Gene Med. 2005 Jul;7(7):977-86
references.pmid: 15772938
references.citation: J Biol Chem. 1991 Sep 15;266(26):17707-12
references.pmid: 1832676
references.citation: Nature. 2001 May 24;411(6836):494-8
references.pmid: 11373684
references.citation: J Biol Chem. 2003 Nov 7;278(45):44826-31
references.pmid: 12944394
references.citation: Br J Pharmacol. 2009 May;157(2):166-78
references.pmid: 19459843
references.citation: Cancer Gene Ther. 2005 Oct;12(10):787-95
references.pmid: 15891770
references.citation: Mol Ther. 2002 Feb;5(2):104-14
references.pmid: 11829517
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16050-5
references.pmid: 17913877
references.citation: Biochim Biophys Acta. 2009 Apr;1790(4):219-30
references.pmid: 19714863
references.citation: Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7297-301
references.pmid: 7638184
references.citation: Med Sci Monit. 2006 Apr;12(4):RA67-74
references.pmid: 16572063
references.citation: Biochemistry. 2007 Apr 24;46(16):4785-92
references.pmid: 17391006
references.citation: Bioconjug Chem. 2006 Sep-Oct;17(5):1209-18
references.pmid: 16984130
references.citation: Nat Rev Genet. 2007 Mar;8(3):173-84
references.pmid: 17304245
references.citation: J Control Release. 2008 Aug 25;130(1):57-63
references.pmid: 18599144
references.citation: J Mol Med (Berl). 2007 Feb;85(2):191-201
references.pmid: 17111132
references.citation: J Control Release. 2007 Aug 16;121(1-2):64-73
references.pmid: 17588702
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1564-8
references.pmid: 12563034
references.citation: J Gene Med. 2005 Nov;7(11):1459-67
references.pmid: 16041686
references.citation: Proc Natl Acad Sci U S A. 1988 Nov;85(21):7972-6
references.pmid: 2973058
references.citation: FASEB J. 2006 Feb;20(2):320-2
references.pmid: 16352649
references.citation: Bioconjug Chem. 1999 May-Jun;10(3):406-11
references.pmid: 10346871
references.citation: Annu Rev Med. 2005;56:401-23
references.pmid: 15660519
references.citation: Gene Ther. 2006 Sep;13(18):1313-9
references.pmid: 16953249
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9742-7
references.pmid: 11481446
references.citation: J Mol Med (Berl). 2005 Oct;83(10):764-73
references.pmid: 16028076
references.citation: Biochemistry. 2007 Oct 9;46(40):11253-62
references.pmid: 17848098