Abstract
Ideal gene therapy vectors would be delivered intravenously to transfect only specific cells. Existing vectors only transfect cells in vivo in a manner determined by blood flow and the site of introduction. As a general and systematic approach for generating Cell–targeting ligands for gene therapy vectors, we have used peptide–presenting phage libraries to select peptides that bind and enter several different Cell types. Because of their small size, cell–binding peptides such as these could be incorporated into biological or physical gene therapy vectors. In addition, peptide–presenting phage themselves may also be candidates for gene therapy vectors.
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References
Mulligan, R.C. The basic science of gene therapy. Science 260, 926–932 (1993).
Feigner, P.L. & Rhodes, G. Gene therapeutics. Nature 349, 351–352 (1991).
Pietersz, G.A. & McKenzie, I.F.C. Antibody conjugates for the treatment of cancer. Immunol. Rev. 129, 57–80 (1992).
Devlin, J.J., Panganiban, L.C. & Devlin, P.E. Random peptide libraries: a source of specific protein binding molecules. Science 249, 404–406 (1990).
Cwirla, S.E., Peters, E.A., Barrett, R.W. & Dower, W.J. Peptides on phage: A vast library of peptides for identifying ligands. Proc. Natl. Acad. Sci. USA 87, 6378–6382 (1990).
Hart, S.L. et al. cell binding and internalization by filamentous phage displaying a cyclic Arg-Gly-Asp-containing peptide. J. Biol. Chem. 269, 12468–12474 (1994).
Doorbar, J. & Winter, G. Isolation of a peptide antagonist to the thrombin receptor using phage display. J. Mol. Biol, 244, 361–369 (1994).
Gotten, M. et al. Transferrin-polycation-mediated introduction of DNA into human leukemic cells: Stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptors. Proc. Natl. Acad. Sci. USA 87, 4033–4037 (1990).
Brown, K.C., Yang, S-H., & Kodadek, T. Highly specific oxidative cross-linking of proteins mediated by a nickel-peptide complex. Biochem. 34, 4733–4739 (1995).
Quantin, B., Perricaudet, L.D., Tajbakhsh, S. & Mandel, J.L. Adenovirus as an expression vector in muscle cells in vivo. Proc. Natl. Acad. Sci. USA 89, 2581–2584 (1992).
Rosenfeld, M.A. et al. Adenovirus-mediated transfer of a recombinant al-antitrypsin gene to the lung epithelium in vivo. Science 252, 431–434 (1991).
Fong, S., Doyle, L.V., Devlin, J.J. & Doyle, M.V. Scanning whole cells with phage-display libraries: Identification of peptide ligands that modulate cell function. Drug Dev. Res. 33, 64–70 (1994).
Hart, S.L. et al. Gene delivery and expression mediated by an integrin-binding peptide. Gene Ther. 2, 552–554 (1995).
Yokoyama-Kobayashi, M. & Kato, S. Recombinant fl phage particles can trans-feet monkey COS-7 cells by DEAE dextran method. Biochem. Biophys. Res. Commun. 192, 935–939 (1993).
Gottschalk, S., Tweten, R.K., Smith, L.C. & Woo, S.L.C. Efficient gene delivery and expression in mammalian cells using DNA coupled with perfringolysin O. Gene Ther. 2, 498–503 (1995).
Markland, W., Roberts, B.L., Saxena, M.J., Guterman, S.K. & Ladner, R.C., Design, construction and function of a multicopy display vector using fusions to the major coat protein of bacteriophage M13. Gene 109, 13–19 (1991).
Jespers, L.S. et al. Surface expression and ligand-based selection of cDNAs fused to filamentous phage gene VI. Bio/Technology 13, 378–382 (1995).
Bassel-Duby, R., Hernandez, M.D., Gonzalez, M.A., Krueger, J.K. & Williams, R.S. A 40-kilodalton protein binds specifically to an upstream sequence element essential for muscle-specific transcription of the human myoglobin promoter. Mol. Cell. Biol. 12, 5024–5032 (1992).
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Barry, M., Dower, W. & Johnston, S. Toward cell–targeting gene therapy vectors: Selection of cell–binding peptides from random peptide–presenting phage libraries. Nat Med 2, 299–305 (1996). https://doi.org/10.1038/nm0396-299
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DOI: https://doi.org/10.1038/nm0396-299
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