硫代磷酸酯刺激人细胞对小干扰RNA的摄取。
Phosphorothioate-stimulated uptake of short interfering RNA by human cells.
作者信息
Overhoff Marita, Sczakiel Georg
机构信息
Institut für Molekulare Medizin, Universität zu Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
出版信息
EMBO Rep. 2005 Dec;6(12):1176-81. doi: 10.1038/sj.embor.7400535.
Abstract
The cellular delivery of short interfering RNA (siRNA) is a main hurdle in therapeutic drug development. Here, we describe that phosphorothioate (PTO)-derived oligonucleotides stimulate the physical cellular uptake of siRNA in trans in human cells. This is reflected by an apparent dose-dependent siRNA-mediated suppression of lamin A/C in primary human umbilical vein endothelial cells. The PTO-stimulated cellular uptake in trans is concentration dependent, length dependent, related to the phosphorothioate chemistry but not sequence specific. We provide experimental evidence to support a caveolin-mediated uptake mechanism. In sum, this work strongly suggests the exploration of PTOs as facilitators in the delivery of biologically active siRNA to mammalian cells.
摘要
短干扰RNA（siRNA）的细胞递送是治疗药物开发中的一个主要障碍。在此，我们描述了硫代磷酸酯（PTO）衍生的寡核苷酸可刺激人细胞中siRNA的物理性细胞摄取。这在原代人脐静脉内皮细胞中表现为siRNA介导的层粘连蛋白A/C的明显剂量依赖性抑制。PTO刺激的细胞摄取是浓度依赖性、长度依赖性的，与硫代磷酸酯化学性质有关，但不具有序列特异性。我们提供了实验证据来支持小窝蛋白介导的摄取机制。总之，这项工作有力地表明，可探索将PTO用作将生物活性siRNA递送至哺乳动物细胞的促进剂。
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