Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Bearsden Road, Glasgow G61 1QH, UK.
Exp Parasitol. 2012 Sep;132(1):56-61. doi: 10.1016/j.exppara.2011.08.002. Epub 2011 Aug 10.
RNA interference (RNAi) is widely used in Caenorhabiditis elegans to identify essential gene function. In parasitic nematodes RNAi has been reported to result in transcript knockdown of some target genes, but not others, thus limiting its use as a potential functional genomics tool. We recently extended work in Haemonchus contortus to examine why only some genes seem to be susceptible to RNAi and to test RNAi effects in vivo. Here we review our findings, which suggest that site of gene expression influences silencing. This most likely reflects limited uptake of dsRNA from the environment, a phenomenon also observed in other free-living nematodes. We discuss new technologies to improve dsRNA delivery, such as nanoparticles being developed for therapeutic siRNA delivery, and methods to monitor RNAi effects. Alternative approaches will be important in progressing the application of RNAi to identify essential gene function in parasitic nematodes.
RNA 干扰 (RNAi) 在秀丽隐杆线虫中被广泛用于鉴定必需基因的功能。在寄生线虫中,据报道 RNAi 会导致一些靶基因的转录物下调,但不是其他基因,因此限制了它作为一种潜在的功能基因组学工具的使用。我们最近在捻转血矛线虫中扩展了工作,以研究为什么只有一些基因似乎容易受到 RNAi 的影响,并在体内测试 RNAi 的效果。在这里,我们回顾了我们的发现,这些发现表明基因表达的位置会影响沉默。这很可能反映了从环境中摄取 dsRNA 的能力有限,这种现象也在其他自由生活的线虫中观察到。我们讨论了提高 dsRNA 传递的新技术,例如正在开发用于治疗性 siRNA 传递的纳米粒子,以及监测 RNAi 效果的方法。在将 RNAi 应用于鉴定寄生线虫中必需基因的功能方面,替代方法将是重要的。