Journal of Korean Endocrine Society 2000;15(2):262-271.
Published online January 1, 2001.
IL-10 Plasmid DNA Delivery in NOD Mice for the Prevention of Autoimmune Pancreatic Beta Cell Destruction.
Jae Joon Koh, Kyung Soo Ko, Jong Sang Park, Won Bae Kim, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee, San Goo Shin, Sung Wan Kim
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.
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.
Key Words: mIL-10(mouse interleukin-10), PAGA(poly[-(4-aminobutyl)-L-glycolic acid]), NOD (non-obese diabetic) mice, Gene therapy, Non-viral gene delivery
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