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.

  • Brief Communication
  • Published:

Erythrocyte ghost-mediated gene delivery for prolonged and blood-targeted expression

Gene Therapy volume 11, pages 492–496 (2004)Cite this article

Abstract

This study reports the use of erythrocyte ghosts (EG) as a biocompatible nonviral delivery system for extended circulation and prolonged expression of plasmid DNA in the blood. Murine interleukin-2-expressing plasmid DNA was efficiently loaded to EG by electroporation in hypotonic condition. The presence of plasmid DNA in EG was confirmed by fluorescence-labeled plasmid DNA. At 21 min after intravenous administration into mice, the level of plasmid DNA in the blood was 92 000-fold higher following EG-mediated delivery as compared to the injection of naked form. EG-mediated gene delivery revealed higher and more prolonged mRNA expression levels of plasmid DNA in the blood until 9 days after the single intravenous injection. Moreover, plasmid DNA-loaded EG showed gene expression targeted to the blood cells. At 3 days post-dose, substantial expression levels of plasmid DNA delivered in EG were observed only in the blood and not in the other organs. Of the blood cells, the subpopulation containing granulocytes showed higher expression of plasmid DNA than mononuclear cells. These results indicate the potential of EG as a safe, prolonged and blood-targeted delivery system of therapeutic genes.

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

Similar content being viewed by others

References

  1. Fenske DB, Maclachlan I, Cullis PR . Long-circulating vectors for the systemic delivery of genes. Curr Opin Mol Ther 2001; 3: 153–158.

    CAS  PubMed  Google Scholar 

  2. Oh YK et al. Prolonged organ retention and safety of plasmid DNA administered in polyethylenimine complexes. Gene Therapy 2001; 8: 1587–1592.

    Article  CAS  Google Scholar 

  3. Ward CM, Read ML, Seymour LW . Systemic circulation of poly(L-lysine)/DNA vectors is influenced by polycation molecular weight and type of DNA: differential circulation in mice and rats and the implications for human gene therapy. Blood 2001; 97: 2221–2229.

    Article  CAS  Google Scholar 

  4. Oupicky D, Ogris M, Howard KA, Dash PR . Importance of lateral and steric stabilization of polyelectrolyte gene delivery vectors for extended systemic circulation. Mol Ther 2002; 5: 463–472.

    Article  CAS  Google Scholar 

  5. Tam P et al. Stabilized plasmid-lipid particles for systemic gene therapy. Gene Therapy 2000; 7: 1867–1874.

    Article  CAS  Google Scholar 

  6. Ogris M et al. PEGylated DNA/transferrin–PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Therapy 1999; 6: 595–605.

    Article  CAS  Google Scholar 

  7. Tan Y et al. Sequential injection of cationic liposome and plasmid DNA effectively transfects the lung with minimal inflammatory toxicity. Mol Ther 2001; 3: 673–682.

    Article  CAS  Google Scholar 

  8. Rossi L et al. Erythrocyte-mediated delivery of a new homodinucleotide active against human immunodeficiency virus and herpes simplex virus. J Antimicrob Chemother 2001; 47: 819–827.

    Article  CAS  Google Scholar 

  9. Magnani M et al. Erythrocyte-mediated delivery of drugs, peptides and modified oligonucleotides. Gene Therapy 2002; 9: 749–751.

    Article  CAS  Google Scholar 

  10. Bax BE et al. In vitro and in vivo studies with human carrier erythrocytes loaded with polyethylene glycol-conjugated and native adenosine deaminase. Br J Haematol 2000; 109: 549–554.

    Article  CAS  Google Scholar 

  11. Lizano C, Perez MT, Pinilla M . Mouse erythrocytes as carriers for coencapsulated alcohol and aldehyde dehydrogenase obtained by electroporation in vivo survival rate in circulation, organ distribution and ethanol degradation. Life Sci 2001; 68: 2001–2016.

    Article  CAS  Google Scholar 

  12. Bax BE et al. Survival of human carrier erythrocytes in vivo. Clin Sci 1999; 96: 171–178.

    Article  CAS  Google Scholar 

  13. Oh YK et al. Polyethylenimine-mediated cellular uptake, nucleus trafficking and expression of cytokine plasmid DNA. Gene Therapy 2002; 9: 1627–1632.

    Article  CAS  Google Scholar 

  14. Kruse CA, Mierau GW, James GT . Methotrexate loading of red cell carriers by osmotic stress and electric-pulse methods: ultrastructural observations. Biotechnol Appl Biochem 1989; 11: 571–580.

    CAS  PubMed  Google Scholar 

  15. Haritou M, Yova D, Koutsouris D, Loukas S . Loading of intact rabbit erythrocytes with fluorophores and the enzyme pronase by means of electroporation. Clin Hemorheol Microcirc 1998; 19: 205–217.

    CAS  PubMed  Google Scholar 

  16. Li LH, Hensen ML, Zhao YL, Hui SW . Electrofusion between heterogeneous-sized mammalian cells in a pellet: potential applications in drug delivery and hybridoma formation. Biophys J 1996; 71: 479–486.

    Article  CAS  Google Scholar 

  17. Simon SI, Goldsmith HL . Leukocyte adhesion dynamics in shear flow. Ann Biomed Eng 2002; 30: 315–332.

    Article  Google Scholar 

  18. Oh YK, Swanson JA . Different fates of phagocytosed particles following delivery into macrophage lysosomes. J Cell Biol 1996; 132: 585–593.

    Article  CAS  Google Scholar 

  19. Oh YK et al. Nasal absorption and biodistribution of plasmid DNA: an alternative route of DNA vaccine delivery. Vaccine 2001; 19: 4519–4525.

    Article  CAS  Google Scholar 

  20. Jung HC, Kim JM, Song IS, Kim CY . Helicobacter pylori induces an array of pro-inflammatory cytokines in human gastric epithelial cells: quantification of mRNA for interleukin-8, -1α/β, granulocyte–macrophage colony-stimulating factor, monocyte chemoattractant protein-1 and tumour necrosis factor-α. J Gastroenterol Hepatol 1997; 12: 473–480.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant of the Korea Health 2001 R&D Project, Ministry of Health & Welfare, Republic of Korea (01-PJ1-PG3-21500-0008). We greatly appreciate Dr Young-Chul Sung (Pohang University of Science and Technology, Pohang, South Korea) for providing the murine IL-2 gene, pCIneoIL-2.

Author information

Authors and Affiliations

  1. College of Medicine and Research Institute of Basic Medical Science, Pochon CHA University, Kyonggi-do, South Korea

    H-M Byun, D Suh, H Yoon, JJ Ko & Y-K Oh

  2. College of Medicine and Institute of Biomedical Research, Hanyang University, Seoul, South Korea

    JM Kim

  3. College of Pharmacy, Yeungnam University, Kyungbuk, South Korea

    H-G Choi

  4. College of Medicine, Ewha Women's University, Seoul, South Korea

    W-K Kim

Authors
  1. H-M Byun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D Suh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. JM Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H-G Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. W-K Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. JJ Ko
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Y-K Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Byun, HM., Suh, D., Yoon, H. et al. Erythrocyte ghost-mediated gene delivery for prolonged and blood-targeted expression. Gene Ther 11, 492–496 (2004). https://doi.org/10.1038/sj.gt.3302180

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gt.3302180

Keywords

This article is cited by

Search

Advanced search

Quick links