Jagannath Aarti, Wood Matthew
Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK.
Brief Funct Genomic Proteomic. 2007 Mar;6(1):40-9. doi: 10.1093/bfgp/elm005. Epub 2007 May 3.
Neurodegenerative disorders represent a major class of disorders for which thus far any effective small molecule drug therapy has failed to emerge. RNA interference (RNAi), by which disease genes such as those identified for spino-cerebellar ataxia and Huntington's disease can be specifically silenced, has great potential in becoming a successful therapeutic strategy for these diseases. RNAi has shown therapeutic value in vitro and in animal disease models and clinical trials are currently on their way. However, there are problems, such as toxicity due to non-specific silencing, generation of immune responses and over-saturation of RNAi pathway components that must be overcome in order to establish RNAi as a safe and effective therapy. Current research on the endogenous roles of RNAi, through the action of microRNAs, has offered much knowledge to optimise the exploitation of RNAi.
神经退行性疾病是一大类疾病，迄今为止尚未出现任何有效的小分子药物疗法。RNA干扰（RNAi）可特异性沉默诸如脊髓小脑共济失调和亨廷顿舞蹈症等疾病相关基因，在成为这些疾病的成功治疗策略方面具有巨大潜力。RNAi已在体外和动物疾病模型中显示出治疗价值，目前临床试验正在进行中。然而，要将RNAi确立为一种安全有效的疗法，还必须克服一些问题，如非特异性沉默导致的毒性、免疫反应的产生以及RNAi途径成分的过度饱和。目前通过微小RNA的作用对RNAi内源性作用的研究，为优化RNAi的应用提供了很多知识。
