BIOLOGICAL MATERIAL AND USES THEREOF

摘要

Targeted gene delivery into human airway epithelial cells may help to overcome the current inefficiency of gene transfer as the major problem confronting cystic fibrosis gene therapy. To elucidate novel ligands targeting abundant, apically located receptors on differentiated airway epithelial cells, a random peptide 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 revealed that THALWHT-displaying phages bound much stronger than phages displaying control peptides to the two human airway epithelial cell lines tested, whereas on a variety of non-airway-derived human cell lines no significant binding differences were observed, suggesting selective binding of the THALWHT-motif to airway epithelia. A synthetic peptide comprising a cyclic CTHALWHTC domain and a DNA-binding moiety of 16 lysine residue was shown to enable efficient, targeted gene delivery into human airway epithelial cell lines.