Skip to main content
Book cover

Gene Therapy pp 61–71Cite as

Liposomes in Gene Therapy

  • Chapter

Abstract

Recent advances in molecular and cellular biology have upgraded the idea of clinical human gene therapy from mere speculation to a clear possibility. The concept of gene therapy is about attacking human disease at the level of underlying genetic mechanisms and defects. As Aposhian stated, in 1970, “If one considers the purpose of a drug to restore the normal function of some particular process in the body, then DNA would be considered the ultimate drug” [1]. Implementation of the concept of DNA as an ultimate drug has involved, among other important aspects, development of gene delivery vehicles, optimization of gene delivery methods and studies to determine stability and expression of the desired gene. In this regard, a number of gene delivery systems, as described in earlier chapters, have been tried. Use of liposomes as a gene transfer method is the focus of this chapter but representation of their role deserves a detailed introduction. Therefore this article describes their preparation and role as a vehicle to deliver DNA molecules and the possible delivery mechanism of encapsulated materials.

Keywords

  • Gene Therapy
  • Gene Delivery
  • Cationic Liposome
  • Sendai Virus
  • Liposome Preparation

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.

This is a preview of subscription content, access via your institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-3-0348-7011-5_5
  • Chapter length: 11 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   109.00
Price excludes VAT (USA)
  • ISBN: 978-3-0348-7011-5
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   149.99
Price excludes VAT (USA)
Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aposhian, H. V. (1970) The use of DNA for gene therapy-the need, experimental approach, and implications. Perspec. Biol. Med. 14: 987–1008.

    Google Scholar 

  2. New, R. R. C. (1995) Influence of liposome characteristcs on their properties and fate. In: The liposomes. CRC Press Inc. Boca Raton, Florida, pp 3–20.

    Google Scholar 

  3. New, R. R. C. (1990) Preparation of liposomes. In: R. R. C. New (ed.), Liposomes A Practical Approach. IRL Press. Oxford university Press, New York, pp 3–20.

    Google Scholar 

  4. Batzri, S. and Korn, E. D. (1973) Single bilayer liposomes prepared without sonication. Biochim. Biophys. Acta 298: 1015–1019.

    CrossRef  PubMed  CAS  Google Scholar 

  5. Gregoriadis, G., Florence, A. T. (1993) Liposome technology, 2nd edition, RCR press Inc. Boca Raton.

    Google Scholar 

  6. Feigner, P. L., Gadek, T. R., Holm, M., Roman, R., Chan, H. W., Wenz, M., Northop, J. P., Ringold, G. M. and Danielson, M. (1987) Lipofectin: A highly efficient, lipid-mediated DNA-transfection procedure. Proc. Natl. Acad. Sci. USA 84: 7413–7417.

    CrossRef  Google Scholar 

  7. Remy, J. S., Sirlin, C. and Behr, J. P. (1995) Gene transfer with cationic amphiphiles. In: The liposomes. CRC Press Inc. Boca Raton, Florida, pp. 159–170.

    Google Scholar 

  8. Leventis, R. and Silvius, J. R. (1990) Interaction of mammalian cells with lipid dispersions containing novel metabolizable cationic amphiphiles. Biochim. Biophys. Acta 1023: 124–132.

    CrossRef  PubMed  CAS  Google Scholar 

  9. Tirrell, D., A.,Takigawa, D., Y. and Seki, K. (1985) pH-sensitization of phospholipid vesicles via complexation with synthetic poly(carboxylic acids). Ann. N.Y. Acad. Sci. 446: 237.

    Google Scholar 

  10. Uster, P. S. and Deamer, D. (1985) pH-dependent fusion of liposomes using titrable poly-cations Biochemistry 24: 1–8.

    Google Scholar 

  11. Parente, R., A., Nir, S. and Szoka, E C. (1988) pH-dependent fusion of phosphatidylcholine small vesicles: induction by a synthetic amhiphilic peptide J.Biol. Chem. 263: 4724.

    Google Scholar 

  12. Legendre, J. -Y. and Szoka, F. C., Jr. (1992) Delivery of piasmid DNA into mammalian cell lines using pH-sensitive liposomes: Comparison with cationic liposomes. Pharm. Res. 9: 1235–1242.

    CrossRef  PubMed  CAS  Google Scholar 

  13. Feigner, P. L. and Ringold, G. M. (1989) Cationic liposome-mediated transfection. Nature 337: 387–388.

    CrossRef  Google Scholar 

  14. Behr, J. P. (1986) DNA strongly binds to micelles and vesicles containing lipopolyamines or lipointercalatants. Tet. Lett. 27: 5861–64.

