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.

  • Research Article
  • Published:

Session V – DNA Transfer Vehicles

Erythrocyte-mediated delivery of drugs, peptides and modified oligonucleotides

Abstract

An important determinant for the success of every new therapy is the ability to deliver the molecules of interest to the target cells or organ. This selective delivery is even more complex when the therapeutic agents are peptides, modified oligonucleotides or genes. In this paper we summarize the possibility of using autologous erythrocytes for the delivery and targeting of new and conventional therapeutics. In fact, a number of macromolecules can be encapsulated by different procedures into human erythrocytes. These modified cells can then be re-infused into the same or a compatible recipient where they can circulate for several weeks. However, drug-loaded erythrocytes can also be modified to be selectively recognized by tissue macrophages. These phagocyte cells recognize the modified drug-loaded erythrocytes which are able to release their content into the macrophage. The feasibility and safety of the use of erythrocytes as drug delivery systems was evaluated in 10 cystic fibrosis patients, where a sustained release of corticosteroids from dexamethasone 21-phosphate-loaded erythrocytes was obtained. In vitro human erythrocytes were found to be able to deliver ubiquitin analogues and modified oligonucleotides to macrophages. Thus, drug-loaded erythrocytes are safe and useful carriers of new and conventional therapeutics and can be advantageous delivery systems for new clinical applications where proteins and oligonucleotides are therapeutic agents.

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

Access options

Buy this article

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

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Barker SA, Khossravi D . Drug delivery strategies for the new millenium Drug Discov Today 2001 6: 75–77

    Article  Google Scholar 

  2. Flott TR . Recombinant adeno-associated virus vectors for cystic fibrosis gene therapy Curr Opin Mol Ther 2001 3: 497–502

    Google Scholar 

  3. Cui FD et al. Highly efficient gene transfer into murine liver achieved by intravenous administraton of naked Epstein–Barr virus (EBV)-based plasmid vectors Gene Therapy 2001 8: 1508–1513

    Article  CAS  Google Scholar 

  4. Jayan GC et al. SV-40-derived vectors provide effective transgene expression and inhbition HIV-using constitutive, conditional, and pol III promotors Gene Therapy 2001 8: 1033–1042

    Article  CAS  Google Scholar 

  5. Klimatcheva E et al. Defective lentiviral vectors are efficiently trafficked by HIV-1 and inhibitor replication Mol Ther 2001 3: 928–939

    Article  CAS  Google Scholar 

  6. Schwartz JJ, Zhang S . Peptide-mediated cellular delivery Curr Opin Mol Ther 2000 2: 162–167

    CAS  PubMed  Google Scholar 

  7. Juliano RL, Yoo H . Aspects of the transport and delivery of antisense oligonucleotides Curr Opin Mol Ther 2000 2: 297–303

    CAS  PubMed  Google Scholar 

  8. Vyas SP, Singh A, Sihorkar V . Ligand-receptor-mediated drug delivery: an emerging paradigm in cellular drug targeting Crit Rev Ther Drug Carrier Syst 2001 18: 1–76

    Article  CAS  Google Scholar 

  9. Russell-Jones GJ . Use of vitamin B12 conjugates to deliver protein drugs by the oral route Crit Rev Ther Drug Carrier Sys 1998 15: 557–586

    CAS  Google Scholar 

  10. Reddy JA, Low PS . Folate-mediated targeting of theraputic and imaging agents to cancer Crit Rev Ther Drug Carrier Sys 1998 15: 587–627

    CAS  Google Scholar 

  11. Becker A et al. Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands Nature Biotech 2001 19: 327–331

    Article  CAS  Google Scholar 

  12. Magnani M et al. Erythrocyte engineering for drug delivery and targeting Biotechnol Appl Biochem 1998 28: 1–6

    CAS  PubMed  Google Scholar 

  13. Rossi L et al. Erythrocyte-mediated delivery of dexamethasone in patients with chronic obstructive pulmonary disease Biotech Appl Biochem 2001 33: 85–89

    Article  CAS  Google Scholar 

  14. Magnani M et al. Targeting antiretroviral nucleoside analogues in phosphorylated form to macrophages: in vitro and in vivo studies Proc Natl Acad Sci USA 1992 89: 6477–6481

    Article  CAS  Google Scholar 

  15. Chiarantini L, Rossi L, Fraternale A, Magnani M . Modulated red blood cell survival by membrane protein clustering Mol Cell Biochem 1995 144: 53–59

    Article  CAS  Google Scholar 

  16. Franchetti P et al. A new acyclic heterodinucleotide active against human immunodeficienct virus and herpes simplex virus Antivir Res 2000 47: 149–158

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  18. Magnani M et al. Targeting antiviral nucleotide analogues to macrophages J Leukocyte Biol 1997 62: 133–137

    Article  CAS  Google Scholar 

  19. Antonelli A et al. Efficient inhibition of macrophage TNF-α production upon targeted delivery of K48R ubiquitin Br J Haematol 1999 104: 475–481

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was partially supported by Project AIDS 1999, PRIN Project and Target Project on Biotechnology of CNR. We are indebted to Dr Massimo Castro, Vincenzina Lucidi and Francesco D'Orio from Hospital ‘Bambin Gesù’ in Rome for the studies on CF patients.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M Magnani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Magnani, M., Rossi, L., Fraternale, A. et al. Erythrocyte-mediated delivery of drugs, peptides and modified oligonucleotides. Gene Ther 9, 749–751 (2002). https://doi.org/10.1038/sj.gt.3301758

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gt.3301758

Keywords

This article is cited by

Search

Quick links