Methods for Gene Transfer Using DNA-Adenovirus Conjugates

  • David T. Curiel
Part of the Methods in Molecular Medicine book series (MIMM, volume 7)

Abstract

Strategies have been developed to accomplish gene delivery via the receptor-mediated pathway employing molecular conjugate vectors (1-13). As cells possess endogenous pathways for internalization of macromolecules, the utilization of these pathways for the purpose of DNA delivery represents a strategy that potentially allows certain practical advantages. In this regard, these cellular internalization pathways can be highly efficient. For example, internalization of the iron transport protein transferrin can be on the order of thousands of molecules per minute per cell (14,15). These pathways thus represent a potentially efficient physiologic method to transport DNA across the cell membrane of eukaryotic cells. To accomplish gene transfer via receptor-mediated endocytosis, a vehicle must be derived that allows DNA entry into these cellular pathways. For this purpose, molecular conjugate vectors have been derived. These vector agents consist of two linked functional domains: a DNA-binding domain to transport the DNA as part of the vector complex, and a ligand domain to target a cellular receptor that allows entry of the conjugate-DNA complex into a receptor-mediated endocytosis pathway. For incorporating DNA into the complex for gene delivery, binding must be achieved in a nondamaging, reversible manner. For this linkage, an electrostatic association between the binding domain and the nucleic acid is accomplished. To achieve this, the DNA binding domain is comprised of a polycationic amine, such as poly(L)lysine. This can associate with the negatively charged DNA in an electrostatic, noncovalent manner. To achieve entry of the complex through a receptor-mediated pathway, a ligand for the target cell is utilized. The ligand domain is covalently linked to the polylysine to create the molecular conjugate vector. The ligand domain may be a native or synthetic cell surface receptor ligand, an antireceptor antibody, or other agent that allows specific association with target cell membranes.

