Skip to main content

Thank you for visiting 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.

Degradable polymeric carrier for the delivery of IL-10 plasmid DNA to prevent autoimmune insulitis of NOD mice


Recently, we have reported that biodegradable poly [α-(4-aminobutyl)-L-glycolic acid] (PAGA) can condense and protect plasmid DNA from DNase I. In this study, we investigated whether the systemic administration of pCAGGS mouse IL-10 (mIL-10) expression plasmid complexed with PAGA can reduce the development of insulitis in non-obese diabetic (NOD) mice. PAGA/mIL-10 plasmid complexes were stable for more than 60 min, but the naked DNA was destroyed within 10 min by DNase I. The PAGA/DNA complexes were injected into the tail vein of 3-week-old NOD mice. Serum mIL-10 level peaked at 5 days after injection, and could be detected for more than 9 weeks. The prevalence of severe insulitis on 12-week-old NOD mice was markedly reduced by the intravenous injection of PAGA/DNA complex (15.7%) compared with that of naked DNA injection (34.5%) and non-treated controls (90.9%). In conclusion, systemic administration of pCAGGS mIL-10 plasmid/PAGA complexes can reduce the severity of insulitis in NOD mice. This study shows that the PAGA/DNA complex has the potential for the prevention of autoimmune diabetes mellitus.

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

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6


  1. Nitta Y et al. Systemic delivery of interleukin 10 by intramuscular injection of expression plasmid DNA prevents autoimmune diabetes in nonobese diabetic mice Hum Gene Ther 1998 9: 1701–1707.

    Article  CAS  Google Scholar 

  2. Piccirillo CA, Chang Y, Prud'homme GJ . TGF-β1 somatic gene therapy prevents autoimmune disease in nonobese diabetic mice J Immunol 1998 161: 3950–3956

    CAS  PubMed  Google Scholar 

  3. Prud'homme GJ, Chang Y . Prevention of autoimmune diabetes by intramuscular gene therapy with a nonviral vector encoding an interferon-gamma receptor/IgG1 fusion protein Gene Therapy 1999 6: 771–777

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. Budker V et al. The efficient expression of intravascularly delivered DNA in rat muscle Gene Therapy 1998 5: 272–276

    Article  CAS  Google Scholar 

  6. Wolff J . Naked DNA gene transfer in mammalian cells. In: Friedman T (ed) The Development of Gene Therapy Cold Spring Harbor Laboratory Press: New York 1998 279–307

    Google Scholar 

  7. Yoshida M et al. Disposition characteristics of plasmid DNA in the single-pass rat liver perfusion system Pharm Res 1996 13: 599–603.

    Article  CAS  Google Scholar 

  8. Mahato RI et al. Biodistribution and gene expression of lipid/plasmid complexes after systemic administration Hum Gene Ther 1998 9: 2083–2099

    Article  CAS  Google Scholar 

  9. Lim Y et al. Biodegradable polyester, poly[α-(4-aminobutyl)-L-glycolic acid], as a non-toxic gene carrier Pharm Res 2000 17: 811–816.

    Article  CAS  Google Scholar 

  10. Li S, Huang L . In vivo gene transfer via intravenous administration of cationic lipid-protamine-DNA (LPD) complexes Gene Therapy 1997 4: 891–900

    Article  CAS  Google Scholar 

  11. Liu F, Qi H, Huang L, Liu D . Factors controlling the efficiency of cationic lipid-mediated transfection in vivo via intravenous administration Gene Therapy 1997 4: 517–523

    Article  CAS  Google Scholar 

  12. Zhang G, Budker V, Wolff JA . High levels of foreign gene expression in hepatocytes after tail vein injections of naked plasmid DNA Hum Gene Ther 1999 10: 1735–1737

    Article  CAS  Google Scholar 

  13. Gershon H, Ghirlando R, Guttman SB, Minsky A . Mode of formation and structural features of DNA–cationic liposome complexes used for transfection Biochemistry 1993 32: 7143–7151

