核酸与葡萄糖核酸的相互作用
Michael J Palte1, Ronald T Raines
1Medical Scientist Training Program, Molecular & Cellular Pharmacology Graduate Training Program, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Journal of the American Chemical Society
|March 10, 2012
概括
哺乳动物细胞通过由阳离子细胞表面糖形成的屏障阻止核酸的吸收. 移除这些糖增加了脂质核酸结合物的进入细胞的速度.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 哺乳动物细胞具有固有的机制来限制外来核酸的进入.
- 血膜的脂质双层是已知的屏障,但存在其他物理化学屏障.
- 了解这些障碍对于基因治疗和基于核酸的药物输送至关重要.
研究的目的:
- 确定和描述哺乳动物细胞中核酸吸收的第二个物理化学障碍.
- 开发和利用光脂质-寡核酸结合物作为研究核酸-细胞相互作用的探针.
- 为了研究细胞表面葡萄糖成分在调节核酸进入中的作用.
主要方法:
- 用光标记的脂质-DNA寡核酸合物的合成.
- 结合体与哺乳动物细胞的化,以评估结合和保留.
- 使用修饰或枯竭的葡萄糖成分 (例如缺乏酸) 的细胞系.
- 调查化脂质合并对合物吸收的影响.
主要成果:
- 脂质-寡核酸结合体很容易融入血,但随后被排出.
- 寡核酸的长度与结合体驱逐的速率具有正相关性.
- 结合体的结合在缺乏阳离子甘油成分 (酸,糖氨基甘油) 的细胞中显著增强.
- 摄取量也增加在细胞预先处理了酸性脂质.
结论:
- 细胞表面的阳离子寡糖化物作为核酸吸收的重要障碍.
- 这种阳离子屏障影响了基因组的稳定性,并对基因和siRNA传递提出了挑战.
- 调节细胞表面电荷或葡萄糖成分可能是提高核酸输送效率的一种策略.
相关概念视频
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