siRNA肺部给药及其在肺部疾病治疗中的应用  

Pulmonary Delivery of Therapeutic siRNA for Lung Diseases

作　　者：谢彧雯[1] 汤玥[1] 刘云[1] 陈菁[1] 段文佳[1] 

机构地区：[1]中国药科大学药学院,江苏南京210009

出　　处：《药物生物技术》2016年第4期372-376,共5页Pharmaceutical Biotechnology

基　　金：大学生创新创业训练计划项目资助(No.XZ15179)

摘　　要：RNA干扰(RNAi)是一种转录后的基因沉默机制,从发现至今已逐渐成为疾病治疗的新手段。小干扰RNA(siRNA)是RNAi过程中的效应分子,已作为药物处于临床研究的不同阶段。以病毒或肺内源性基因为靶点的siRNA在肺部病毒感染、慢性炎症性肺疾病、肺癌等肺部疾病的治疗中显示出了良好的应用前景。siRNA用于肺部疾病的治疗既可以通过注射给药达到病灶部位,也可采取局部给药的方式将siRNA投递至肺部。与注射给药相比,siRNA的肺部给药具有所需剂量少、系统副作用小、直接到达靶部位、核酸酶活性低等优点。以RNAi为策略,通过肺部给药将siRNA局部作用于靶部位,是siRNA治疗肺部疾病的研究热点。文章从肺部疾病的相关靶点出发,介绍了siRNA在肺疾病治疗中的研究进展,总结了当前应对siRNA肺部给药屏障的策略,并根据给药方式的研究情况概括了siRNA肺部给药的发展趋势。RNA interference（ RNAi） is a mechanism of the post-transcriptional gene silencing,which becomes an attractive treatment for various diseases. As the effector molecule which mediates RNAi,small interfering RNA（ siRNA） has been used as therapeutic agents in various stages of clinical research. Some of lung diseases such as asthma,syncytial virus infection,and metastatic lung cancer can be treated efficiently by siRNA that specifically targets virus or endogenous gene. SiRNA delivery to the lung could be achieved either by local delivery or systemic delivery. The superiority of the former route includes the relative stability in the airway as a result of the absence of serum and lower nuclease activity. Targeted,local delivery of siRNA to the lungs especially via inhalation is believed to be the most promising administration route in future development. This paper reviews the application of therapeutic siRNA in pulmonary diseases,the barriers of siRNA delivery to the lung and pulmonary route of siRNA administration,and it summarizes the trend of siRNA pulmonary delivery based on the latest development for the treatment of various lung diseases.

关 键 词：RNA干扰 小干扰RNA 基因沉默 肺部疾病 肺部给药 吸入 

分 类 号：R453[医药卫生—治疗学] R56[医药卫生—临床医学]