A novel peptide, THALWHT, for the targeting of human airway epithelia

Targeting gene vectors to human airway epithelial cells may help to overcom e the current inefficiency of gene transfer as the major problem confrontin g cystic fibrosis gene therapy, To elucidate novel ligands targeting abunda nt, apically located receptors on airway epithelial cells, a phage display library was screened for peptides binding with high affinity to such cells, This screening yielded a selectively enriched amino acid sequence, Thr-His -Ala-Leu-Trp-His-Thr (THALWHT). Subsequent binding studies confirmed that T HALWHT-displaying phages bound much stronger than phages displaying control peptides to human airway epithelial cells. In contrast, no significant bin ding differences were observed on a variety of non-airway-derived human cel l lines suggesting selective binding of the THALWHT motif to airway epithel ia. Confocal microscopy of such cells after exposure to labelled synthetic THALWHT peptide indicated that its binding is followed by specific internal isation via endocytosis, A synthetic peptide comprising a cyclic CTHALWHTC domain and a DNA binding moiety enabled efficient targeted gene delivery in to human airway epithelial cells. Competition assays with free THALWHT pept ide confirmed the specificity of gene delivery. Thus, the THALWHT motif may prove a useful targeting moiety for both non-viral and viral gene therapy vectors. (C) 2001 Federation of European Biochemical Societies, Published b y Elsevier Science B.V. All rights reserved.