Skip to main content
SpringerLink
Log in
Book cover

Medical Biomethods Handbook pp 625–638Cite as

Gene Therapy

Methods and Application

  • Protocol

  • 2028 Accesses

Part of the book series: Springer Protocols Handbooks ((SPH))

Abstract

Gene therapy represents a set of approaches to the treatment of diseases based on the transfer of genetic material (DNA) into an individual (or animal) and is defined as the use of nucleic acid transfer, either RNA or DNA, to treat or prevent a disease 1–3). The process involves a group of technologies that enable the intentional transfer of specific exogenous genetic information into cells and the application of these technologies for pharmaceutical development (4). The gene is delivered either by direct administration of a gene-containing virus or DNA to blood or tissue or indirectly through the introduction of cells manipulated in the laboratory to harbor foreign DNA. The idea behind this technology is to treat disease by the administration of DNA (rather than a drug), which will produce an appropriate amount of gene product (usually a protein) to correct the condition. In this process, only the somatic cells and not the germ cells (eggs and sperms) are the target; therefore, such gene transfer affects only the treated individual and not the offspring. In a broad sense therefore, gene therapy can be viewed as a natural progression in the application of biomedical science to medicine. It can be employed for the correction of an underlying pathophysiological condition and can offer a one-time cure for inherited disorders for which current therapeutic approaches are ineffective or where prospective treatment appear exceedingly low.

This is a preview of subscription content, log in via an institution.

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Crystal, R. G. (1995) Transfer of genes to humans: early lessons and obstacles to success. Science 270, 404–410.

    Article  PubMed  CAS  Google Scholar 

  2. Miller, A. D. (1992) Human gene therapy comes of age. Nature 357, 455–460.

    Article  PubMed  CAS  Google Scholar 

  3. Mulligan, R. C. (1993) The basic science of gene therapy. Science 260, 926–932.

    Article  PubMed  CAS  Google Scholar 

  4. Malone, E. W. (1999) Present and future status of gene therapy, in Advanced Gene Delivery (Rolland, A. ed.), Harwood Academic, London.

    Google Scholar 

  5. Schoefield, J. P. and Caskey, C. T. (1995) Non-viral approaches to gene therapy. Br. Med. Bull. 51(1), 56–71.

    Google Scholar 

  6. Arbones, M. L., Austin, H. A., Capon, D. J., and Greenburg, G. (1994) Gene targeting in normal somatic cells: inactivation of the interferon-γ-receptor in myoblasts. Nature Genet. 6, 90–96.

    Article  PubMed  CAS  Google Scholar 

  7. Dorin, J. R., Dickinson, P., Alton, E. W. F. W., et al (1992) Cystic fibrosis in the mouse by targeted insertional mutagenesis. Nature 359, 211–215.

    Article  PubMed  CAS  Google Scholar 

  8. Huxley, C. (1994) Mammalian artificial chromosomes: a new tool for gene transfer. Gene Ther. 1, 7–12.

    PubMed  CAS  Google Scholar 

  9. Orkins, S. H. and Motulsky, A. G. (1995) Report and recommendations of the panel to assess the NIH investigation in research on gene therapy. http://www.nih.gov/news/panelrep.html.

  10. Wang, A. Y., Peng, P. D., Ehrhardt, A., Storm, T. A., and Kay, M. (2004) Comparison of adenoviral and adeno-associated viral vectors for pancreatic gene delivery in vivo. Hum. Gene Ther. 15, 405–413.

    Article  PubMed  CAS  Google Scholar 

  11. Breyer, B., Jiang, W., Cheng, H., et al. (2001) Adenoviral vector-mediated gene transfer for human gene therapy. Curr. Gene Ther. 1, 149–162.

    Article  PubMed  CAS  Google Scholar 

  12. Guild, B. C., Finer, M. H., Housman, D. E., and Mulligan, R. C. (1988) Development of retrovirus vectors useful for expressing genes in cultured murine embryonal cells and hematopoietic cells in vivo. J. Virol. 62, 3795–3801.

    PubMed  CAS  Google Scholar 

  13. Miller, A. D., Miller, D. G., Garcia, J. V., and Lynch, C. M. (1993) Use of retroviral vectors for gene transfer and expression. Methods Enzymol. 217, 581–599.

