Gonzalez-Alegre Pedro, Paulson Henry L
University of Iowa, Iowa City, IA, USA.
Nat Clin Pract Neurol. 2007 Jul;3(7):394-404. doi: 10.1038/ncpneuro0551.
As an evolutionarily conserved cellular pathway to regulate endogenous gene expression, RNA interference (RNAi) has been implicated in diverse biological processes. Biologists now routinely exploit this cellular pathway to suppress virtually any target gene in a sequence-specific manner, including dominantly acting genes that cause incurable neurodegenerative disorders. The development of RNAi as potential therapy for such diseases has generated considerable interest, partly because of the success of early studies of therapeutic RNAi in rodent models for a range of neurodegenerative diseases. In this article, we review the progress of RNAi therapy to date, and assess the challenges ahead for the application of such therapy to neurodegenerative diseases. We discuss the various strategies that might be used to achieve this goal, outline the preclinical studies that have already been completed, and highlight the experimental questions that need to be answered before human clinical trials can begin.
作为一种进化上保守的调节内源性基因表达的细胞途径，RNA干扰（RNAi）已涉及多种生物学过程。生物学家现在经常利用这种细胞途径以序列特异性方式抑制几乎任何靶基因，包括导致无法治愈的神经退行性疾病的显性作用基因。RNAi作为此类疾病的潜在疗法的发展引起了相当大的兴趣，部分原因是治疗性RNAi在一系列神经退行性疾病的啮齿动物模型中的早期研究取得了成功。在本文中，我们回顾了迄今为止RNAi治疗的进展，并评估了将这种疗法应用于神经退行性疾病面临的挑战。我们讨论了可能用于实现这一目标的各种策略，概述了已经完成的临床前研究，并强调了在人类临床试验开始之前需要回答的实验问题。