    CrossRef  CAS  Google Scholar 

  15. Haywood, A. M. (1975) `Phagocytosis’ of Sendai virus by model membranes. J. Gen. Virol. 29: 63–68.

    Google Scholar 

  16. Friend, D. S., Debs, R. J. and Duzgunes, N. (1990) Interactions between DOTMA liposomes, CV-1 and U937 cells and their isolated nuclei. 30th annual meeting of the American Society for Cell Biology, San Diego. J. Cell Biol. 111: 663.

    CrossRef  Google Scholar 

  17. Mellman, I., Fuchs, R. and Helenius, A. (1986) Acidification of the endocytic and exocytic pathways. Ann.Rev. Biochem. 55: 663–700.

    CrossRef  PubMed  CAS  Google Scholar 

  18. Schmid, S. L., Fuchs, R., Male, P. and Mellman, I. (1988) Two distinct subpopulations of endosomes ionvolved in membrane recycling and transport to lysosomes. Cell 52: 73–83.

    CrossRef  PubMed  CAS  Google Scholar 

  19. Harding, C. V., Collins, D., Slot, J. W., Geuze, H. J. and Unanue, E. R. (1991) Liposomeencapsualted antigens are processed in lysosomes, recycled and presented to T cells. Cell 64: 393.

    CrossRef  PubMed  CAS  Google Scholar 

  20. Hara, T., Kuwasawa, H., Aramak, Y., Takada, S., Koike, K., Ishidate, K., Kato, H. and Tsuchiya, S. (1996) Effects of fusogenic and DNA-binding amphilphilic compounds on the receptor mediated gene transfer into hepatic cells by asialofetuin-labeled liposomes. Biochem. Biophys. Acta-Biomemb. 1278N1: 51–58.

    Google Scholar 

  21. Cristiano R. J., and Curiel, D. T. (1996) Strategies to accomplish gene delivery via the receptor-mediated endocytosis pathway. Cancer Gene Ther. 3: 49–57.

    PubMed  CAS  Google Scholar 

  22. Canonico, A. E., Conary, J. T., Meyrick, B., Brigham, K. L. (1994) Aerosol and intravenous transfection of human alpha-1 antitrypsin gene to lungs of rabbits. Amer. J. Respir. Cell Mol. Biol. 10: 24–29.

    CAS  Google Scholar 

  23. Canonico, A. E., Plitman, J. D., Conary, J. T., Meyrick, B. O. and Brigham, K. L. (1994) No lung toxicity after repeated aerosol or intravenous delivery of plasmid-cationic liposome complexes. J. Appl. Physiol. 77: 415–419.

    PubMed  CAS  Google Scholar 

  24. Nabel, E. G., Yang, Z. Y., Muller, D., Chang, A. E., Gao, X., Huang, L., Cho, K., Nabel, G. J. (1994) Safety and toxicity of catheter gene delivery to the pulmonary vasculature in a patient with metastatic melanoma. Hum. Gene Ther. 5: 1089–1094.

    CrossRef  PubMed  CAS  Google Scholar 

  25. Yoshimura, K., Rosenfeld, M. A., Nakamura, H., Scherer, E. M., Pavirani, A., Lecocq, J. P., Crystal, R. G. (1992) Expression of the human cystic fibrosis transmembrane conductance regulator gene in the mouse lung after in vivo intratracheal plasmid mediated gene transfer. Nucl. Acid. Res. 20: 3233–3240.

    CrossRef  CAS  Google Scholar 

  26. Zhu, N., Liggitt, D., Liu, Y., Debs, R. (1993) Systemic gene expression after intravenous DNA delivery into adult mice. Science 261: 209–211.

    CrossRef  PubMed  CAS  Google Scholar 

  27. Hyde, S. C., Gill, D. R., Higgins, C. E, Trezise, A. E. O., Macvinish, L. J., Cuthbert, A. W., Ratcliff, R., Evans, M. J., Colledge, W. H. (1993) Correction of the ion-transport defect in cystic fibrosis transgenic mice by gene therapy. Nature 362: 250–255.

    CrossRef  PubMed  CAS  Google Scholar 

  28. Logan, J. J., Bebok, Z., Walker, L. C., Peng, S. Y., Feigner, P. L., Siegal, G. P., Frizzell, R. A., Dong, J. Y., Howard, M., Matalon, S., Lindsey, J. R., Duvall, M. and Sorscher, E. J. (1995) Cationic lipids for reporter gene and CFTR transfer to pulmonary epithelium. Gene Ther. 2: 38–49.

    PubMed  CAS  Google Scholar 

  29. Stribling, R., Brunette, E., Liggitt, D., Gaensler, K., Debs, R. (1992) Aerosol gene delivery in vivo. Proc Natl. Acad. Sci. USA 89: 11277–11281.

