Department of Nephrology and Endocrinology, University of Tokyo School of Medicine, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Nat Rev Nephrol. 2011 May 24;7(7):407-15. doi: 10.1038/nrneph.2011.61.
Current treatments for glomerulonephritis are not satisfactory, and the development of new therapies would be indispensable. Short interfering RNAs (siRNAs) are promising candidates for molecular therapy because of their strong and specific gene-silencing effects. Despite rapid progress in research into the therapeutic uses of siRNAs, however, many hurdles must be overcome before siRNA-based therapies can be brought to the clinic. Most in vivo studies of siRNA-based therapy have been limited to local administration or delivery to specific target organs, including the liver. Therapies based on siRNAs for patients with glomerulonephritis show promise, although tissue-specific protocols using siRNAs have not yet been established for this indication. This Review aims to provide an overview of the current challenges in siRNA-based therapy, primarily with respect to glomerular targeting. In addition, novel delivery approaches for glomerulus-targeted, siRNA-based therapies are described.
目前针对肾小球肾炎的治疗方法并不令人满意，因此需要开发新的疗法。由于短干扰 RNA（siRNA）具有强大且特异性的基因沉默作用，因此它是一种很有前途的分子治疗候选物。然而，尽管 siRNA 在治疗应用方面的研究进展迅速，但在将基于 siRNA 的疗法推向临床之前，还必须克服许多障碍。大多数基于 siRNA 的治疗的体内研究仅限于局部给药或递送至特定的靶器官，包括肝脏。基于 siRNA 的治疗方法对肾小球肾炎患者具有前景，尽管尚未针对该适应症建立基于 siRNAs 的组织特异性方案。本综述旨在概述基于 siRNA 的治疗目前所面临的挑战，主要是肾小球靶向方面的挑战。此外，还描述了用于肾小球靶向的基于 siRNA 的治疗的新型递药方法。
