Department of Biomedical Sciences, Center of Excellence for Infectious Diseases, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
Trends Mol Med. 2009 Nov;15(11):491-500. doi: 10.1016/j.molmed.2009.09.001. Epub 2009 Oct 19.
Silencing specific gene expression by RNA interference (RNAi) has rapidly become a standard tool for the reverse genetic analysis of gene functions. It also has tremendous potential for managing diseases for which effective treatment is currently unavailable or suboptimal. However, the poor cellular uptake of synthetic small interfering RNAs (siRNAs) is a major impediment for their clinical use. Great progress has been made in recent years to overcome this barrier, and several methods have been described for the in vivo delivery of siRNA. Moreover, the latest advances have focused on achieving targeted siRNA delivery restricted to relevant tissues and cell types in vivo. These approaches are expected to reduce the dose requirement as well as minimize siRNA-induced toxicities, thereby advancing the field of siRNA therapy towards clinical use.
通过 RNA 干扰（RNAi）沉默特定基因的表达已迅速成为基因功能反向遗传学分析的标准工具。它对于管理目前尚无有效或最佳治疗方法的疾病也具有巨大的潜力。然而，合成小干扰 RNA（siRNA）的细胞摄取率低是其临床应用的主要障碍。近年来，在克服这一障碍方面取得了重大进展，并且已经描述了几种用于体内递送 siRNA 的方法。此外，最新的进展集中在实现仅限于体内相关组织和细胞类型的靶向 siRNA 递送上。这些方法有望降低剂量要求并最大程度地减少 siRNA 诱导的毒性，从而推动 siRNA 治疗领域向临床应用发展。
