Skip to main content
SpringerLink
Log in

Methods for Targeted Gene Transfer to Liver Using DNA-Protein Complexes

  • Protocol
Gene Therapy Protocols

Part of the book series: Methods in Molecular Medicine ((MIMM,volume 7))

  • 611 Accesses

Abstract

The potential of therapeutic gene transfer to treat human disease has prompted a diverse and growing range of basic and applied research efforts to explore and develop gene therapy strategies (1-5). Reported approaches to gene therapy mclude the uses of retroviruses (6,7), adenovirus (8,9), receptor-mediated endocytosis (10,11), direct injection (12), and liposomes (13,14), among others. Targeted delivery of DNA via receptors has been successfully applied using protein ligands to the hepatic asialoglycoprotein receptor (ASGr) (10,15-18), and, subsequently, the transferrin receptor (11). The ASGr is a cell-surface receptor that is highly represented on hepatocytes. Thus, genes targeted to this receptor can be delivered in a highly selective manner to the liver.

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

Access this chapter

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 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Wolff, J. A. (ed.) (1994) Gene Therapeutics: Methods and Applications of Direct Gene Transfer, Birkhauser, Boston.

    Google Scholar 

  2. Findeis, M. A. (1994, April issue) Genes to the rescue, Technol Rev 97, 46–53.

    Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Anderson, W. F. (1992) Human gene therapy. Science 256, 808–813

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. Mulligan, R. C. (1991) Gene transfer and gene therapy: principles, prospects, and perspective, in Etiology of Human Disease at the DNA Level (Lindsten, J. and Pettersson, U., eds.), Raven, New York, pp. 143–189.

    Google Scholar 

  7. Jolly, D. J., Yee, J.-K., and Friedmann, T. (1987) High-effciency gene transfer into cells. Methods Enzymol 149, 10–25.

    Article  CAS  Google Scholar 

  8. Rosenfeld, M. A., Yoshimura, K., Trapnell, B. C., Yoneyama, K., Rosenthal, E. R., Dalemans, W., Fukayama, M., Bargon, J., Stier, L. E., Stratford-Perricaudet, L., Perricaudet, M., Guggino, W. B., Pavirani, A., Lecocq, J.-P., and Crystal, R G. (1992) In vivo transfer of the human cystic fibrosis transmembrane conductance regulator gene to the airway epithelium. Cell 68, 143–155.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  10. Wu, G. Y. and Wu, C. H. (1987) Receptor-mediated in vitro gene transformation by a soluble DNA carrier system. J Boil Chem 262, 4429–4432.

    Article  CAS  Google Scholar 

  11. Wagner, E., Zenke, M., Cotten, M., Beug, H., and Birnstiel, M L. (1990) Trans-ferrin-polycation conjugates as carriers for DNA uptake into cells Proc. Natl. Acad. sci. USA 87, 3410–3414.

    Article  CAS  Google Scholar 

  12. Nabel, G J. and Felgner, P. L. (1993) Direct gene transfer for immunotherapy and immunization. Trends Biotechnol. 11, 211–215.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  14. Stribling, R., Brunette, E., Liggitt, D., Gaensler, K., and Debs, R. (1992) Aerosol gene delivery in vivo. Proc. Natl. Acad. Sci USA 89, 11,277–11,281.

    Article  CAS  Google Scholar 

  15. Findeis, M. A, Merwin, J. R., Spitalny, G. L., and Chiou, H C. (1993) Targeted delivery of DNA for gene therapy via receptors. Trends Biotechnol 11, 202–205.

    Article  CAS  Google Scholar 

  16. Chiou, H. C., Spitalny, G. L., Merwin, J. R., and Findeis, M. A. (1994) In viva gene therapy via receptor-mediated DNA delivery, in Gene Therapeutics Methods and Applications of Dired Gene Transfer (Wolff, J. A., ed.), Birkhäuser, Boston, pp. 143–156.

    Google Scholar 

  17. Findeis, M A., Wu, C H.,and Wu, G.Y. (1994) Ligand-based carrier systems for delivery of DNA to hepatocytes, in Neoglycoconjugates, Methods in Enzymology (Lee, Y C., and Lee, R. T, eds.), pp. 341–350.

    Google Scholar 

  18. Wu, G. Y. and Wu, C. H. (1991) Targeted delivery and expression of foreign genes in hepatocytes, in Liver Diseases, Targeted Diagnosis and Therapy Using Specific Receptors and Ligands (Wu, G. Y. and Wu, C. H., eds), Marcel Dekker, New York, pp. 127–149.

