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Gene Therapy and Viral Vectors

  • Milton W. TaylorEmail author
Chapter
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Abstract

Gene therapy is the administration of a normal gene to replace a defective gene and thus cure or alleviate suffering from genetic diseases. Researchers are currently looking at a number of genetic diseases as targets, such as severe combined immunodeficiency (SCID), cystic fibrosis, and hemophilia, among others. In most cases, the genes are incorporated into a viral vector. These viruses may have a segment of genetic material removed and replaced with a “normal” gene, known as a “transgene.” The first clinical trial, which was a failure, was in 1980, when a small number of patients with thalassemia were treated with the human globin DNA. In 1995 the first successful trial was performed in children with a defect in adenosine deaminase (ADA) (SCID-syndrome). Treatment of SICD-X1 children, a condition leading to immunodeficiency, was also successful, but the retrovirus vector underwent integration into the host chromosome, resulting in a few cases of leukemia and one death. A large number of different viral vectors have been designed for use in gene therapy, including retrovirus, lentivirus, adenovirus and parvovirus. These are each discussed separately. Despite great efforts and a large number of clinical trials, only one vector system—AAV, Glybera—has been approved for gene therapy for the treatment of patients with lipoprotein lipase deficiency, a rare genetic disease.

Keywords

Cystic Fibrosis Gene Therapy Cystic Fibrosis Transmembrane Conductance Regulator Long Terminal Repeat Adenovirus Vector 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Taylor, M. W., Tokito, M., & Gupta, K. C. (1979). Lack of enhanced purine biosynthesis in HGPRT- and Lesch-Nyhan cells. Human Heredity, 29(3), 187–192.PubMedCrossRefGoogle Scholar
  2. 2.
    Taylor, M. W., Tokito, M. K., Gupta, K. C., & Pipkorn, J. (1978). Regulation of de novo purine biosynthesis in normal and 8-azaguanine-resistant Chinese hamster cells. Biochimica et Biophysica Acta, 517(1), 1–13.PubMedCrossRefGoogle Scholar
  3. 3.
    Verma, I. M. (1990). Gene therapy. Scientific American, 263(5), 68–72, 81–64.Google Scholar
  4. 4.
    Friedmann, T. (1992). A brief history of gene therapy. Nature Genetics, 2(2), 93–98.PubMedCrossRefGoogle Scholar
  5. 5.
    Sun, M. (1981). Cline loses two NIH grants. Science, 214(4526), 1220.PubMedCrossRefGoogle Scholar
  6. 6.
    Wade, N. (1981). Gene therapy caught in more entanglements. Science, 212(4490), 24–25.PubMedCrossRefGoogle Scholar
  7. 7.
    Wang, Q., & Taylor, M. W. (1993). Correction of a deletion mutant by gene targeting with an adenovirus vector. Molecular and Cellular Biology, 13(2), 918–927.PubMedCentralPubMedGoogle Scholar
  8. 8.
    Konan, V., Sahota, A., Graham, F. L., & Taylor, M. W. (1991). Transduction of the CHOaprt gene into mouse L cells using an adeno-5/APRT recombinant virus. Somatic Cell and Molecular Genetics, 17(4), 359–368.PubMedCrossRefGoogle Scholar
  9. 9.
    Culver, K., Cornetta, K., Morgan, R., Morecki, S., Aebersold, P., Kasid, A., et al. (1991). Lymphocytes as cellular vehicles for gene therapy in mouse and man. Proceedings of the National Academy of Sciences of the United States of America, 88(8), 3155–3159.PubMedCentralPubMedGoogle Scholar
  10. 10.
    Blaese, R. M., Culver, K. W., Miller, A. D., Carter, C. S., Fleisher, T., Clerici, M., et al. (1995). T lymphocyte-directed gene therapy for ADA-SCID: Initial trial results after 4 years. Science, 270(5235), 475–480.PubMedCrossRefGoogle Scholar
  11. 11.
    Cavazzana-Calvo, M., Hacein-Bey, S., de Saint Basile, G., Gross, F., Yvon, E., Nusbaum, P., et al. (2000). Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science, 288(5466), 669–672.PubMedCrossRefGoogle Scholar