    Article  PubMed  CAS  Google Scholar 

  14. Robbins, P. D. and Ghivizzani, S. C. (1998) Viral vectors for gene therapy. Pharmacol. Ther. 80(1), 35–47.

    Article  PubMed  CAS  Google Scholar 

  15. Kay, A. M., Liu, D., and Hoogerbrugge, M. (1997) Gene Therapy. Proc. Natl. Acad. Sci. USA 94, 12,744–12,746.

    Article  PubMed  CAS  Google Scholar 

  16. Duke University Institutional Biosafety Committee (1995) Retrovirus Vector Guidelines. http://www2.duke.edu/depts/gc/txtfiles/ibcretro.html.

  17. Graham, F. L. and Prevec, L. (1995) Methods for construction of adenovirus vectors. Mol. Biotechnol. 3, 207–220.

    Article  PubMed  CAS  Google Scholar 

  18. Wivel, N. A. and Wilson, J. M. (1998) Methods of gene delivery. Gene Ther. 12(3), 483–499.

    CAS  Google Scholar 

  19. Yang, Y., Haecker, S. E., Su, Q., and Wilson, J. (1996) Immunology of gene therapy with adenoviral vectors in mouse skeletal muscle. Hum. Mol. Genet. 5(11), 1703–1712.

    Article  PubMed  CAS  Google Scholar 

  20. Yang, Y. and Wilson, J. M. (1995) Clearance of adenovirus-infected hepatocytes by MHC class Irestricted CD4+ CTLs in vivo. Immunology 155(5), 2564–2570.

    CAS  Google Scholar 

  21. Mack, C. A., Song, W. R., Carpenter, H., et al. (1997) Circumvention of anti-adenovirus neutralizing immunity by administration of an adenoviral vector of an alternate serotype. Hum. Gene Ther. 8, 99–109.

    Article  PubMed  CAS  Google Scholar 

  22. Stilwel, J. L., McCarty, D. M., Negishi, A., Superfine, R., and Samulski, R. J. (2003) Development and characterization of novel empty capsids and their impact on cellular gene expression. J. Virol. 77(23), 12,881.

    Google Scholar 

  23. Gao, G., Alvira, M. R., Wang, L., Calcedo, R., Johnston, J., and Wilson, J. M. (2002) Novel adenoassociated viruses from rhesus monkeys as vectors for human gene therapy. Proc. Natl. Acad Sci USA 99, 11,854–11,859.

    Article  PubMed  CAS  Google Scholar 

  24. Grimm, D. and Kay, M. A. (2003) From virus evolution to vector revolution: use of naturally occurring serotypes of adeno-associated virus (AAV) as novel vectors from human gene therapy. Curr-Gene Ther. 3, 281–304.

    Article  PubMed  CAS  Google Scholar 

  25. Flotte, T., Agarwal, A., Wang, J., et al. (2001) Efficient ex vivo transduction of pancreatic islet cells with recombinant adeno-associated virus vectors. Diabetes 50, 515–552.

    Article  PubMed  CAS  Google Scholar 

  26. McCart, J. A., Puhlmann, M., Lee, J., et al. (2000) Complex interactions between the replicating oncolytic effect and the enzyme/prodrug effect of vaccinia-mediated tumor regression. Gene Ther. 7, 1217–1223.

    Article  PubMed  CAS  Google Scholar 

  27. Hu, Y., Lee, J., McCart, J. A., et al. (2001) Yaba-like disease virus: an alternative replicating poxvirus vector for cancer gene therapy. J. Virol. 75(21), 10,300–10,308.

    Article  PubMed  CAS  Google Scholar 

  28. Ribas, A., Butterfield, L. H., and Economou, J. S. (2000) Genetic immunotherapy for cancer. Oncologist 5, 87–98.

    Article  PubMed  CAS  Google Scholar 

  29. Springer, C. J. and Niculescu-Duvaz, I. (2000) Prodrug-activating systems in suicide gene therapy. J. Clin. Invest. 105, 1161–1167.

    Article  PubMed  CAS  Google Scholar 

  30. Xu G. and McLeod H. L. (2001) Strategies for enzyme/prodrug cancer therapy. Clinical Cancer Research 7, 3314–3324.

    PubMed  CAS  Google Scholar 

  31. Wolff, J. A., Malone, R. W., Williams P., et al. (1990) Direct gene transfer into mouse muscle in vivo. Science 247, 1465–1468.

