Dykxhoorn D M, Palliser D, Lieberman J
CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Gene Ther. 2006 Mar;13(6):541-52. doi: 10.1038/sj.gt.3302703.
As soon as RNA interference (RNAi) was found to work in mammalian cells, research quickly focused on harnessing this powerful endogenous and specific mechanism of gene silencing for human therapy. RNAi uses small RNAs, less than 30 nucleotides in length, to suppress expression of genes with complementary sequences. Two strategies can introduce small RNAs into the cytoplasm of cells, where they are active - a drug approach where double-stranded RNAs are administered in complexes designed for intracellular delivery and a gene therapy approach to express precursor RNAs from viral vectors. Phase I clinical studies have already begun to test the therapeutic potential of small RNA drugs that silence disease-related genes by RNAi. This review will discuss progress in developing and testing small RNAi-based drugs and potential obstacles.
一旦发现RNA干扰（RNAi）在哺乳动物细胞中起作用，研究很快就集中于利用这种强大的内源性基因沉默特异性机制进行人类治疗。RNAi利用长度小于30个核苷酸的小RNA来抑制具有互补序列的基因的表达。有两种策略可将小RNA导入细胞的细胞质中使其发挥作用——一种是药物方法，即将双链RNA以设计用于细胞内递送的复合物形式给药；另一种是基因治疗方法，即从病毒载体表达前体RNA。I期临床研究已经开始测试通过RNAi沉默疾病相关基因的小RNA药物的治疗潜力。本综述将讨论基于小RNA干扰的药物研发和测试进展以及潜在障碍。
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