Keywords

Surfactant Toxicity Glycerol Albumin Argon 

References

  1. 1.
    Wu, G. Y., Wilson, J M., Shalaby, F., Grossman, M., Shafritz, D A, and Wu, C. H. (1991) Receptor-mediated gene delivery in vivo Partial correction of genetic analbuminemia in nagase rats. J. Biol. Chem 266, 14,338–14,342.PubMedGoogle Scholar
  2. 2.
    Wu, G Y. and Wu, C. H (1988) Receptor-mediated gene delivery and expression in vivo.J Biol Chem 263, 14,621–14,624.PubMedGoogle Scholar
  3. 3.
    Zenke, M., Steinlein, P., Wagner, E., Cotten, M., Beug, H, and Birnstiel, M. L (1990) Receptor-mediated endocytosis of transferrin-polycation conjugates: an efficient way to introduce DNA into hematopoletic cells. Proc Natl Acad. Sci USA 87, 3655–3659.PubMedCrossRefGoogle Scholar
  4. 4.
    Zatloukal, K, Wagner, E., Cotten, M., et al. (1992) Transferrinfection: a highly efficient way to express gene constructs in eukaryotic cells Ann. NY Acad Sci 660, 136–153.PubMedCrossRefGoogle Scholar
  5. 5.
    Wagner, E., Cotten, M., Foisner, R., and Binstiel, M. L (1991) Transferrin-polycation-DNA complexes: the effect of polycations on the structure of the complex and DNA delivery to cells. Proc Natl Acad. Sci USA 88L, 4255–4259.CrossRefGoogle Scholar
  6. 6.
    Wagner, E., Zatloukal, K., Cotten, M., et al. (1992) Coupling of adenovirus to transferrin-polylysine/DNA complexes greatly enhances receptor-mediated gene delivery and expression of transfected genes. Proc Natl Acad Sci USA 89, 6099–6103.PubMedCrossRefGoogle Scholar
  7. 7.
    Wagner, E., Zenke, M., Cotten, M., Beug, H., and Birnstiel, M. L (1990) Transferrin-polycation conjugates as carriers for DNA uptake into cells Proc Natl Acad Sci. USA 87, 3410–3414.PubMedCrossRefGoogle Scholar
  8. 8.
    Cotten, M., Lange-Rouault, F., Kirlappos, H., et al. (1990) Transferrin-polycation-mediated introduction of DNA into human leukemic cells: stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels. Proc. Natl. Acad. Sci USA 87, 4033–4037.PubMedCrossRefGoogle Scholar
  9. 9.
    Curiel, D. T, Agarwal, S., Wagner, E., and Cotten, M. (1991) Adenovirus enhancement of transferrin-polylysine-mediated gene delivery, Proc. Natl. Acad. Sci USA 88, 8850–8854.PubMedCrossRefGoogle Scholar
  10. 10.
    Rosenkranz, A. A, Yachmenev, S. V, Jans, D. A., et al. (1992) Receptor-mediated endocytosis and nuclear transport of a transfecting DNA construct. Exp. Cell Res. 199, 323–329.PubMedCrossRefGoogle Scholar
  11. 11.
    Ferkol, T, Kaetzel, C. S., and Davis, P. B. (1993) Gene transfer into respiratory epithelial cells by targeting the polymeric immunoglobulin receptor. J Clin Invest. 92, 2394–2400.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Citro, G., Perrotti, D., Cucco, C., et al. (1992) Inhibition of leukemia cell proliferation by receptor-mediated uptake of cmyb antisense oligodeoxynucleotides. Proc. Natl. Acad. Sci USA 89, 7031–7035.PubMedCrossRefGoogle Scholar
  13. 13.
    Curiel, D. T., Wagner, E., Cotten, M., et al. (1992) High efficiency gene transfer mediated by adenovirus coupled to DNA-polylysine complexes. Hum. Gene Ther. 3, 147–154.PubMedCrossRefGoogle Scholar
  14. 14.
    Huebers, H. and Finch, C. (1987) The physiology of transferrin receptors. Physiol. Rev 67, 520–582.PubMedGoogle Scholar
  15. 15.
    Thortesen, K. and Romslo, I (1990) The role of transferrin in the mechanism of cellular iron uptake Biochem J 271, 1–10.Google Scholar
  16. 16.
    Cotten, M, Wagner, E., and Birnstiel, M. L. (1993) Receptor mediated transport of DNA into eukaryotic cells Methods Enzymol 217, 618–644.PubMedCrossRefGoogle Scholar
  17. 17.
    Wilson, J.M., Grossman, M, Cabrera, J A., Wu, C H.,and Wu, G Y. (1992a) A novel mechanism for achieving transgene persistence in vivo after somatic gene transfer into hepatocytes J Biol Chem 267, 11,483–11,489.PubMedGoogle Scholar
  18. 18.
    Baatz, J E, Bruno, M D., Ciraolo, P. J., Glasser, S W, Stripp, B. R., Smyth, K. L., and Korfhagen, T R. (1994) Utilization of modified surfactant-associated protein B for delivery of DNA to airway cells in culture. Proc Natl Acad Sci USA 91, 2547–2551.PubMedCrossRefGoogle Scholar
  19. 19.
    Pastan, I., Seth, P, FitzGerald, D., and Willingham, M. (1986) Adenovirus entry into cells Some new observations on an old problem, in Virus Attachment and Entry into Cells (Crowell, R. L. and Lonberg-Holm, K., eds), American Society for Microbiology, Washington, DC, pp. 141–146.Google Scholar
  20. 20.
    Kielian, M. and Jungerwirth, S (1990) Mechanisms of enveloped virus entry into cells. Mol. Biol Med. 7, 17–31.PubMedGoogle Scholar
  21. 21.
    Fernandez-Puentes, C and Carrasco, L. (1980) Viral infection permeabilizes mammalian cells to protein toxins. Cell 20, 769–775.PubMedCrossRefGoogle Scholar
  22. 22.
    FitzGerald, D. J. P., Padmanabhan, R., Pastan, I., and Willingham, M C (1983) Adenovirus-induced release of epidermal growth factor and pseudomonas toxin into the cytosol of KB cells during receptor-mediated endocytosis Cell 32, 607–617.PubMedCrossRefGoogle Scholar
  23. 23.
    Chardonnet, Y and Dales, S (1970) Early events in the interaction of adeno-viruses with HeLa cells 1. Penetration of Type 5 and intracellular release of the DNA genome. Virology 40, 462–477.PubMedCrossRefGoogle Scholar
  24. 24.
    Svensson, U. and Persson, R. (1984) Entry of adenovirus 2 into HeLa cells. J Virol 51, 687–694.PubMedCentralPubMedGoogle Scholar
  25. 25.
    Wickham, T. J., Mathias, P., Cheresh, D A., and Nemerow, G. R. (1993) Integrins avβ3 and avβ5 promote adenovirus internalization but not virus attachment. Cell 73, 309–319.PubMedCrossRefGoogle Scholar
  26. 26.
    Seth, P., FitzGerald, D., Ginsberg, H., Willingham, M., and Pastan, I. (1984) Evidence that the penton base of adenovirus is involved in potentiation of toxicity of Pseudomonas exotoxin conjugated to epidermal growth factor, Mol. Cell. Biol 4, 1528–1533.PubMedCentralPubMedGoogle Scholar
  27. 27.
    Jones, N. and Shenk, T. (1979) An adenovirus type 5 early gene function regulates expression of other early viral genes Proc Natl. Acad. Sci. USA 76, 3665–3669.PubMedCrossRefGoogle Scholar
  28. 28.
    Defer, C., Belin, M.-T., Caillet-Boudin, M.-L., and Boulanger, P. (1990) Human adenovirus-host cell interactions: comparative study with members of subgroups B and C J. Virol. 64, 3661–3673.PubMedCentralPubMedGoogle Scholar
  29. 29.
    Cotten, M., Wagner, E., Zatloukal, K., Phillips, S., Currel, D. T., and Birnstiel, M. L. (1992) High-efficiency receptor-mediated delivery of small and large (48 kilobase) gene constructs using the endosome-disruption activity of defective or chemically inactivated adenovirus particles Proc. Natl Acad. Sci. USA 89, 6094–6098.PubMedCrossRefGoogle Scholar
  30. 30.
    Felgner, P. L., Gadek, T R., Holm, M., et al. (1987) Lipofection: A highly efficient, lipid-mediated DNA-transfection procedure. Proc. Natl. Acad Sci USA 84, 7413–7417.PubMedCrossRefGoogle Scholar
  31. 31.
    Felgner, P. L., Holm, M., and Chan, H. (1989) Cationic liposome mediated transfection. Proc. West Pharmacol Soc. 32, 115–121.PubMedGoogle Scholar
  32. 32.
    Cristiano, R. J., Smith, L. C., Kay, M A, Brinkley, B R., and Woo, S L. (1993) Hepatic gene therapy: efficient gene delivery and expression in primary hepatocytes utilizing a conjugated adenovirus-DNA complex. Proc. Natl. Acad Sci USA 90, 11,548–11,552.PubMedCrossRefGoogle Scholar
  33. 33.
    Greber, U. F., Willetts, M., Webster, P., and Helenius, A. (1993) Stepwise dismantling of adenovirus 2 during entry into cells. Cell 75, 477–486.PubMedCrossRefGoogle Scholar
  34. 34.
    Cotten, M., Wagner, E., Zatloukal, K., and Birnstiel, M L. (1993) Chicken adenovirus (CELO Virus) particles augment receptor-mediated DNA delivery to mammalian cells and yield exceptional levels of stable transformants. J. Virol 67, 3777–3785.PubMedCentralPubMedGoogle Scholar
  35. 35.
    Wagner, E., Plank, C., Zatloukal, K., Cotten, M., and Birnstiel, M L. (1992) Influenza virus hemagglutinin HA-2 N-terminal fusogenic peptides augment gene transfer by transferrin-polylysine-DNA complexes. toward a synthetic virus-like gene-transfer vehicle. Proc. Natl. Acad Sci USA 89, 7934–7938.PubMedCrossRefGoogle Scholar
  36. 36.
    Michael, S. I., Huang, C.-H., Romer, M. U., Wagner, E., Hu, P-C., and Curie, D. T. (1993) Binding-incompetent adenovirus facilitates molecular conjugate-mediated gene transfer by the receptor-mediated endocytosis pathway J. Biol. Chem. 268, 6866–6869.PubMedGoogle Scholar
  37. 37.
    Michael, S. I. and Curiel, D. T. (1995) Strategies to achieve targeted gene delivery via the receptor-mediated endocytosis pathway. Gene Ther. 1, 223–232.Google Scholar
  38. 38.
    Curiel, T., Cook, D. R., Bogedain, C., Jilg, W., Harrison, G. S., Cotten, M., Curiel, D. T., and Wagner, E. (1994) Efficient foreign gene expression in Epstein-Barr virus-transformed human B-cells. Virology 198, 577–585.PubMedCrossRefGoogle Scholar
  39. 39.
    Batra, R. K., Johanning, F W., Wagner, E., Garver, R I., Jr., and Curiel, D. T. (1994) Receptor-mediated gene delivery employing lectin-binding specificity. Gene Ther 1, 255–260.PubMedGoogle Scholar
  40. 40.
    Morgan, R. A. and Anderson, W. F. (1993) Human gene therapy. Ann Rev. Biochem 62, 191–217.PubMedCrossRefGoogle Scholar
  41. 41.
    Gao, L., Wagner, E., Cotten, M., Agarwal, S., Harris, C., Romer, M., Miller, L., Hu, P.-C., and Curiel, D. (1993) Direct in vivo gene transfer to airway epithelium employing adenovirus-polylysine-DNA complexes Hum. Gene Ther 4, 17–24.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 1997

Authors and Affiliations

  • David T. Curiel
    • 1
  1. 1.University of AlabamaBirmingham

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