Hutson Thomas H, Foster Edmund, Moon Lawrence D F, Yáñez-Muñoz Rafael J
1 Neurorestoration Group, Wolfson Centre for Age-Related Diseases, King's College London , Guy's Campus, London SE1 1UL, United Kingdom .
Hum Gene Ther Methods. 2014 Feb;25(1):14-32. doi: 10.1089/hgtb.2013.016. Epub 2013 Nov 1.
RNA silencing is an established method for investigating gene function and has attracted particular interest because of the potential for generating RNA-based therapeutics. Using lentiviral vectors as an efficient delivery system that offers stable, long-term expression in postmitotic cells further enhances the applicability of an RNA-based gene therapy for the CNS. In this review we provide an overview of both lentiviral vectors and RNA silencing along with design considerations for generating lentiviral vectors capable of RNA silencing. We go on to describe the current preclinical data regarding lentiviral vector-mediated RNA silencing for CNS disorders and discuss the concerns of side effects associated with lentiviral vectors and small interfering RNAs and how these might be mitigated.
RNA沉默是一种用于研究基因功能的既定方法，由于具有生成基于RNA的疗法的潜力，它引起了特别的关注。使用慢病毒载体作为一种有效的递送系统，该系统可在有丝分裂后细胞中实现稳定、长期的表达，这进一步提高了基于RNA的基因疗法在中枢神经系统中的适用性。在这篇综述中，我们概述了慢病毒载体和RNA沉默，以及用于生成能够进行RNA沉默的慢病毒载体的设计考量。我们接着描述了目前关于慢病毒载体介导的RNA沉默用于中枢神经系统疾病的临床前数据，并讨论了与慢病毒载体和小干扰RNA相关的副作用问题，以及如何减轻这些问题。