    Article  CAS  Google Scholar 

  14. Kawabata K, Takakura Y, Hashida M . The fate of plasmid DNA after intravenous injection in mice: involvement of scavenger receptors in its hepatic uptake Pharm Res 1995 12: 825–830

    Article  CAS  Google Scholar 

  15. Wang J et al. Synthesis and characterization of long chain alkyl acyl carnitine esters. Potentially biodegradable cationic lipids for use in gene delivery J Med Chem 1998 41: 2207–2215

    Article  CAS  Google Scholar 

  16. Tang F, Hughes JA . Synthesis of a single-tailed cationic lipid and investigation of its transfection J Control Release 1999 62: 345–358.

    Article  CAS  Google Scholar 

  17. Zabner J et al. Cellular and molecular barriers to gene transfer by a cationic lipid J Biol Chem 1995 270: 18997–19007

    Article  CAS  Google Scholar 

  18. Xu Y, Szoka FC Jr . Mechanism of DNA release from cationic liposome/DNA complexes used in cell transfection Biochemistry 1996 35: 5616–5623

    Article  CAS  Google Scholar 

  19. Nicholson LB, Kuchroo VK . Manipulation of the Th1/Th2 balance in autoimmune disease Curr Opin Immunol 1996 8: 837–842.

    Article  CAS  Google Scholar 

  20. Rabinovitch A . Immunoregulatory and cytokine imbalances in the pathogenesis of IDDM. Therapeutic intervention by immunostimulation Diabetes 1994 43: 613–621

    Article  CAS  Google Scholar 

  21. Mosmann TR, Coffman RL . TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties Annu Rev Immunol 1989 7: 145–173

    Article  CAS  Google Scholar 

  22. Romagnani S . The Th1/Th2 paradigm Immunol Today 1997 18: 263–266

    Article  CAS  Google Scholar 

  23. Adorini L, Trembleau S . Immune deviation towards Th2 inhibits Th-1-mediated autoimmune diabetes Biochem Soc Trans 1997 25: 625–629.

    Article  CAS  Google Scholar 

  24. Rapoport MJ et al. Interleukin 4 reverses T cell proliferative unresponsiveness and prevents the onset of diabetes in nonobese diabetic mice J Exp Med 1993 178: 87–99

    Article  CAS  Google Scholar 

  25. Pennline KJ, Roque-Gaffney E, Monahan M . Recombinant human IL-10 prevents the onset of diabetes in the nonobese diabetic mouse Clin Immunol Immunopathol 1994 71: 169–175

    Article  CAS  Google Scholar 

  26. Hart SL et al. Gene delivery and expression mediated by an integrin-binding peptide Gene Therapy 1995 2: 552–554

    CAS  PubMed  Google Scholar 

  27. Vitiello L et al. Condensation of plasmid DNA with polylysine improves liposome-mediated gene transfer into established and primary muscle cells Gene Therapy 1996 3: 396–404

    CAS  PubMed  Google Scholar 

  28. Signore A et al. Histological study of pancreatic beta-cell loss in relation to the insulitis process in the non-obese diabetic mouse Histochemistry 1994 101: 263–269

    Article  CAS  Google Scholar 

Download references


The authors thank Expression Genetics Inc for financial support, and Jun-Ichi Miyazaki of Osaka University, Japan for generous gift of pCAGGS mIL-10 plasmid. We would like to thank Troy Koch for technical assistance.

Author information

Authors and Affiliations


Rights and permissions

Reprints and Permissions

About this article

Cite this article

Koh, J., Ko, K., Lee, M. et al. Degradable polymeric carrier for the delivery of IL-10 plasmid DNA to prevent autoimmune insulitis of NOD mice. Gene Ther 7, 2099–2104 (2000).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • gene therapy
  • insulitis
  • interleukin-10
  • NOD mouse
  • poly [α-(4-aminobutyl)-L-glycolic acid] (PAGA)

This article is cited by


Quick links