Salim Lidya, McKim Chris, Desaulniers Jean-Paul
University of Ontario Institute of Technology, Faculty of Science 2000 Simcoe Street North Oshawa ON L1H 7K4 Canada
RSC Adv. 2018 Jun 22;8(41):22963-22966. doi: 10.1039/c8ra03908a. eCollection 2018 Jun 21.
The use of short interfering RNAs (siRNAs) as therapeutics holds great promise, but chemical modifications must first be employed to improve their pharmacokinetic properties. This study evaluates the cellular uptake and knock-down efficacy of cholesterol-modified triazole-linked siRNAs targeting firefly luciferase in the absence of a transfection carrier. These siRNAs displayed low cytotoxicity and excellent dose-dependent knockdown in HeLa cells in the 500 to 3000 nM concentration range, with a 70-80% reduction in firefly luciferase activity. Our results indicate that this modification is compatible with the RNA interference pathway, and is less cytotoxic and more effective than a commercially-available triethylene glycol (TEG) cholesterol modification.
将短干扰RNA（siRNA）用作治疗药物具有很大的前景，但必须首先进行化学修饰以改善其药代动力学性质。本研究评估了在没有转染载体的情况下，靶向萤火虫荧光素酶的胆固醇修饰的三唑连接的siRNA的细胞摄取和敲低效率。这些siRNA在500至3000 nM浓度范围内对HeLa细胞显示出低细胞毒性和优异的剂量依赖性敲低，萤火虫荧光素酶活性降低70-80％。我们的结果表明，这种修饰与RNA干扰途径兼容，并且比市售的三甘醇（TEG）胆固醇修饰具有更低的细胞毒性和更高的效率。