    Article  PubMed  CAS  Google Scholar 

  32. Liu, F., Liang, K. W., and Huang, L. (2001) Systemic administration of naked DNA: gene transfer to skeletal muscle. Mol. Intervent. 3, 168–172.

    Google Scholar 

  33. Marshall, D. J. and Leiden, J. M. (1998) Recent advances in skeletal-muscle-based gene therapy. Curr. Opin. Genet. Dev. 8, 360–365.

    Article  PubMed  CAS  Google Scholar 

  34. Wolff, J. A., Ludtke, J. J., Acsadi, G., Williams, P. and Jani, A. (1992) Long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum. Mol. Genet. 1(6), 363–369.

    Article  PubMed  CAS  Google Scholar 

  35. Doh, S., G., Vahlsing, H. L., Hartikka, J., Liang, X., and Manthorpe, M. (1997) Spatial-temporal patterns of genes expression in mouse skeletal muscle after injection of lacZ plasmid DNA. Gene Ther. 4(7), 648–663.

    Article  PubMed  CAS  Google Scholar 

  36. Herweijer, H. and Wolff, J. A. (2003) Progress and prospects: naked DNA gene transfer and therapy. Gene Ther. 10, 453–458.

    Article  PubMed  CAS  Google Scholar 

  37. Eastman, S. J., et al., (2002) Development of catheter-based procedures for transducing the isolated rabbit liver with plasmid DNA. Hum. Gene Ther. 13, 2065–2077.

    Article  PubMed  CAS  Google Scholar 

  38. Zhang, G., Budker, V., Williams, P., Subbotin, V., and Wolff J. A. (2001) Efficient expression of naked DNA delivered intraarterially to limb muscles of nonhuman primates. Hum. Gene Ther. 12, 427–438.

    Article  PubMed  CAS  Google Scholar 

  39. McKay, M. J. and Gaballa, M. A. (2001) Gene transfer therapy in vascular disease. Cardiovasc. Drug Rev. 19(3), 245–62.

    Article  PubMed  Google Scholar 

  40. Williams, R. S., Johnston, S. A., Riedy, M., DeVit, J. M., McElligott, S. G., Sanford, J. C. (1991) Introduction of foreign genes into tissues of living mice by DNA-coated microprojectiles. Proc. Natl. Acad. Sci. USA 88, 2726–2730.

    Article  PubMed  CAS  Google Scholar 

  41. Donnelly, J. J., Ulmer, J. B., and Liu, M. A. (1998) DNA vaccines. Dev. Biol. Stand. 95, 43–53.

    PubMed  CAS  Google Scholar 

  42. Sato, Y., Roman, M., Tighe, H, et al. (1996) Immunostimulatory DNA sequences necessary for effective intradermal gene immunization. Science 273(5273), 352–354.

    Article  PubMed  CAS  Google Scholar 

  43. Hanlon, L. and Argyle, D. J. (2001) The science of DNA vaccination. Infect. Dis. Rev. 3(1), 2–12.

    Google Scholar 

  44. Felgner, P. L., Gadek, T. R., Holm M., et al. (1987) Lipofectin: a highly efficient, lipid-mediated DNA-transfection procedure. Proc. Natl. Acad. Sci. USA 84, 7413–7417.

    Article  PubMed  CAS  Google Scholar 

  45. Nabel G. J., Nabel E. G., Yang Z. Y., et al. (1993) Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity and lack of toxicity in humans. Proc. Natl. Acad. Sci. USA 90, 11307–11311.

    Article  PubMed  CAS  Google Scholar 

  46. Plank, C., Mechtler, K., Szoka, F. C., and Wagner, E. (1996) Activation of the complement system by synthetic DNA complexes: a potential barrier for intravenous gene delivery. Hum. Gene Ther. 7, 1437–1446.

    Article  PubMed  CAS  Google Scholar 

  47. Zabner, J., Fasbender, A. J., Moninger, T., Poellinger, K. A., and Welsh, M. J. (1995) Cellular and molecular barriers to gene transfer by a cationic lipid. J. Biol. Chem. 270, 18,997–19,007.

    Article  PubMed  CAS  Google Scholar 

  48. Pedroso de Lima, M. C., Neves, S., Filipe, A., Duzgunes, N., and Simoes, S. (2003) Cationic liposomes for gene delivery: from biophysics to biological applications. Curr. Med. Chem. 10(14), 1221–1231.