    CrossRef  CAS  Google Scholar 

  30. Conary, J. T., Parker, R. E., Christman, B. W., Faulks, R. D., King, G. A., Meyrick, B. O., Brigham, K. L. (1994) Protection of rabbit lungs from endotoxin injury by in vivo hyperexpression of the prostaglandin G/H synthase gene. J. Clin. Invest. 93: 1834–1840.

    CrossRef  PubMed  CAS  Google Scholar 

  31. Plautz, G. E., Yang, Z. Y., Wu BY, Gao, X., Huang, L. and Nabel GJ (1993) Immunotherapy of malignancy by in vivo gene transfer into tumors. Proc Natl Acad Sci. USA 90: 4645–4649.

    CrossRef  PubMed  CAS  Google Scholar 

  32. Nabel, G. J., Nabel, E. G., Yang, Z. Y., Fox, B. A., Plautz, G. E., Gao, X., Huang, L., Shu, S., Gordon, D., Chang, A. E. (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.

    CrossRef  PubMed  CAS  Google Scholar 

  33. Hofland, H. and Huang, L. (1995) Inhibition of human ovarian-carcinoma cell proliferation by liposome-plasmid DNA complex. Biochem. Biophys. Res. Commun. 207: 492–496.

    CrossRef  PubMed  CAS  Google Scholar 

  34. Nabel, E. G., Yang, Z. Y., Plautz, G., Forough, R., Zhan, X., Haudenschild, C. C., Maciag, T., Nabel, G. J. (1993) Recombinant fibroblast growth factor 1 promotes intimal hyperplasia and angiogenesis in arteries in vivo. Nature 362: 844–846.

    CAS  Google Scholar 

  35. Nabel, E. G., Plautz, G. and Nabel, G. J. (1992) Transduction of a foreign histocompatibility gene into the arterial wall induces vasculitis. Proc. Natl. Acad. Sci. USA 89: 5157–5161.

    CrossRef  PubMed  CAS  Google Scholar 

  36. Schmid, R. M., Weidenbach, H., Draenert, G. E, Lerch, M. M., Liptay, S., Schorr, J., Beckh, K. H. and Adler, G. (1994) Liposome-mediated in vivo gene-transfer into different tissues of the gastrointestinal tract. Z. Gastroenterol. 32: 665–670.

    PubMed  CAS  Google Scholar 

  37. Leibiger, B., Leibiger, B., Sarrach, D., Zuhlke, H. (1991) Expression of exogenous DNA in rat liver cells after liposome mediated transfection in vivo. Biochem. Biophys. Res. Commun. 174: 1223–1231.

    CrossRef  CAS  Google Scholar 

  38. Watanabe, Y., Nomoto, H., Takezawa, R., Miyoshi, N., Akaike, T. (1994) Higly efficient transfection into primary cultured mouse hepatocytes by use of cation-liposomes: An application for immunization. J. Biochem. 116: 1220–1226.

    PubMed  CAS  Google Scholar 

  39. Lappalainen, K., Urtti, A., Jaaskelainen, I., Syrjanen, K. (1994) Cationic liposomes mediated delivery of antisense oligonucleotides targeted to HPV 16 E7 messenger RNA in Caski cells. Antivir. Res. 23: 119–130.

    CrossRef  PubMed  CAS  Google Scholar 

  40. Thierry, A. R., Dritschilo, A. (1992) Intracellular availability of unmodified, phosphorothioated and liposomally encapsulated oligodeoxynucleotides for antisense activity. Nucl. Acid. Res. 20: 5691–5698.

    CrossRef  CAS  Google Scholar 

  41. Zelphati, O., Imbach, J. L., Signoret, N., Zon, G., Rayner, B., Leserman, L. (1994) Antisense oligonucleotides in solution or encapsulated in immunoliposomes inhibit replication of HIV-1 by several different mechanisms. Nucl. Acid. Res. 22: 4307–4314.

    CrossRef  CAS  Google Scholar 

  42. Zelphati, O., Wagner, E. and Leserman, L. (1994) Synthesis and anti-HIV activity of thiocholesteryl-coupled phosphodiester antisense oligonucleotides incorporated into immunoliposomes. Antivir. Res. 25: 13–25.

    CrossRef  PubMed  CAS  Google Scholar 

  43. Harvie, P., Desormeaux, A., Gagne, N., Tremblay, M., Poulin, L., Beauchamp, D. and Bergeron, M. G. (1995) Lymphoid tissues targeting of liposome-encapsulated 2’,3’dideoxyinosine. AIDS 9: 701–707.

