Targeted gene delivery into alpha9beta1-integrin-displaying cells by a synthetic peptide.
We have investigated the usefulness of two small synthetic peptides comprising either a linear or a cyclic PLAEIDGIEL domain and a DNA-binding moiety of 16 lysine residues to mediate gene transfer selectively into alpha9beta1-integrin-displaying cells. Such specific gene delivery could only be achieved with the peptide containing the cyclic PLAEIDGIEL domain. However, inclusion of the cationic liposome Lipofect-AMINE into the peptide/DNA complexes resulted for both peptides in efficient gene transfer with significant targeting specificity. Naturally, the integrin alpha9beta1 is present only in a few highly specialised tissues and abundant throughout the human airway epithelia in vivo. Targeting gene vectors to this integrin therefore appears a useful approach to gene therapy of lung diseases such as cystic fibrosis. As the integrin alpha9beta1 is associated with tissue differentiation during foetal development and may cause resurgence of the foetal phenotype in colon cancers, such vectors may also be applicable for prenatal and cancer gene therapy.
Schneider
H
H
Division of Biomedical Sciences, Imperial College School of Medicine, London, UK. h.schneider@ic.ac.uk
Harbottle
R P
RP
Yokosaki
Y
Y
Jost
P
P
Coutelle
C
C
D002411:Cation Exchange Resins; D002448:Cell Adhesion / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics; D005353:Fibronectins / Q000235:genetics; D018390:Gene Targeting; D017930:Genes, Reporter; D006801:Humans; D016023:Integrins / Q000235:genetics*; D008055:Lipids; D008081:Liposomes; D010446:Peptide Fragments / Q000235:genetics*; D019063:Tenascin / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D002411:Cation Exchange Resins; D004268:DNA-Binding Proteins; D005353:Fibronectins; D016023:Integrins; D008055:Lipids; C086724:Lipofectamine; D008081:Liposomes; D010446:Peptide Fragments; D019063:Tenascin; C113256:integrin alpha 9 beta 1