Guo Jianfeng, Fisher Karen A, Darcy Raphael, Cryan John F, O'Driscoll Caitriona
School of Pharmacy, University College Cork, Cork, Ireland.
Mol Biosyst. 2010 Jul;6(7):1143-61. doi: 10.1039/c001050m. Epub 2010 Apr 29.
Gene silencing using RNA-interference, first described in mammalian systems almost a decade ago, is revolutionizing therapeutic target validation efforts both in vitro and in vivo. Moreover, the potential for using short interfering RNA (siRNA) as a therapy in its own right is also progressing at a significant pace. However, the widespread use of such approaches is contingent on having appropriate systems to achieve clinically appropriate, safe, and efficient delivery of siRNA. There are many physicochemical and biological barriers to such delivery, and a growing emphasis on the design and characterisation of non-viral technologies that will overcome these barriers and expedite targeted delivery. This review discusses the considerations and challenges associated with use of siRNA-based therapeutics, including stability and off-target effects. Speculation is made on the properties of an ideal delivery system and the non-viral delivery approaches used to date, both in vitro and in vivo, are classified and discussed. Moreover, the ability of cyclodextrin-based delivery vectors to fulfil many of the criteria of an ideal delivery construct is also elaborated.
利用RNA干扰进行基因沉默，大约十年前在哺乳动物系统中首次被描述，正在彻底改变体外和体内的治疗靶点验证工作。此外，将短干扰RNA（siRNA）本身用作一种治疗方法的潜力也在快速发展。然而，此类方法的广泛应用取决于是否拥有合适的系统，以实现临床上合适、安全且高效的siRNA递送。这种递送存在许多物理化学和生物学障碍，并且越来越强调设计和表征能够克服这些障碍并加速靶向递送的非病毒技术。本综述讨论了与基于siRNA的治疗相关的考虑因素和挑战，包括稳定性和脱靶效应。对理想递送系统的特性进行了推测，并对迄今在体外和体内使用的非病毒递送方法进行了分类和讨论。此外，还阐述了基于环糊精的递送载体满足理想递送构建体许多标准的能力。
