Degradable polymeric carrier for the delivery of IL-10 plasmid DNA to prevent autoimmune insulitis of NOD mice
Degradable polymeric carrier for the delivery of IL-10 plasmid DNA to prevent autoimmune insulitis of NOD mice
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DOI：
10.1038/sj.gt.3301334
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发表时间：
2000-12-01
期刊：
影响因子：
5.1
通讯作者：
Kim, SW
中科院分区：
文献类型：
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作者：
Koh, JJ;Ko, KS;Kim, SW
最近，我们报道了可生物降解的聚[α -（4-氨基丁基）- l -乙醇酸]（PAGA）可以凝聚并保护质粒DNA免受DNA酶i的侵害。在本研究中，我们研究了系统给药pCAGGS小鼠IL-10 （mlL-10）表达质粒与PAGA复合物是否可以减少非肥胖糖尿病（NOD）小鼠胰岛素的发展。将PAGA/mlL-10质粒复合物注入3周龄NOD小鼠尾静脉，可维持60 min以上，但10 min内DNA被DNA酶i破坏。血清mlL-10水平在注射后第5天达到峰值，可持续检测9周以上。经静脉注射PAGA/DNA复合物可显著降低12周龄NOD小鼠严重胰岛素炎的发生率（15.7%），比裸DNA注射（34.5%）和未治疗对照组（90.9%）明显降低。综上所述，全身给药pCAGGS mml -10质粒/PAGA复合物可减轻NOD小鼠胰岛素的严重程度。本研究表明，PAGA/DNA复合物具有预防自身免疫性糖尿病的潜力。
Recently, we have reported that biodegradable poly [alpha-(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 (mlL-10) expression plasmid complexed with PAGA can reduce the development of insulitis in non-obese diabetic (NOD) mice. PAGA/mlL-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 mlL-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 mlL-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.