用于亨廷顿病的寡核苷酸治疗方法。
Oligonucleotide therapeutic approaches for Huntington disease.
机构信息
Alnylam Pharmaceuticals Inc., Cambridge, Massachusetts, USA.
出版信息
J Clin Invest. 2011 Feb;121(2):500-7. doi: 10.1172/JCI45130. Epub 2011 Feb 1.
Abstract
Huntington disease is an autosomal dominant neurodegenerative disorder caused by a toxic expansion in the CAG repeat region of the huntingtin gene. Oligonucleotide approaches based on RNAi and antisense oligonucleotides provide promising new therapeutic strategies for direct intervention through reduced production of the causative mutant protein. Allele-specific and simultaneous mutant and wild-type allele-lowering strategies are being pursued with local delivery to the brain, each with relative merits. Delivery remains a key challenge for translational success, especially with chronic therapy. The potential of disease-modifying oligonucleotide approaches for Huntington disease will be revealed as they progress into clinical trials.
摘要
亨廷顿病是一种常染色体显性神经退行性疾病，由亨廷顿基因 CAG 重复区域的毒性扩张引起。基于 RNAi 和反义寡核苷酸的寡核苷酸方法为通过减少致病突变蛋白的产生提供了有前途的新治疗策略。正在通过局部递送到大脑来追求针对特定等位基因和同时降低突变型和野生型等位基因的策略，每种策略都有其相对的优点。对于转化成功来说，传递仍然是一个关键挑战，尤其是在慢性治疗中。随着疾病修饰寡核苷酸方法进入临床试验，它们在亨廷顿病中的潜力将逐渐显现。
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