Inhalable siRNA: Potential as a therapeutic agent in the lungs
Inhalable siRNA: Potential as a therapeutic agent in the lungs
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DOI：
10.1021/mp070048k
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发表时间：
2008-07-01
影响因子：
4.9
通讯作者：
Cryan, Sally-Ann
中科院分区：
文献类型：
--
作者：
Durcan, Niamh;Murphy, Charlotte;Cryan, Sally-Ann
RNA 干扰 (RNAi) 作为分子生物学工具和潜在的治疗剂越来越受欢迎。 RNAi 是一种自然发生的基因调控机制，与其他基因/反义疗法相比具有许多优势，包括抑制特异性、效力、分子尺寸小以及毒性作用（例如免疫反应）风险降低。通过吸入将 RNAi 有针对性地局部输送到肺部，为治疗一系列以前无法治疗或控制不佳的呼吸系统疾病提供了独特的机会。在这篇及时的综述中，我们研究了 RNAi 在肺部治疗一系列疾病的潜在应用，包括炎症和免疫疾病、囊性纤维化、传染病和癌症。 2006年，Alnylam启动了第一个吸入性siRNA治疗呼吸道合胞病毒的1期临床研究。如果要实现其治疗潜力，则必须开发安全有效的方法，将小干扰 RNA (siRNA) 靶向递送至肺部。因此，在这篇综述中，我们还介绍了体外将 siRNA 递送至气道细胞的最新进展，以及迄今为止将 siRNA 体内递送至肺部以治疗一系列疾病的工作。
RNA interference (RNAi) is gaining increasing popularity both as a molecular biology tool and as a potential therapeutic agent. RNAi is a naturally occurring gene regulatory mechanism, which has a number of advantages over other gene/antisense therapies including specificity of inhibition, potency, the small size of the molecules and the diminished risk of toxic effects, e.g., immune responses. Targeted, local delivery of RNAi to the lungs via inhalation offers a unique opportunity to treat a range of previously untreatable or poorly controlled respiratory conditions. In this timely review we look at the potential applications of RNAi in the lungs for the treatment of a range of diseases including inflammatory and immune conditions, cystic fibrosis, infectious disease and cancer. In 2006 Alnylam initiated the first phase 1 clinical study of an inhaled siRNA for the treatment of respiratory syncytial virus. If its potential as a therapeutic is to be realized, then safe and efficient means of targeted delivery of small interfering RNA (siRNA) to the lungs must be developed. Therefore in this review we also present the latest developments in siRNA delivery to airway cells in vitro and the work to date on in vivo delivery of siRNA to the lungs for the treatment of a range of diseases.