在细胞外环境中使用铁烯酸脂的siRNA复合物的转化和激活的基氧还原控制
Burcu S Aytar1, John P E Muller, Yukishige Kondo
1Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Journal of the American Chemical Society
|May 25, 2013
概括
具有氧化还原活性的阴性脂质, bis(11-ferrocenylundecyl) dimethylammonium bromide (BFDMA),可以控制小干扰RNA (siRNA) 脂质复杂活性. 减少的BFDMA促进了基因沉默,而氧化的BFDMA可以被激活以控制siRNA传递.
科学领域:
- 生物物理化学 生物物理化学
- 纳米技术纳米技术
- 分子生物学分子生物学
背景情况:
- 阴阳性脂质对于与基因沉默的siRNA等核酸形成脂质组至关重要.
- 在 bis(11-ferrocenylundecyl) dimethylammonium bromide (BFDMA) 中的氧化还原活性铁基组提供了可调节的脂质复杂性质的潜力.
研究的目的:
- 为了研究与氧化还原活性阴阳性脂质BFDMA形成的siRNA脂质组的物理特征和生物活性.
- 为了确定BFDMA的氧化还原状态是否影响脂质复杂性和siRNA递送效率.
主要方法:
- siRNA与BFDMA的复合形成了脂质复合物.
- 脂质组的物理性质的表征,包括纳米结构 (cryo-TEM) 和 ζ 潜力.
- 在细胞环境中对基因沉默活动的评估.
- 在现场激活氧化脂质复合物使用化学还原剂.
主要成果:
- 减少BFDMA的siRNA的脂质组显示出高序列特异性基因沉默.
- 有氧化BFDMA的脂质复合物没有显示基因沉默,与细胞内化不良相关.
- 氧化BFDMA脂质复合物可以被降解剂激活以诱导基因沉默.
- 观察到依赖氧的纳米结构和 ζ 的潜在差异.
- 与等离子体DNA观察到的还氧化控制机制与siRNA保持一致.
结论:
- BFDMA的氧化还原状态提供了一种机制来控制siRNA加载的脂质复合体的活性和递送.
- 脂质复合体的外部激活为细胞系统中控制的siRNA递送提供了一种策略.
- BFDMA的氧化还原反应能力为设计先进的siRNA传递系统提供了新的机会.
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