Williford John-Michael, Wu Juan, Ren Yong, Archang Maani M, Leong Kam W, Mao Hai-Quan
Department of Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
Annu Rev Biomed Eng. 2014 Jul 11;16:347-70. doi: 10.1146/annurev-bioeng-071813-105119. Epub 2014 Jun 2.
Inhibiting specific gene expression by short interfering RNA (siRNA) offers a new therapeutic strategy to tackle many diseases, including cancer, metabolic disorders, and viral infections, at the molecular level. The macromolecular and polar nature of siRNA hinders its cellular access to exert its effect. Nanoparticulate delivery systems can promote efficient intracellular delivery. Despite showing promise in many preclinical studies and potential in some clinical trials, siRNA has poor delivery efficiency, which continues to demand innovations, from carrier design to formulation, in order to overcome transport barriers. Previous findings for optimal plasmid DNA delivery cannot be generalized to siRNA delivery owing to significant discrepancy in size and subtle differences in chain flexibility between the two types of nucleic acids. In this review, we highlight the recent advances in improving the stability of siRNA nanoparticles, understanding their intracellular trafficking and release mechanisms, and applying judiciously the promising formulations to disease models.
通过短干扰RNA（siRNA）抑制特定基因表达为在分子水平上攻克包括癌症、代谢紊乱和病毒感染在内的多种疾病提供了一种新的治疗策略。siRNA的大分子和极性性质阻碍了其进入细胞发挥作用。纳米颗粒递送系统可促进高效的细胞内递送。尽管在许多临床前研究中显示出前景，在一些临床试验中也具有潜力，但siRNA的递送效率较低，这仍需要从载体设计到制剂等方面进行创新，以克服转运障碍。由于这两种核酸在大小上存在显著差异以及链柔韧性上存在细微差别，先前关于最佳质粒DNA递送的研究结果不能推广到siRNA递送。在这篇综述中，我们重点介绍了在提高siRNA纳米颗粒稳定性、了解其细胞内运输和释放机制以及明智地将有前景的制剂应用于疾病模型方面的最新进展。
