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

Jost PJ, Harbottle RP, Knight A, Miller AD, Coutelle C, Schneider H (2001)

Publication Type: Journal article, Original article

Publication year: 2001

Journal

Febs Letters Elsevier

Book Volume: 489

Pages Range: 263-269

Journal Issue: 2-3

DOI: 10.1016/S0014-5793(00)02236-5

Abstract

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. © 2001 Federation of European Biochemical Societies.

Authors with CRIS profile

Holm Schneider

Involved external institutions

Imperial College London / The Imperial College of Science, Technology and Medicine GB United Kingdom (GB) Technische Universität München (TUM) DE Germany (DE)

How to cite

APA:

Jost, P.J., Harbottle, R.P., Knight, A., Miller, A.D., Coutelle, C., & Schneider, H. (2001). A novel peptide, THALWHT, for the targeting of human airway epithelia. Febs Letters, 489(2-3), 263-269. https://doi.org/10.1016/S0014-5793(00)02236-5

MLA:

Jost, Philipp J., et al. "A novel peptide, THALWHT, for the targeting of human airway epithelia." Febs Letters 489.2-3 (2001): 263-269.

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