Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland.
Drug Discov Today. 2015 Jan;20(1):50-64. doi: 10.1016/j.drudis.2014.09.011. Epub 2014 Sep 26.
Huntington's disease (HD) is an incurable genetic neurodegenerative disorder that leads to motor and cognitive decline. It is caused by an expanded polyglutamine tract within the Huntingtin (HTT) gene, which translates into a toxic mutant HTT (muHTT) protein. Although no cure has yet been discovered, novel therapeutic strategies, such as RNA interference (RNAi), antisense oligonucleotides (ASOs), ribozymes, DNA enzymes, and genome-editing approaches, aimed at silencing or repairing the muHTT gene hold great promise. Indeed, several preclinical studies have demonstrated the utility of such strategies to improve HD neuropathology and symptoms. In this review, we critically summarise the main advances and limitations of each gene-silencing technology as an effective therapeutic tool for the treatment of HD.
亨廷顿病（HD）是一种无法治愈的遗传性神经退行性疾病，可导致运动和认知能力下降。它是由亨廷顿蛋白（HTT）基因内的扩展聚谷氨酰胺链引起的，导致毒性突变 HTT（muHTT）蛋白。尽管尚未发现治愈方法，但新型治疗策略，如 RNA 干扰（RNAi）、反义寡核苷酸（ASO）、核酶、DNA 酶和基因组编辑方法，旨在沉默或修复 muHTT 基因，具有很大的潜力。事实上，几项临床前研究已经证明了这些策略在改善 HD 神经病理学和症状方面的有效性。在这篇综述中，我们批判性地总结了每种基因沉默技术的主要进展和局限性，作为治疗 HD 的有效治疗工具。
