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Mapping alveolar binding sites in vivo using phage peptide libraries

Gene Therapy volume 10, pages 1429–1436 (2003)Cite this article

Abstract

Targeting lung tissue is nonselective due in part to the lack of specific cell-surface receptors identified on target lung cells. We used in vivo phage display to identify a panel of peptides that can bind selectively to lung epithelial cells with less binding to nonepithelial cells. By direct intratracheal instillation of phage libraries into the lung, we isolated and identified 143 individual phage clones. Three phage clones revealed enhanced binding to the lung in vitro and in vivo. These three identified peptides were synthesized and demonstrated selective binding to epithelial cells in lung tissue versus the control peptide. Further, the peptides specifically bound to freshly isolated type II alveolar epithelial cells compared with Hep2 cells. The results suggest that the airway phage display approach could be exploited for analyzing the molecular diversity in the lower respiratory tract.

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Acknowledgements

We are grateful to Dr G Smith of the University of Missouri for the phage peptide libraries. We thank M Brown, T Evanoff, JR Wagner, M Goheen, and Z Zhu for technical help. This work was supported by National Institutes of Health Grants NCI PO1-CA75426, RO1 AI48455, and R21 HL72363.

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Authors and Affiliations

  1. Department of Medicine, Indiana University School of Medicine, Indianapolis, 46202, IN, USA

    M Wu & P A Smith

  2. College of Medicine, University of Cincinnati Medical Center, PO Box 670555, Cincinnati, 45267, OH, USA

    R Pasula & W J Martin II

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  1. M Wu
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  2. R Pasula
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  3. P A Smith
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  4. W J Martin II
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Wu, M., Pasula, R., Smith, P. et al. Mapping alveolar binding sites in vivo using phage peptide libraries. Gene Ther 10, 1429–1436 (2003). https://doi.org/10.1038/sj.gt.3302009

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