A novel peptide, THALWHT, for the targeting of human airway epithelia
Identifieur interne : 002288 ( Main/Exploration ); précédent : 002287; suivant : 002289A novel peptide, THALWHT, for the targeting of human airway epithelia
Auteurs : P. J. Jost [Royaume-Uni, Allemagne] ; R. P. Harbottle [Royaume-Uni] ; A. Knight [Royaume-Uni] ; A. D. Miller [Royaume-Uni] ; C. Coutelle [Royaume-Uni] ; H. Schneider [Royaume-Uni, Allemagne]Source :
- FEBS Letters [ 0014-5793 ] ; 2001.
English descriptors
- Teeft :
- Airway, Airway epithelial cells, Assay, Average result, Binding moiety, Biopanning, Black bars, Caco2, Cell surface, Control phage, Control phages, Coutelle, Cthalwhtc, Cyaan, Epithelial, Epithelium, Error bars, Feb, Free cthalwhtc, Further incubation, Geel, Geel zwart, Geel zwart jost, Gene, Gene delivery, Gene transfer, Ggcthalwhtc, Harbottle, Human airway epithelia, Human airway epithelial cells, Jost, Life technologies, Ligand, Luciferase, Luciferase activity, Moiety, Peptide, Peptide cthalwhtc, Phage, Receptor, Retardation units, Same experiment, Standard deviations, Such cells, Synthetic peptide, Synthetic peptides, Target cells, Thalwht, Thalwht motif, Thalwht peptide, Third round, Viral vectors, White bars, Zwart.
Abstract
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.
Url:
DOI: 10.1016/S0014-5793(00)02236-5
Affiliations:
- Allemagne, Royaume-Uni
- Angleterre, Bavière, District de Moyenne-Franconie, Grand Londres
- Erlangen, Londres
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Le document en format XML
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Knight</name><affiliation wicri:level="3"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Cystic Fibrosis Gene Therapy Research Group, Section of Molecular Genetics, Division of Biomedical Sciences, Imperial College School of Medicine, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Miller, A D" sort="Miller, A D" uniqKey="Miller A" first="A. D." last="Miller">A. D. 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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.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Bavière</li><li>District de Moyenne-Franconie</li><li>Grand Londres</li></region><settlement><li>Erlangen</li><li>Londres</li></settlement></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Jost, P J" sort="Jost, P J" uniqKey="Jost P" first="P. J." last="Jost">P. J. Jost</name></region><name sortKey="Coutelle, C" sort="Coutelle, C" uniqKey="Coutelle C" first="C." last="Coutelle">C. Coutelle</name><name sortKey="Harbottle, R P" sort="Harbottle, R P" uniqKey="Harbottle R" first="R. P." last="Harbottle">R. P. Harbottle</name><name sortKey="Knight, A" sort="Knight, A" uniqKey="Knight A" first="A." last="Knight">A. Knight</name><name sortKey="Miller, A D" sort="Miller, A D" uniqKey="Miller A" first="A. D." last="Miller">A. D. Miller</name><name sortKey="Schneider, H" sort="Schneider, H" uniqKey="Schneider H" first="H." last="Schneider">H. Schneider</name></country><country name="Allemagne"><region name="Bavière"><name sortKey="Jost, P J" sort="Jost, P J" uniqKey="Jost P" first="P. J." last="Jost">P. J. Jost</name></region><name sortKey="Schneider, H" sort="Schneider, H" uniqKey="Schneider H" first="H." last="Schneider">H. Schneider</name><name sortKey="Schneider, H" sort="Schneider, H" uniqKey="Schneider H" first="H." last="Schneider">H. Schneider</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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