    Google Scholar 

  19. Wu, G. Y., Wu, C. H., and Stocker, R. J. (1983) Model for specific rescue of normal hepatocytes during methotrexate treatment of hepatic malignancy. Proc. Natl Acad Sci. USA 80, 3078–3080.

    Article  CAS  Google Scholar 

  20. Wu, G. Y., Wu, C. H., and Rubin, M. I. (1985) Acetaminophen hepatotoxicity and targeted rescue: a model for specific chemotherapy of hepatocellular carcinoma. Hepatology 5, 709–713.

    Article  CAS  Google Scholar 

  21. Keegan-Rogers, V. and Wu, G. Y. (1990) Targeted protection of hepatocytes from galactosamine toxicity in vivo. Cancer Chemother. Pharmacol. 26, 93–96.

    Article  CAS  Google Scholar 

  22. Wu, G. Y., Keegan-Rogers, V., Franklin, S., Midford, S., and Wu, C. H. (1988) Targeted antagonism of galactosamine toxicity in normal rat hepatocytes in vitro J. Biol. Chem. 263, 4719–4723.

    Article  CAS  Google Scholar 

  23. Ponzetto, A., Fiume, L., Forzani, B., Song, S. H., Busi, C., Mattioli, A., Spinelli, C., Marinelli, M., Smedile, A., Chiaberge, E., Bonino, F., Gervasi, G. B., Rapicetta, M., and Verme, G. (1991) Adenine arabinoside monophosphate and acyclovir monophosphate coupled to lactosaminated albumin reduce woodchuck hepatitis virus viremia at lower doses than do the unconjugated drugs Hepatology 14, 16–24.

    Article  CAS  Google Scholar 

  24. Fiume, L., Busi, C., Mattioli, A., Balboni, P. G., and Barbanti-Brodano, G. (1981) Hepatocyte targeting of adenine-9-β-D-arabinofkranoside 5′-monophosphate (ara-AMP) coupled to lactosaminated albumin FEBS Lett. 129, 26l–264.

    Article  Google Scholar 

  25. Wu, G. Y. and Wu, C. H. (1987) Receptor-mediated in vitro gene transformation by a soluble DNA carrier system. J Biol Chem 262, 4429–4432.

    Article  CAS  Google Scholar 

  26. Wu, G Y and Wu, C H. (1992) Specific inhibition of hepatitis B viral gene expression in vitro by targeted antisense oligonucleotides. J Biol. Chem. 267, 12,436–12,439.

    Article  CAS  Google Scholar 

  27. Cristiano, R. J., Smith, L. C., and Woo, S. L. C. (1993) Hepatic gene therapy. adenovirus enhancement of receptor-mediated gene delivery and expression in primary heaptocytes Proc Natl Acad Sci USA 90, 2122–2126.

    Article  CAS  Google Scholar 

  28. Wu, G Y. and Wu, C. H. (1988) Receptor-mediated gene delivery and expression in vivo. J Biol Chem 263, 14,621–14,624.

    Article  CAS  Google Scholar 

  29. Wu, G. Y., Wilson, J. M., and Wu, C H. (1989) Targeting genes: delivery and persistent expression of a foreign gene driven by mammalian regulatory elements in vivo. J. Biol. Chem. 264, 16,985–16,987.

    Article  CAS  Google Scholar 

  30. 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.

    Article  CAS  Google Scholar 

  31. Wilson, J. M., Grossman, M., Cabrera, J. A., Wu, C. H., Chowdhury, N. R., Wu, G Y., and Chowdhury, J. R. (1992) Hepatocyte-directed gene transfer in vivo leads to transient improvement of hypercholesterolemia in low density lipopro-tein receptor-deficient rabbits. J Biol Chem 267, 963–967.

    Article  CAS  Google Scholar 

  32. Wilson, J M., Grossman, M., Cabrera, J. A., Wu, C. H., and Wu, G. Y (1992) A novel mechanism for achieving transgene persisitence in vivo after somatic gene transfer into hepatocytes. J. Biol. Chem. 267, 11,483–11,489.

    Article  CAS  Google Scholar 

  33. Wu, G. Y., Zhan, P. L., Sze, L. L., Rosenberg, A. R., and Wu, C. H. (1994) Incorporation of adenovirus into a ligand-based DNA carrier system results in retention of the original receptor specificity and enhances targeted gene expression. J. Biol. Chem. 269, 11,542–11,546.

