Department of Chemical, Biological and Pharmaceutical Engineering, Newark School of Engineering, New Jersey Institute of Technology, Newark, NJ, 07102, USA.
Adv Healthc Mater. 2016 Nov;5(21):2715-2731. doi: 10.1002/adhm.201600418. Epub 2016 Oct 4.
With the dearth of effective treatment options for prominent diseases including Ebola and cancer, RNA interference (RNAi), a sequence-specific mechanism for genetic regulation that can silence nearly any gene, holds the promise of unlimited potential in treating illness ever since its discovery in 1999. Given the large size, unstable tertiary structure in physiological conditions and negative charge of small interfering RNAs (siRNAs), the development of safe and effective delivery vehicles is of critical importance in order to drive the widespread use of RNAi therapeutics into clinical settings. Immense amounts of time and billions of dollars have been devoted into the design of novel and diverse delivery strategies, and there are a handful of delivery systems that have been successfully translated into clinic. This review provides an introduction to the in vivo barriers that need to be addressed by siRNA delivery systems. We also discuss the progress up to the most effective and clinically advanced siRNA delivery systems including liposomal, polymeric and siRNA conjugate delivery systems, as well as their design to overcome the challenges.
由于埃博拉和癌症等突出疾病缺乏有效治疗方法,RNA 干扰 (RNAi) 作为一种可特异性沉默几乎任何基因的遗传调控机制,自 1999 年发现以来,在治疗疾病方面具有巨大的潜在应用价值。鉴于小干扰 RNA(siRNA)的体积大、生理条件下三级结构不稳定和带负电荷等特性,开发安全有效的递送载体对于推动 RNAi 疗法广泛应用于临床至关重要。人们投入了大量的时间和数十亿美元用于设计新型多样化的递送策略,并且已经有一些递送系统成功转化为临床应用。本综述介绍了 siRNA 递送系统需要克服的体内障碍。我们还讨论了迄今为止最有效和临床最先进的 siRNA 递送系统的进展,包括脂质体、聚合物和 siRNA 缀合物递送系统,以及它们克服挑战的设计。