Mangala Lingegowda S, Han Hee Dong, Lopez-Berestein Gabriel, Sood Anil K
Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Methods Mol Biol. 2009;555:29-42. doi: 10.1007/978-1-60327-295-7_3.
Discovery of RNA interference (RNAi) has been one of the most important findings in the last ten years. In recent years, small interfering RNA (siRNA)-mediated gene silencing is beginning to show substantial promise as a new treatment modality in preclinical studies because of its robust gene selective silencing. However, until recently, delivery of siRNA in vivo was a major impediment to its use as a therapeutic modality. We have used a neutral liposome, 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC), for highly efficient in vivo siRNA delivery. Using siRNA tagged with Alexa-555, incorporated in DOPC liposomes, we have demonstrated efficient intra-tumoral delivery following either intraperitoneal or intravenous injection. Furthermore, EphA2-targeted siRNA in DOPC liposomes showed significant target modulation and anti-tumor efficacy.
RNA干扰（RNAi）的发现是过去十年中最重要的发现之一。近年来，小干扰RNA（siRNA）介导的基因沉默因其强大的基因选择性沉默作用，在临床前研究中作为一种新的治疗方式开始展现出巨大的潜力。然而，直到最近，siRNA在体内的递送仍是其作为治疗方式应用的主要障碍。我们使用了一种中性脂质体，1,2 - 二油酰 - sn - 甘油 - 3 - 磷脂酰胆碱（DOPC），用于高效的体内siRNA递送。通过将标记有Alexa - 555的siRNA掺入DOPC脂质体中，我们已经证明在腹腔或静脉注射后能实现高效的肿瘤内递送。此外，DOPC脂质体中靶向EphA2的siRNA显示出显著的靶点调节作用和抗肿瘤功效。
