IL-10 Plasmid DNA Delivery in NOD Mice for the Prevention of Autoimmune Pancreatic Beta Cell Destruction.
- Author:
Jae Joon KOH
1
;
Kyung Soo KO
;
Jong Sang PARK
;
Won Bae KIM
;
Kyong Soo PARK
;
Seong Yeon KIM
;
Hong Kyu LEE
;
San Goo SHIN
;
Sung Wan KIM
Author Information
1. Department of Internal Medicine, Boramae Hospital, Korea.
- Publication Type:Original Article
- Keywords:
mIL-10(mouse interleukin-10);
PAGA(poly[-(4-aminobutyl)-L-glycolic acid]);
NOD (non-obese diabetic) mice;
Gene therapy;
Non-viral gene delivery
- MeSH:
Animals;
Deoxyribonuclease I;
Diabetes Mellitus, Type 1;
DNA*;
Genetic Therapy;
Injections, Intravenous;
Insulin-Secreting Cells*;
Interleukin-10*;
Mice;
Mice, Inbred NOD*;
Plasmids*;
Prevalence;
Veins
- From:Journal of Korean Society of Endocrinology
2000;15(2):262-271
- CountryRepublic of Korea
- Language:Korean
-
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.