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.
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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.
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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). https://doi.org/10.1038/sj.gt.3301334
- gene therapy
- NOD mouse
- poly [α-(4-aminobutyl)-L-glycolic acid] (PAGA)
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