Article (Scientific journals)
New Basic Membrane-Destabilizing Peptides For Plasmid-Based Gene Delivery In Vitro And In Vivo
Rittner, K.; Benavente, A.; Bompard-Sorlet, A. et al.
2002In Molecular Therapy, 5 (2), p. 104-114
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Abstract :
[en] We have designed new basic amphiphilic peptides, ppTG1 and ppTG20 (20 amino acids), and evaluated their efficiencies in vitro and in vivo as single-component gene transfer vectors. ppTG1 and ppTG20 bind to nucleic acids and destabilize liposomes consisting of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and cholesterol (3:1 mol/mol) at pH 5 and pH 7. Complexes of plasmid DNA and ppTG1 gave rise to efficient transfection in a variety of human and murine cell lines at low charge ratios ([+/-] between 1 and 2). In cell culture experiments, such vectors were superior to the membrane-destabilizing peptide KALA. In comparison with cationic lipid-, dendrimer-, and polymer-based transfection agents like Superfect, polyethylenimine (PEI), and Lipofectin, ppTG1 vectors showed good transfection efficiencies, especially at low DNA doses. Moreover, we demonstrated for the first time successful gene transfer in living animals with a single-component peptide vector. In the mouse, intravenous injection of a luciferase expression plasmid complexed with ppTG1 or ppTG20 led to significant gene expression in the lung 24 hours after injection. Structure-function studies with ppTG1, ppTG20, and sequence variants suggest that the high gene transfer activity of these peptides is correlated with their propensity to exist in alpha-helical conformation, which seems to be strongly influenced by the nature of the hydrophobic amino acids.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Rittner, K.
Benavente, A.
Bompard-Sorlet, A.
Heitz, F.
Divita, G.
Brasseur, Robert ;  Université de Liège - ULiège > Gembloux Agro-Bio Tech
Jacobs, E.
Language :
English
Title :
New Basic Membrane-Destabilizing Peptides For Plasmid-Based Gene Delivery In Vitro And In Vivo
Publication date :
2002
Journal title :
Molecular Therapy
ISSN :
1525-0016
eISSN :
1525-0024
Publisher :
Nature Publishing Group, United Kingdom
Volume :
5
Issue :
2
Pages :
104-114
104-14
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 24 June 2010

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