    Article  Google Scholar 

  49. Carrière, M., Escriou, V., Savarin, A., and Scherman, D. (2003) Coupling of importin beta binding peptide on plasmid DNA: transfection efficiency is increased by modification of lipoplex’s physicochemical properties. BMC Biotechnol. http://www.biomedcentral.com/1472-6750/3/14.

  50. Nchinda, G., Überla, K., and Zschörnig, O. (2002) Characterization of cationic lipid DNA transfection complexes differing in susceptibility to serum inhibition. http://biomedcentral.com/1472-6750/2/12.

  51. Almofti, M. R., Harashima, H., Shinohara, Y., Almofti, A., Li, W., and Kiwada, H. (2003) Lipoplex size determines lipofection efficiency with or without serum. Mol. Membr. Biol. 20(1), 35–43.

    Article  PubMed  CAS  Google Scholar 

  52. Caracciolo, G., Pozzi, D., Caminiti, R., and Congiu Castellano, A. (2003) Structural characterization of a new lipid/DNA complex showing selective transfection efficiency in ovarian cancer cells. Eur. Phys. J. E: Soft Matter 10(4), 331–336.

    Article  PubMed  CAS  Google Scholar 

  53. Somiari, S., Glasspool-Malone, J., Drabick, J. J., et al. (2000) Theory and in vivo application of electroporative gene delivery. Mol. Ther. 2(3), 178–187.

    Article  PubMed  CAS  Google Scholar 

  54. Vanbever, R., Leroy, M. A., and Preat, V. (1998) Transdermal permeation of neutral molecules by skin electroporation. J. Control. Release 54, 243–250.

    Article  PubMed  CAS  Google Scholar 

  55. Hartika, J., Sukhu, L., Buchner, C., et al. (2001) Electroporation-facilitated delivery of plasmid DNA in skeletal muscle: plasmid dependence of muscle damage and effect of poloxamer 188. Mol. Ther. 4, 407–415.

    Article  Google Scholar 

  56. Terada Ytanaka, H., Okado, T., Inoshila, S., Kuwahara, M., Akiba, T., Sasaki, S., and Marumo, F. (2001) Efficient and ligand-dependent regulated erythropoietin production by naked DNA injection and in vivo electroporation. Am. J. Kidney Dis. 38, S50–S53.

    Article  Google Scholar 

  57. Vilquin J. T. Kennel Pf, Paturneau-Jouas M., Chapdelaine P., Boissel N., Delaere P., Tremblay J. P., Scherman D., Fiszman M. Y. (2001) Electrotransfer of naked DNA in the skeletal muscles of animal models of muscular dystrophyies. Gene Ther. 8, 1097–1107.

    Article  PubMed  CAS  Google Scholar 

  58. Swisher, S. G., Roth, J. A., Nemunaitis J., et al (1999) Adenovirus-mediated p53 gene transfer in advanced non-cell lung cancer. J. Natl. Cancer Inst. 5(91), 763–771.

    Google Scholar 

  59. Marshall, E. (2000) Gene therapy on trial. Science 288, 951–957.

    Article  PubMed  CAS  Google Scholar 

  60. Cavazzana-Calvo, M., Hacein-Bey, S., de Saint Basile, G., et al (2000) Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 28,288(5466), 627–629.

    Google Scholar 

  61. Hacein-Bey-Abina,. S., Von Kalle, C., Schmidt, M., et al., (2003) LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 17,302(5644), 400–401.

    Google Scholar 

  62. Hyde, S. C., Southern, K. W., Gilead U., et al. (2000) Repeat administration of DNA/liposomes to the nasal epithelium of patients with cystic fibrosis. Gene Ther. 7, 1156–1165.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Windber Research Institute, Winbder, PA

    Stella B. Somiari

Authors
  1. Stella B. Somiari
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Hertfordshire, Hatfield, UK

    John M. Walker  & Ralph Rapley  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Somiari, S.B. (2005). Gene Therapy. In: Walker, J.M., Rapley, R. (eds) Medical Biomethods Handbook. Springer Protocols Handbooks. Humana Press. https://doi.org/10.1385/1-59259-870-6:625

Download citation

  • DOI: https://doi.org/10.1385/1-59259-870-6:625

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-288-9

  • Online ISBN: 978-1-59259-870-0

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation