*Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.
Biochem J. 2013 Oct 15;455(2):133-47. doi: 10.1042/BJ20130950.
The specificity of RNAi and its ability to silence 'undruggable' targets has made inhibition of gene expression in T-cells with siRNAs an attractive potential therapeutic strategy for the treatment of inflammatory disease, cancer and infection. However, delivery of siRNAs into primary T-cells represents a major hurdle to their use as potential therapeutic agents. Recent advances in siRNA delivery through the use of electroporation/nucleofection, viral vectors, peptides/proteins, nanoparticles, aptamers and other agents have now enabled efficient gene silencing in primary T-cells both in vitro and in vivo. Overcoming such barriers in siRNA delivery offers exciting new prospects for directly targeting T-cells systemically with siRNAs, or adoptively transferring T-cells back into patients following ex vivo manipulation with siRNAs. In the present review, we outline the challenges in delivering siRNAs into primary T-cells and discuss the mechanism and therapeutic opportunities of each delivery method. We emphasize studies that have exploited RNAi-mediated gene silencing in T-cells for the treatment of inflammatory disease, cancer and infection using mouse models. We also discuss the potential therapeutic benefits of manipulating T-cells using siRNAs for the treatment of human diseases.
RNAi 的特异性及其沉默“不可成药”靶标的能力，使得利用 siRNA 抑制 T 细胞中的基因表达成为治疗炎症性疾病、癌症和感染的一种有吸引力的潜在治疗策略。然而，将 siRNA 递送至原代 T 细胞是将其用作潜在治疗剂的主要障碍。最近，通过电穿孔/核转染、病毒载体、肽/蛋白、纳米颗粒、适体和其他试剂来递送 siRNA 的进展，使得在体外和体内都能够有效地在原代 T 细胞中进行基因沉默。克服 siRNA 递送上的这些障碍，为通过 siRNA 系统地直接靶向 T 细胞，或在对 T 细胞进行离体操作后通过 siRNA 将 T 细胞回输至患者体内提供了令人兴奋的新前景。在本综述中，我们概述了将 siRNA 递送至原代 T 细胞所面临的挑战，并讨论了每种递送方法的机制和治疗机会。我们强调了利用 RNAi 介导的基因沉默在小鼠模型中治疗炎症性疾病、癌症和感染的研究。我们还讨论了利用 siRNA 操纵 T 细胞治疗人类疾病的潜在治疗益处。
