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Gewählte Publikation:

Jost, PJ; Harbottle, RP; Knight, A; Miller, AD; Coutelle, C; Schneider, H.
A novel peptide, THALWHT, for the targeting of human airway epithelia.
FEBS Lett. 2001; 489(2-3):263-269 Doi: 10.1016/s0014-5793(00)02236-5 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Jost Philipp

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Targeting gene vectors to 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 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 THALWHT-displaying phages bound much stronger than phages displaying control peptides to human airway epithelial cells. In contrast, no significant binding differences were observed on a variety of non-airway-derived human cell lines suggesting selective binding of the THALWHT motif to airway epithelia. Confocal microscopy of such cells after exposure to labelled synthetic THALWHT peptide indicated that its binding is followed by specific internalisation via endocytosis. A synthetic peptide comprising a cyclic CTHALWHTC domain and a DNA binding moiety enabled efficient targeted gene delivery into human airway epithelial cells. Competition assays with free THALWHT peptide 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.
Find related publications in this database (using NLM MeSH Indexing)
Amino Acid Sequence -
Binding, Competitive -
Bronchi - cytology
Bronchi - metabolism
Caco-2 Cells -
Cell Line -
DNA - genetics
DNA - metabolism
Epithelial Cells - metabolism
Gene Transfer Techniques -
Genetic Vectors - genetics
Genetic Vectors - metabolism
HeLa Cells -
Humans -
Luciferases - genetics
Luciferases - metabolism
Microscopy, Confocal -
Oligopeptides - genetics
Oligopeptides - metabolism
Protein Binding -
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Transfection -
Tumor Cells, Cultured -

Find related publications in this database (Keywords)
phage display
airway epithelium
gene delivery
cystic fibrosis gene therapy
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