Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112-5820, USA.
Adv Drug Deliv Rev. 2012 Sep;64(12):1341-57. doi: 10.1016/j.addr.2011.09.002. Epub 2011 Sep 10.
RNA interference (RNAi) is a sequence-specific post-transcriptional gene silencing technique developed with dramatically increasing utility for both scientific and therapeutic purposes. Short interfering RNA (siRNA) is currently exploited to regulate protein expression relevant to many therapeutic applications, and commonly used as a tool for elucidating disease-associated genes. Osteoporosis and their associated osteoporotic fragility fractures in both men and women are rapidly becoming a global healthcare crisis as average life expectancy increases worldwide. New therapeutics are needed for this increasing patient population. This review describes the diversity of molecular targets suitable for RNAi-based gene knock down in osteoclasts to control osteoclast-mediated excessive bone resorption. We identify strategies for developing targeted siRNA delivery and efficient gene silencing, and describe opportunities and challenges of introducing siRNA as a therapeutic approach to hard and connective tissue disorders.
RNA 干扰 (RNAi) 是一种序列特异性的转录后基因沉默技术，在科学和治疗方面的应用越来越广泛。短干扰 RNA (siRNA) 目前被用于调节与许多治疗应用相关的蛋白质表达，并且通常被用作阐明与疾病相关基因的工具。随着全球平均预期寿命的增加，男性和女性的骨质疏松症及其相关的骨质疏松性脆性骨折迅速成为全球医疗保健危机。对于这个不断增加的患者群体，需要新的治疗方法。本文综述了适用于 RNAi 介导的破骨细胞基因敲低以控制破骨细胞介导的过度骨吸收的分子靶点的多样性。我们确定了开发靶向 siRNA 递送和有效基因沉默的策略，并描述了将 siRNA 作为治疗硬组织和结缔组织疾病的方法的机会和挑战。
