新的poly ((d-glucaramidoamine) 诱导DNA纳米粒子的形成,并有效地将基因传递到哺乳动物细胞中
Yemin Liu1, Laura Wenning, Matthew Lynch
1Department of Chemistry, University of Cincinnati, Cincinnati, Ohio 45221-0172, USA.
Journal of the American Chemical Society
|June 17, 2004
概括
合成了四种新的含碳水化合物的聚合物,以减少基因传递中的毒性. 这些聚合物有效地将等离子体DNA输入细胞,具有高效率和低毒性,与传统方法相匹配.
科学领域:
- 生物材料科学 生物材料科学
- 聚合物化学 聚合物化学
- 基因传递系统是基因传递系统.
背景情况:
- 传统的聚合物核酸输送车辆往往表现出高毒性.
- 开发更安全,更有效的基因传递系统对于治疗应用至关重要.
研究的目的:
- 设计和合成新型的聚糖胺含碳水化合物共体.
- 与传统聚乙烯胺 (PEI) 相比,评估这些新聚合物的基因传递效率和毒性.
主要方法:
- 通过多重凝结合成四种多糖胺 (1-4) 的合成.
- 使用粘度测量,NMR,凝电泳,动态光散射和TEM进行表征.
- 在BHK-21细胞的体外基因传递研究中,使用 luciferase 记者基因.
主要成果:
- 聚合物1-4证明了塑体DNA (pDNA) 的有效结合和紧缩到纳米粒子 (多重复) 中.
- 合成的聚合物具有低毒性和高基因传递效率,聚合物4的性能与线性PEI相美.
- 增强的基因传递可能与由于氨基基团的质子化而产生的质子海绵效应有关.
结论:
- 新型的多-d-葡萄糖胺胺 (poly-d-glucaramidoamine) 是一种有前途的低毒性基因传递载体.
- 特别是聚合物4显示出有效的非病毒基因疗法应用的巨大潜力.
- 对质子海绵机制的进一步调查可以优化这些基于碳水化合物的聚合物,以改善基因传递.
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