J Korean Soc Endocrinol.
2000 Jun;15(2):262-271.
IL-10 Plasmid DNA Delivery in NOD Mice for the Prevention of Autoimmune Pancreatic Beta Cell Destruction
- Affiliations
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- 1Department of Internal Medicine, Boramae Hospital, Korea.
- 2Department of Internal Medicine, College of Medicine, Inje University, Korea.
- 3Department of Chemistry, College of Medicine, Seoul National University, Seoul, Korea.
- 4Department of Internal Medicine, College of Medicine, Seoul National University, Seoul, Korea.
- 5Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea.
- 6Department of pharmaceutics and pharmaceutical chemistry, Center for Controlled Chemical Delivery, University of Utah, Salt Lake City, UT, USA.
Abstract
- BACKGROUND
Recently, we have reported that biodegradable poly [-(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.
METHODS
PAGA/mIL-10 plasmid complexes were stable for more than 60 minutes, but the naked DNA was destroyed within 10 minutes by DNase I. The PAGA/DNA complexes were injected into the tail vein of 3 week-old NOD mice.
RESULTS
Serum mIL-10 level peaked at 5 days after injection, could be detected for more than 7 weeks. The prevalence of severe insulitis at 12 week-old NOD mice was markedly reduced by the intravenous injection of PAGA/DNA complex (15.7%) compared to 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.
CONCLUSION
The study presents the PAGA/DNA complex has the potential for the application of the prevention of autoimmune diabetes mellitus.
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