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J Korean Soc Endocrinol. 2000 Jun;15(2):262-271. Korean. Original Article.
Koh JJ , Ko KS , Park JS , Kim WB , Park KS , Kim SY , Lee HK , Shin SG , Kim SW .
Department of Internal Medicine, Boramae Hospital, Korea.
Department of Internal Medicine, College of Medicine, Inje University, Korea.
Department of Chemistry, College of Medicine, Seoul National University, Seoul, Korea.
Department of Internal Medicine, College of Medicine, Seoul National University, Seoul, Korea.
Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea.
Department 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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