  12. 12.
    Kay, M. A., Glorioso, J. C., & Naldini, L. (2001). Viral vectors for gene therapy: The art of turning infectious agents into vehicles of therapeutics. Nature Medicine, 7(1), 33–40.PubMedCrossRefGoogle Scholar
  13. 13.
    Escors, D., & Breckpot, K. (2010). Lentiviral vectors in gene therapy: Their current status and future potential. Archivum immunologiae et therapiae experimentalis, 58(2), 107–119.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Stratford-Perricaudet, L. D., Levrero, M., Chasse, J. F., Perricaudet, M., & Briand, P. (1990). Evaluation of the transfer and expression in mice of an enzyme-encoding gene using a human adenovirus vector. Human Gene Therapy, 1(3), 241–256.PubMedCrossRefGoogle Scholar
  15. 15.
    Rosenfeld, M. A., Siegfried, W., Yoshimura, K., Yoneyama, K., Fukayama, M., Stier, L. E., et al. (1991). Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo. Science, 252(5004), 431–434.PubMedCrossRefGoogle Scholar
  16. 16.
    Rosenfeld, M. A., Yoshimura, K., Trapnell, B. C., Yoneyama, K., Rosenthal, E. R., Dalemans, W., et al. (1992). In vivo transfer of the human cystic fibrosis transmembrane conductance regulator gene to the airway epithelium. Cell, 68(1), 143–155.PubMedCrossRefGoogle Scholar
  17. 17.
    Engelhardt, J. F., Simon, R. H., Yang, Y., Zepeda, M., Weber-Pendleton, S., Doranz, B., et al. (1993). Adenovirus-mediated transfer of the CFTR gene to lung of nonhuman primates: Biological efficacy study. Human Gene Therapy, 4(6), 759–769.PubMedCrossRefGoogle Scholar
  18. 18.
    Zabner, J., Couture, L. A., Gregory, R. J., Graham, S. M., Smith, A. E., & Welsh, M. J. (1993). Adenovirus-mediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosis. Cell, 75(2), 207–216.PubMedCrossRefGoogle Scholar
  19. 19.
    Crystal, R. G. (2012). The challenge of using gene- or cell-based therapies to treat lung disease. Molecular Therapy, 20(6), 1077–1078.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Hermonat, P. L., & Muzyczka, N. (1984). Use of adeno-associated virus as a mammalian DNA cloning vector: Transduction of neomycin resistance into mammalian tissue culture cells. Proceedings of the National Academy of Sciences USA, 81(20), 6466–6470.CrossRefGoogle Scholar
  21. 21.
    Asokan, A., Schaffer, D. V., & Samulski, R. J. (2012). The AAV vector toolkit: Poised at the clinical crossroads. Molecular Therapy, 20(4), 699–708.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Maclaren, R. E., Groppe, M., Barnard, A. R., Cottriall, C. L., Tolmachova, T., Seymour, L., Clark, K. R., During, M. J., Cremers, F. P., Black, G. C., et al. (2014). Retinal gene therapy in patients with choroideremia: Initial findings from a phase 1/2 clinical trial. The Lancet, 383, 1129–1137.Google Scholar
  23. 23.
    McClements, M. E., & MacLaren, R. E. (2013). Gene therapy for retinal disease. Translational Research: The Journal of Laboratory and Clinical Medicine, 161(4), 241–254.CrossRefGoogle Scholar
  24. 24.
    Garg, S. K., Lioy, D. T., Cheval, H., McGann, J. C., Bissonnette, J. M., Murtha, M. J., et al. (2013). Systemic delivery of MeCP2 rescues behavioral and cellular deficits in female mouse models of Rett syndrome. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 33(34), 13612–13620.CrossRefGoogle Scholar
  25. 25.
    Salmon, F., Grosios, K., & Petry, H. (2014). Safety profile of recombinant adeno-associated viral vectors: Focus on alipogene tiparvovec (Glybera((R))). Expert Review of Clinical Pharmacology, 7(1), 53–65.PubMedCrossRefGoogle Scholar
  26. 26.
    Peng, Z., Yu, Q., Bao, L. (2008). The application of gene therapy in China. IDrugs: The Investigational Drugs Journal, 11(5), 346–350.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Indiana UniversityBloomingtonUSA

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