Arbuthnot Patrick
Antiviral Gene Therapy Research Unit, Department of Molecular Medicine and Haematology, University of the Witwatersrand Medical School, Wits, South Africa.
Drug News Perspect. 2010 Jul-Aug;23(6):341-50. doi: 10.1358/dnp.2010.23.6.1437713.
Exploiting the RNA interference (RNAi) pathway to inhibit viral gene expression has become an active field of research. The approach has potential for therapeutic application and several viruses are susceptible to RNAi-mediated knockdown. Differences in the characteristics of individual viruses require that viral gene silencing be tailored to specific infections. Important considerations are viral tissue tropism, acute or chronic nature of the infection and the efficiency with which antiviral sequences can be delivered to affected tissue. Both synthetic short interfering RNAs (siRNAs) and expressed RNAi activators are being developed for viral therapy. The sustained silencing of expressed antiviral sequences is useful for countering chronic viral infection. siRNAs, which may be chemically modified to improve specificity and stability, are being developed for knockdown of viruses that cause acute or chronic infections. Preventing viral escape from silencing is important and overcoming this problem using combinatorial RNAi or through silencing of host dependency factors is promising. Although improving delivery efficiency and limiting off-target effects remain obstacles, rapid progress continues to be made in the field and it is likely that the goal of achieving licensed RNAi-based viral therapies will soon be realized.
利用RNA干扰（RNAi）途径抑制病毒基因表达已成为一个活跃的研究领域。该方法具有治疗应用潜力，并且几种病毒对RNAi介导的基因敲低敏感。个别病毒特性的差异要求针对特定感染定制病毒基因沉默。重要的考虑因素包括病毒组织嗜性、感染的急性或慢性性质以及抗病毒序列递送至受影响组织的效率。合成短干扰RNA（siRNA）和表达的RNAi激活剂都正在被开发用于病毒治疗。表达的抗病毒序列的持续沉默对于对抗慢性病毒感染很有用。siRNA可进行化学修饰以提高特异性和稳定性，正在被开发用于敲低引起急性或慢性感染的病毒。防止病毒从沉默中逃逸很重要，使用组合RNAi或通过沉默宿主依赖因子来克服这个问题很有前景。尽管提高递送效率和限制脱靶效应仍然是障碍，但该领域仍在继续取得快速进展，基于RNAi的病毒疗法获得许可的目标可能很快就会实现。