    CrossRef  PubMed  CAS  Google Scholar 

  44. Lu, D., Benjamin, R., Kim, M., Conry RM, and Curiel DT (1994) Optimization of methods to achieve mRNA-mediated transfection of tumor cells in vitro and in vivo employing cationic liposome vectors. Cancer Gene Ther. 1: 245–252.

    CAS  Google Scholar 

  45. Puyal, C., Milhaud, P., Bienvenue, A., Philippot, J. R. (1995) A new cationic liposome encapsulating genetic material: A potential delivery system for polynucleotides. Eur. J. Biochem. 228: 697–703.

    CrossRef  PubMed  CAS  Google Scholar 

  46. Zhou, X. H., Huang, L. (1994) DNA transfection mediated by cationic liposomes containing lipopolylysine-characterization and mechanism of action. Biochim. Biophys. Acta-Biomembranes 1189: 195–203.

    CrossRef  CAS  Google Scholar 

  47. Kaneda, Y., Iwai, K., Uchida, T. (1989) Increased expression of DNA co-introduced with nuclear protein in adult rat liver. Science 243: 375–378.

    CrossRef  PubMed  CAS  Google Scholar 

  48. Morishita, R., Gibbons, G. H., Ellison, K. E., Nakajima, M., Zhang, L., Kaneda, Y., Ogiara, T., Dzau, V. J. (1993) Single intraluminal delivery of antisense CDC2 kinase and proliferating cell nuclear antigen oligonucleotides results in chronic inhibition of neointimal hyperplasia. Proc. Natl. Acad. Sci. USA 90: 8474–8478.

    CrossRef  PubMed  CAS  Google Scholar 

  49. Tomita, N., Higaki, J., Ogihara, T., Kondo, T., Kaneda, Y. (1994) A novel gene-transfer technique mediated by HVJ (Sendai virus), nuclear protein and liposomes. Cancer Detect. Prevent. 18: 485–491.

    PubMed  CAS  Google Scholar 

  50. Kato, K., Nakanishi, M., Kaneda, Y., Uchida, T., Okada, Y. (1991) Expression of hepatitis B virus surface antigen in adult rat liver: co-introduction of DNA and nuclear protein by a simplified liposome method. J. Biol. Chem. 266: 3361–3364.

    PubMed  CAS  Google Scholar 

  51. Wang, C. Y. and Huang, L. (1987) pH-sensitive immunoliposomes mediate target-cellspecific delivery and controlled expression of a foreign gene in mouse. Proc. Natl. Acad. Sci. USA 84: 7851–5.

    Google Scholar 

  52. Connor, J. and Huang, L. (1985) Efficient cytoplasmic delivery of a fluorescent dye by pH-sensitive immunoliposomes. J. Cell Biol. 101: 582.

    CrossRef  PubMed  CAS  Google Scholar 

  53. Brown, P. M. and Silvius, J. R. (1990) Mechanism of delivery of liposome-encapsulated cytosine arainoside to CV-1 cells in vitro. Fluorescence-microscopic and cytotoxicity studies. Biochim. Biophys. Acta 1023: 341–351.

    CrossRef  PubMed  CAS  Google Scholar 

  54. Collins, D. and Huang L. (1987) Cytotoxicity of diphteria toxin A fragment to toxin-resistant murine cells delivered by pH-sensitive immunoliposomes. Cancer Res. 47: 735739.

    Google Scholar 

  55. Collins, D., Litzinger, D. and Huang, L. (1990) Structural and functional comparisons of pH-sensitive liposomes composed of phosphatidylethanolamine and three different diacylsuccinylglycerols. Biochim. Biophys. Acta 1025: 234–242.

    CrossRef  PubMed  CAS  Google Scholar 

  56. Collins, D., Maxfield, F. R. and Huang, L. (1989) Immunoliposomes with different acid sensitivities as probes for the cellular endocytic pathway. Biochim. Biophys. Acta 987: 47–55.

    CrossRef  PubMed  CAS  Google Scholar 

Download references

Authors
  1. O. Bagasra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Amjad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Mukhtar
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Max-Delbrück-Centrum für molekulare Medizin, Robert-Rössle-Strasse 10, D-13122, Berlin-Buch, Germany

    Prof. Dr. Thomas Blankenstein

Rights and permissions

Reprints and Permissions

Copyright information

© 1999 Birkhäuser Verlag Basel

About this chapter

Cite this chapter

Bagasra, O., Amjad, M., Mukhtar, M. (1999). Liposomes in Gene Therapy. In: Blankenstein, T. (eds) Gene Therapy. Birkhäuser Basel. https://doi.org/10.1007/978-3-0348-7011-5_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-7011-5_5

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-0348-7013-9

  • Online ISBN: 978-3-0348-7011-5

  • eBook Packages: Springer Book Archive