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Stable in vivo gene transduction via a novel adenoviral/retroviral chimeric vector

Nature Biotechnology volume 15, pages 866–870 (1997)Cite this article

Abstract

Gene therapy to correct defective genes requires efficient gene delivery and long-term gene expression. The available vector systems have not allowed the simultaneous achievement of both goals. We have developed a chimeric viral vector system that incorporates favorable aspects of both adenoviral and retroviral vectors. Adenoviral vectors induce target cells to function as transient retroviral producer cells in vivo. The progeny retroviral vector particles are then able to stably transduce neighboring cells. In this system, the nonintegrative adenoviral vector is rendered functionally integrative via the intermediate generation of a retroviral producer cell. The chimeric vectors may allow realization of the requisite goals for specific gene-therapy applications.

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References

  1. Anderson, W.F. 1984. Prospects for human gene therapy. Science 226: 401–409.

    CAS  PubMed  Google Scholar 

  2. Miller, A.D. 1990. Progress toward human gene therapy. Blood 76: 271–278.

    CAS  PubMed  Google Scholar 

  3. Felgner, P.L. and Rhodes, G. 1991. Gene therapeutics. Nature 349: 351–352.

    Article  CAS  PubMed  Google Scholar 

  4. Roemer, K. and Friedmann, T. 1992. Concepts and strategies for human gene therapy. Eur. J. Biochem. 208: 211–225.

    Article  CAS  PubMed  Google Scholar 

  5. Hannania, E.G., Kavanagh, J., Hortobagyi, G., Giles, R.E., Champlin, R., and Deisseroth, A.B. 1995. Recent advances in the application of gene therapy to human disease. Am. J. Med. 99: 537–552.

    Article  Google Scholar 

  6. Klein, H.G. 1994. Cellular gene therapy: An overview. J. Clin. Apheres. 9: 139–141.

    Article  CAS  Google Scholar 

  7. Dai, Y., Roman, M., Naviaux, R.K., and Verman, I.M. 1992. Gene therapy via primary myoblasts: Long-term expression of fact IX protein following transplantation in vivo. Proc. Natl. Acad. Sci. USA 89: 10892–10895.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wilson, J.M. 1995. Gene therapy for cystic fibrosis: Challenges and future directions. J. Clin. Invest. 96: 2547–2554.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rosenfeld, M.A. and Collins, F.S. 1996. Gene therapy for cystic fibrosis. Chest 109: 241–252.

    Article  CAS  PubMed  Google Scholar 

  10. Fox, J.C. 1996. Cardiovascular gene therapy: Current concepts. Therapeutic Drug Monitoring 18: 410–422.

    Article  CAS  PubMed  Google Scholar 

  11. Lozier, J.N. and Brinkjous, K.M. 1994. Gene therapy and the hemophilias. JAMA 271: 47–51.

    Article  CAS  PubMed  Google Scholar 

  12. Haffe, H.A., Danel, C., Longenecker, G., Metzger, M., Setoguchi, Y., Rosenfeld, M.A., et al. 1992. Adenovirus-mediated in vivo gene transfer and expression in normal rat liver. Nature Genetics 1: 372–378.

    Article  Google Scholar 

  13. Smith, T.A., Mehaffey, M.G., Kayda, D.B., Saunders, J.M., Yei, S., Trapnell, B.C. et al. 1993. Adenovirus-mediated expression of therapeutic plasma levels of human factor IX in mice. Nature Genetics 5: 397–402.

    Article  CAS  PubMed  Google Scholar 

  14. Morsy, M.A., Alford, E.L., Bett, A., Graham, F.L., Caskey, C.T. 1993. Efficient adenoviral-mediated ornithine transcarbamylase expression in deficient mouse and human hepatocytes. J. Clin. Invest. 92: 1580–1586.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Herz, J. and Gerard, R.D. 1993. Adenovirus-mediated transfer of low density lipoprotein receptor gene acutely accelerates cholersterol clearance in normal mice. Proc. Natl. Acad. Sci. USA 90: 2812–2816.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kozarsky, K., Grossman, M., and Wilson, J.M. 1993. Adenovirus-mediated correction of the genetic defect in hepatocytes from patients with familial hypercholesterolemia. Somatic Cell Molec. Gen. 19: 449–458.

    Article  CAS  Google Scholar 

  17. Ishibashi, S., Brown, M.S., Goldstein, J.L., Gerard, R.D., Hammer, R.E., and Herz, J. 1993. Hypercholesterolemia in low density lipoprotein receptor knockout mice and its reversal by adenovirus-mediated gene delivery. J. Clin. Invest. 92: 883–893.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kozarsky, K.F., Jooss, K., Donahee, M., Strauss, J.F. III, and Wilson, J.M. 1996. Effective treatment of familial hypercholesterolaemia in the mouse model using adenovirus-mediated transfer of the VLDL receptor gene. Nature Genetics 13: 54–62.

    Article  CAS  PubMed  Google Scholar 

  19. Ye, X., Robinson, M.B., Batshaw, M.L., Furth, E.E., Smith, I., and Wilson, J.M. 1996. Prolonged metabolic correction in adult ornithine transcarbamy-lase-deficient mice with adenoviral vectors. J. Biol. Chem. 271: 3639–3646.

    Article  CAS  PubMed  Google Scholar 

  20. Yang, Y., Nunes, F.A., Berencsi, K., Furth, E.E., Gonczol, E., and Wilson, J.M. 1994. Cellular immunity to viral antigens limits E1-deleted adenoviruses for gene therapy. Proc. Natl. Acad. Sci. USA 91: 4407–4411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yang, Y. and Wilson, J.M. 1995. Clearance of adenovirus-infected hepatocytes by MHC class I-restricted CD4+ CTLs in vivo. J. Immunol. 156: 2564–2570.

    Google Scholar 

  22. Yang, Y., Ertle, H.C., and Wilson, J.M. 1995. MHC class I-restricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with E1-deleted recombinant adenoviruses. Immunity 1: 433–442.

    Article  Google Scholar 

  23. Yang, Y., Li, Q., Ertl, H.C., and Wilson, J.M. 1995. Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses. J. Virol. 69: 2004–2015.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Ferry, N., Duplessis, O., Houssin, D., Danos, O., and Heard, J.-M. 1991. Retroviral-mediated gene transfer in hepatocytes in vivo. Proc. Natl. Acad. Sci. USA 88: 8377–8381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kolodka, T.M., Finegold, M., and Woo, S.L.C. 1993. Hepatic gene therapy: Efficient retroviral-mediated gene transfer into rat hepatocytes in vivo. Somatic Cell Molec. Gen. 19: 491–497.

    Article  CAS  Google Scholar 

  26. Dunckley, M.G., Wells, D.J., Welsh, F.S., and Dickson, G. 1993. Direct retroviral-mediated transfer of a dystrophin minigene into mdx mouse muscle in vivo. Human Molecular Genetics 2: 717–723.

    Article  CAS  PubMed  Google Scholar 

  27. Moscioni, A.D., Rozga, J., Neuzil, D.F., Overell, R.W., Holt, J.T., and Demetriou, A.A. 1993. In vivo regional delivery of retrovirally mediated foreign genes to rat liver cells: Need for partial hepatectomy for succcessful foreign gene expression. Surgery 113: 304–311.

    CAS  PubMed  Google Scholar 

  28. Kolodka, T.M., Finegold, M., and Woo, S.L.C. 1993. Hepatic gene therapy: Efficient retroviral- mediated gene transfer into rat hepatocytes in vivo. Somatic Cell Molec. Gen. 19: 491–497.

    Article  CAS  Google Scholar 

  29. Ram, Z., Walbridge, S., Oshiro, E.M., Viola, J.J., Chiang, Y., Mueller, S.N., et al. 1994. Intrathecal gene therapy for malignant leptomeningeal neoplasia. Cancer Res. 54: 2141–2145.

    CAS  PubMed  Google Scholar 

  30. Short, M.P., Choi, B.C., Lee, J.K., Malick, A., Breakefield, X.O., and Martuza, R.L. 1990. Gene delivery to glioma cells in rat brain by grafting of a retrovirus packaging cell line. J. Neurosci. Res. 27: 427–433.

    Article  CAS  PubMed  Google Scholar 

  31. Culver, K.W., Ram, Z., Walbridge, S., Ishii, H., Oldfield, E.H., and Blaese, R.M. In vivo gene transfer with retroviral vector-producer cells for treatment of experimental brain tumors. Science 256: 1550–1552.

    Article  CAS  PubMed  Google Scholar 

  32. Takamiya, Y., Short, M.P., Moolten, F.L., Fleet, C., Mineta, T., Breakefield, X.O., and Martuza, R.L. 1993. An experimental model of retrovirus gene therapy for malignant brain tumors. J. Neurosurg. 79: 104–110.

    Article  CAS  PubMed  Google Scholar 

  33. Ram, Z., Culver, K.W., Walbridge, S., Blaese, R.M., and Oldfield, E.H. 1993. In situ retroviral-mediated gene transfer for the treatment of brain tumors in rats. Cancer Res. 53: 83–88.

    CAS  PubMed  Google Scholar 

  34. Ram, Z., Culver, K.W., Walbridge, S., Frank, J.A., Blaese, R.M., and Oldfield, E.H. 1993. Toxicity studies of retroviral-mediated gene transfer for the treatment of brain tumors. J. Neurosurg. 79: 400–407.

    Article  CAS  PubMed  Google Scholar 

  35. Vile, R.G. and Russell, S.J. 1995. Retroviruses as vectors. Brit. Med. Bull. 51: 12–30.

    Article  CAS  PubMed  Google Scholar 

  36. Miller, A.D. 1992. Retroviral vectors. Current topics in microbiology and immunology 158: 1–24.

    CAS  PubMed  Google Scholar 

  37. Rollins, S.A., Birks, C.W., Setter, E., Squinto, S.P., and Rother, R.P. 1996. Retroviral vector producer cell killing in human serum in mediated by natural antibody and complement: Strategies for evading the humoral immune response. Human Gene Therapy 7: 619–626.

    Article  CAS  PubMed  Google Scholar 

  38. Pear, W.S., Nolan, G.P., Scott, M.L., and Baltimore, D. 1993. Production of high-titer helper-free retroviruses by transient transfection. Proc. Natl. Acad. Sci. USA 90: 8392–8396.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Flamant, F., Demeneix, B., Benoist, C., Markossian-Belin, S., and Samarut, J. 1994. Virofection: A new procedure to achieve stable expression of genes transferred into early embryos. Int. J. Dev. Biol. 38: 751–757.

    CAS  PubMed  Google Scholar 

  40. Morling, F.J. and Russell, S.J. 1995. Enhanced transduction efficiency of retroviral vectors coprecipitated with calcium phosphate. Gene Therapy 2: 504–508.

    CAS  PubMed  Google Scholar 

  41. Flamant, F. and Samarut, J. 1995. Virofection: A one-step procedure for using replication-defective retrovirus vectors. Virology 211: 234–240.

    Article  CAS  PubMed  Google Scholar 

  42. Finer, M.H., Dull, T.J., Qin, L., Farson, D., and Roberts, M.R. 1994. kat: A high efficiency retroviral transduction system for primary human T lymphocytes. Blood 83: 43–50.

    CAS  PubMed  Google Scholar 

  43. Noguiez-Hellin, P., Robert-Le Meur, M., Salzmann, J.-L., and Klatzmann, D., 1996. Plasmoviruses: Nonviral/viral vectors for gene therapy. Proc. Natl. Acad. Sci. USA 93: 4175–1780.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bett, A.J., Haddara, W., Prevec, L., Graham, F.L. 1994. An efficient and flexible system for-construction of adenovirus vectors with insertions or deletions in early regions 1 and 3. Proc Natl Acad Sci USA 91: 8802–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Curiel, D.T. 1994. High-efficiency gene transfer employing adenovirus-polylysine-DNA complexes. Natural Immunity 13: 141–164.

    CAS  PubMed  Google Scholar 

  46. Fisher, K.J., Kelley, W.M., Burda, J.F., and Wilson, J.M. 1996. A novel adenovirus-adeno-associated virus hybrid vector that displays efficient rescue and delivery of the AAV genome. Human Gene Therapy 7: 2079–2087.

    Article  CAS  PubMed  Google Scholar 

  47. Haapala, D.K., Robey, W.G., Oroszlan, S.D., and Tsai, W.P. 1985. Isolation from cats of an endogenous type C virus with a novel envelope. J. Virology 53: 827–833.

    CAS  PubMed  PubMed Central  Google Scholar 

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Author notes

  1. David T. Curiel: e-mail: dcuriel@gtp.ccc.uab.edu.

Authors and Affiliations

  1. Gene Therapy Program, University of Alabama at Birmingham, Birmingham, AL, 35294

    Meizhen Feng, William H. Jackson Jr., Corey K. Goldman, Claudine Rancourt, Minghui Wang & David T. Curiel

  2. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294

    Gene Siegal

  3. Virology Laboratory, MA Bioservices, Inc., Rockville, MD, 20850

    Sandra K. Dusing

Authors
  1. Meizhen Feng
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Feng, M., Jackson, W., Goldman, C. et al. Stable in vivo gene transduction via a novel adenoviral/retroviral chimeric vector. Nat Biotechnol 15, 866–870 (1997). https://doi.org/10.1038/nbt0997-866

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