Golzio Muriel, Mazzolini Laurent, Paganin-Gioanni Aurélie, Teissié Justin
IPBS Université P Sabatier and CNRS (UMR 5089), Toulouse, France.
Methods Mol Biol. 2009;555:15-27. doi: 10.1007/978-1-60327-295-7_2.
Short interfering RNAs (siRNAs) represent new potential therapeutic tools, owing to their capacity to induce strong, sequence-specific gene silencing in cells. However, their clinical development requires new, safe, and efficient in vivo siRNA delivery methods. In this study, we report an efficient in vivo approach for targeting gene knockdown in solid tumors by the use of external electric field pulses. We show that gene silencing is efficiently obtained in vivo with chemically synthesized siRNA after targeted electrical delivery in the tumor-bearing mouse. The associated gene silencing was followed on the same animal by fluorescence imaging and confirmed by qPCR. Gene silencing obtained in tumors lasted from 2 to 4 days after a single treatment. Therefore, this method should allow gene function analysis or organ treatment by a localized delivery of siRNAs.
短干扰RNA（siRNA）是一种新的潜在治疗工具，因为它们能够在细胞中诱导强烈的、序列特异性的基因沉默。然而，它们的临床开发需要新的、安全且高效的体内siRNA递送方法。在本研究中，我们报告了一种通过使用外部电场脉冲在实体瘤中靶向基因敲低的高效体内方法。我们表明，在荷瘤小鼠中进行靶向电递送后，化学合成的siRNA能够在体内有效地实现基因沉默。通过荧光成像在同一只动物上跟踪相关的基因沉默，并通过qPCR进行确认。单次治疗后，肿瘤中获得的基因沉默持续2至4天。因此，这种方法应该能够通过局部递送siRNA进行基因功能分析或器官治疗。