    Article  CAS  Google Scholar 

  34. Huebner, R. J., Rowe, W. P., Ward, T. G., Parrott, R. H., and Bell, J. A. (1954) Adenoidal-pharyngeal-conjunctival agents: a newly recognized group of common viruses of the respiratory system. N. Engl J Med. 251, 1077–1086.

    Article  CAS  Google Scholar 

  35. Pereira, H. G., Huebner, R. J., Ginsberg, H. S., and Van der Veen, J. (1963) A short description of the adenovirus group. Virology 20, 613–620.

    Article  CAS  Google Scholar 

  36. Grayston, J. T., McCarthy, M. A., Smith, M., and Loosli, C. G (1958) Adenoviruses. II. The sensitivity of different tissue culture strains of cells to adenoviruses. J. Infect. Dis. 103, 86–92.

    Article  CAS  Google Scholar 

  37. Hennache, B. and Boulanger, P. (1977) Biochemical study of KB-cell receptor for adenovirus. Biochem. J. 166, 237–247.

    Article  CAS  Google Scholar 

  38. Chardonnet, Y. and Dales, S. (1970) Early events in the interaction of adenoviruses with HeLA cells. I. Penetration of type 5 and instracellular release of the DNA gnome. Virology 40, 462–477.

    Article  CAS  Google Scholar 

  39. 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.

    CAS  Google Scholar 

  40. 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.

    Article  CAS  Google Scholar 

  41. Ishibashi, M., and Maizel, J. V., Jr. (1974) The polypeptides of adenoviruses IV. Early and late glycopolypeptides. Virology 58, 345–361.

    Article  CAS  Google Scholar 

  42. Whitehead, P. H. and Sammons, H. G. (1966) A simple technique for the isolation of orosomucoid from normal and pathological sera. Biochim Biophys Acta 124, 209–211.

    Article  CAS  Google Scholar 

  43. Schmid, K., Polis, A., Hunziker, K., Fricke, R., and Yayoshi, M. (1967) Partial characterization of the stalic acid-free forms of al-acid glycoprotein from human plasma. Biochem. J. 104, 361–368.

    Article  CAS  Google Scholar 

  44. McKee, T. D., DeRome, M E., Wu, G. Y., and Findeis, M. A (1994) Preparation of asialoorosomucoid-polylysine conjugates for targeted delivery of DNA. Bioconjugate Chem 5, 306–311.

    Article  CAS  Google Scholar 

  45. Sambrook, J, Fritsch, E F., and Maniatis, T (1989) Molecular Cloning, 2nd ed, Cold Spring Harbor Laboratory, Cold Spring Harbor, Chapter 6, pp. 6.2–6 13

    Google Scholar 

  46. Hames, B. D (1981) An introduction to polyacrylamide gel electrophoresis, in Gel Electrophoresis of Proteins (Hames, B. D. and Rickwood, D, eds.), IRL, Oxford, UK, Chapter 1.

    Google Scholar 

  47. Schmid, K. (1976) α1Acid glycoprotein, in The Plasma Proteins, 2nd ed., vol. 1. (Putnam, F. W., ed.), Academic, New York, pp. 183–228.

    Google Scholar 

  48. Schmid, K. (1989) Human plasma α1-acid glycoprotein-biochemical properties, the amino acid sequence and the structure of the carbohydrate moiety, variants and polymorphism, in Alpha I-Acid Glycoprotein Genetics, Biochemistry, Physiological Functions, and Pharmacology, Progress In Clinical and Biological Research, vol. 300 (Baumann, P., Eap, C. B., Muller, W. E., and Tillement, J.-P., eds.), Liss, New York, pp. 7–22.

    Google Scholar 

  49. Chait, B. T. and Kent, S. B. H. (1992) Weighing naked proteins: practical, high accuracy mass measurement of peptides and proteins Science 257, 1885–1894.

    Article  CAS  Google Scholar 

  50. Warren, L. (1959) The thiobarbituric acid assay of sialic acids. J. Biol. Chem 234, 1971–1975.

    Article  CAS  Google Scholar 

  51. Uchida, Y., Tsukuda, Y., and Sugimori, T. (1977) Distribution of neuraminidase in Arthrobacter and its purilication by affinity chromatography. J. Biochem. 82, 1425–1433.

    Article  CAS  Google Scholar 

  52. Panyim, S. and Chalkley, R. (1969) High resolution acrylamide gel electrophoresis of histones. Arch Biochem Biophys 130, 337–346.

