Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Minimally invasive and selective hydrodynamic gene therapy of liver segments in the pig and human

Cancer Gene Therapy volume 15, pages 225–230 (2008)Cite this article

Abstract

This paper highlights our experience of the transfer of hydrodynamic gene therapy (HGT) from the large animal, the pig, into clinical practice. The modification of balloon catheters and the development of a minimally invasive technique to allow selective isolation of liver segments for HGT in the large animal and human are described. Finally, our preliminary results from a phase I clinical study of HGT for thrombopoietin (TPO) in cirrhotic patients with thrombocytopenia are discussed. Based on these provisional data, minimally invasive selective HGT of liver segments appears to be technically safe, but further work is required to optimize the efficiency of gene transfer in order to achieve clinical benefit.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  1. Budker V, Zhang G, Knechtel S, Wolff JA . Naked DNA delivered intraportally expresses efficiently in hepatocytes. Gene Therapy 1996; 13: 593–598.

    Google Scholar 

  2. Liu F, Song YK, Liu D . Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA. Gene Therapy 1999; 6: 1258–1266.

    Article  CAS  Google Scholar 

  3. Zhang G, Gao X, Song YK, Vollmer R, Stolz DB, Gasiorowski JZ et al. Hydroboration as the mechanism of hydrodynamic delivery. Gene Therapy 2004; 11: 675–682.

    Article  CAS  Google Scholar 

  4. Kobayashi N, Nishikawa M, Hirata K, Takakura Y . Hydrodynamics-based procedure involves transient hyperpermeability in the hepatic cellular membrane: implication of a nonspecific process in efficient intracellular gene delivery. J Gene Med 2004; 6: 584–592.

    Article  CAS  Google Scholar 

  5. Andrianaivo F, Lecocq M, Wattiaux-De Coninck S, Wattiaux R, Jadot M . Hydrodynamics-based transfection of the liver: entrance into hepatocytes of DNA that causes expression takes place very early after injection. J Gene Med 2004; 6: 877–883.

    Article  CAS  Google Scholar 

  6. Crespo A, Peydro A, Dasi F, Benet M, Calvete JJ, Revert F, Alino SF . Hydrodynamic liver gene transfer mechanism involves transient sinusoidal blood stasis and massive hepatocyte endocytic vesicles. Gene Therapy 2005; 12: 927–937.

    Article  CAS  Google Scholar 

  7. Miao CH, Thompson AR, Loeb K, Ye X . Long term transgene and therapeutic level hepatic gene expression of human factor IX after naked plasmid transfer in vivo. Mol Ther 2001; 3: 947–957.

    Article  CAS  Google Scholar 

  8. Eastman SJ, Baskin KM, Hodges BL, Chu O, Gates A, Dreusike R et al. Development of catheter-based procedures for transducing the isolated rabbit liver with plasmid DNA. Hum Gene Ther 2002; 13: 2065–2077.

    Article  CAS  Google Scholar 

  9. Alino SF, Herrero MF, Noguera I, Dasi F, Sanchez M . Pig liver gene therapy by noninvasive interventionist catheterism. Gene Therapy 2007; 14: 334–343.

    Article  CAS  Google Scholar 

  10. Yoshino H, Hashizume K, Kobayashi E . Naked plasmid DNA transfer to the porcine liver using rapid injection with large volume. Gene Therapy 2006; 13: 1696–1702.

    Article  CAS  Google Scholar 

  11. Habib N, Havlik R, Jiao L, Kiri A, Jensen S, Nicholls J et al. Combination of Optison™ with ultrasound and electroporation increases albumin and thrombopoietin transgene expression whilst elongation factor promoter prolongs its duration. Gene Ther Mol Biol 2004; 8: 1–7.

    Google Scholar 

Download references

Acknowledgements

This work was generously supported by the Pedersen Family Charitable Foundation and InvivoGen Inc.

Author information

Authors and Affiliations

  1. Faculty of Medicine, Imperial College London, London, UK

    S E Khorsandi, P Bachellier, J C Weber, S Helmy, L Jiao, J Nicholls, A J Davies, N Levicar, S Jensen & N Habib

  2. Foundation Transplantation, Strasbourg, Hôspital Hautpierre, Strasbourg, France

    P Bachellier, J C Weber, M Greget & D Jaeck

  3. Larissa University School of Medicine, Larissa, Greece

    D Zacharoulis & C Rountas

  4. Faculty of Medicine, Cairo University, Cairo, Egypt

    S Helmy, A Helmy, M Al-Waracky & H Salama

Authors
  1. S E Khorsandi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P Bachellier
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J C Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Greget
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D Jaeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D Zacharoulis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C Rountas
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S Helmy
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A Helmy
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M Al-Waracky
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. H Salama
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. L Jiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. J Nicholls
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. A J Davies
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. N Levicar
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. S Jensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. N Habib
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N Habib.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khorsandi, S., Bachellier, P., Weber, J. et al. Minimally invasive and selective hydrodynamic gene therapy of liver segments in the pig and human. Cancer Gene Ther 15, 225–230 (2008). https://doi.org/10.1038/sj.cgt.7701119

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.cgt.7701119

Keywords

This article is cited by

Search

Advanced search

Quick links