    Article  CAS  Google Scholar 

  53. Green, M. and Piña, M. (1963) Biochemical studies on adenovirus multiplication. IV Isolation, purification,and chemical analysis of adenovirus Virology 20, 199–207.

    Article  CAS  Google Scholar 

  54. Jones, N. and Schenk, T. (1979) An adenovirus type 5 early gene function regulates expression of other early viral genes. Proc. Natl Acad sci USA 76, 3665–3669.

    Article  CAS  Google Scholar 

  55. Greenwood, F., Hunter, C. W. M., and Glover, J. S. (1963) The preparation of 131I-labelled human growth hormone of high specific radioactivity. Biochem J. 89, 114–123.

    Article  CAS  Google Scholar 

  56. Lawrence, W C., and Ginsburg, H. S. (1967) Intracellular uncoating of type 5 adenovirus deoxyribonucleic acid. J. Virology 1, 851–867.

    Article  CAS  Google Scholar 

  57. Precious, B., and Russell, W. C (1985) Growth, purification, and titration of adenoviruses, in Virology A Practical Approach (Mahy, B. W. J., ed.), IRL, Oxford, UK, pp. 193–205.

    Google Scholar 

  58. Rowe, D. W., Moen, R. C., Davidson, J. M., Byers, P. H, Bornstein, P., and Palmiter, R. D. (1978) Correlation of procollagen mRNA levels in normal and transformed chick embryo fibroblasts with different rates of procollagen synthesis. Biochemistry 17, 1581–1590.

    Article  CAS  Google Scholar 

  59. Liang, T. J., Makdisi, W. J., Sun, S., Hasegawa, K., Zhang, Y., Wands, J. R., Wu, C H., and Wu, G. Y (1993) Targeted transfection and expression of hepatitis B viral DNA in human hepatoma cells. J Clin Invest. 91, 1241–1246.

    Article  CAS  Google Scholar 

  60. Birnboim, H. C and Daly, J. (1979) A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res 7, 1513–1518.

    Article  CAS  Google Scholar 

  61. Bonnerot, C., Rocancourt, D., Briand, P., Grimber, G., and Nicolas, J.-F. (1987) A β-galactosidase hybrid protein targeted to nuclei as a marker for developmental studies. Proc. Natl. Acad. Sci. USA 84, 6795–6799.

    Article  CAS  Google Scholar 

  62. Beddington, R. S. P., Morgernsterm, J, Land, H., and Hogan, A (1989) In situ transgenic enzyme marker for the midgestational mouse embryo and the visualization of inner cell mass clones during early organogenesis. Development 106, 37–46.

    Article  CAS  Google Scholar 

  63. Sanes, J. R, Rubenstein, J. L. R., and Nicolas, J F (1986) Use of recombinant retrovirus to study post-implantation cell lineage in mouse embryos. EMBOJ, 5, 3133–3142.

    Article  CAS  Google Scholar 

  64. Carmichael, E. P., Chiou, H. C., Findeis, M. A., Spitalny, G. L., and Merwin, J R. (1995) Targeted delivery of anti-hepatitis B antisense oligonucleotides, in Delivery Systems for Antisense Oligonucleotide Therapeutics (Akhtar, S., ed.), CRC, Boca Raton, FL, pp 267–282.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharmaceutical Peptides, Inc., Cambridge, MA, USA

    Mark A. Findeis

  2. Division of Gastroenterology, University of Connecticut Health Center, Farmington, CT, USA

    Catherine H. Wu & George Y. Wu

Authors
  1. Mark A. Findeis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Catherine H. Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. George Y. Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Pittsburgh, PA, USA

    Paul D. Robbins

Rights and permissions

Reprints and permissions

Copyright information

© 1997 Humana Press Inc., Totowa, NJ

About this protocol

Cite this protocol

Findeis, M.A., Wu, C.H., Wu, G.Y. (1997). Methods for Targeted Gene Transfer to Liver Using DNA-Protein Complexes. In: Robbins, P.D. (eds) Gene Therapy Protocols. Methods in Molecular Medicine, vol 7. Humana, Totowa, NJ. https://doi.org/10.1385/0-89603-484-4:135

Download citation

  • DOI: https://doi.org/10.1385/0-89603-484-4:135

  • Publisher Name: Humana, Totowa, NJ

  • Print ISBN: 978-0-89603-484-6

  • Online ISBN: 978-1-59259-591-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation