CBMA (Center of Molecular and Environmental Biology), Department of Biology, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.
CFUM (Center of Physics), Department of Physics, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal.
Curr Drug Targets. 2019;20(1):29-50. doi: 10.2174/1389450119666180703145410.
The possibility of using the RNA interference (RNAi) mechanisms in gene therapy was one of the scientific breakthroughs of the last century. Despite the extraordinary therapeutic potential of this approach, the need for an efficient gene carrier is hampering the translation of the RNAi technology to the clinical setting. Although a diversity of nanocarriers has been described, liposomes continue to be one of the most attractive siRNA vehicles due to their relatively low toxicity, facilitated siRNA complexation, high transfection efficiency and enhanced pharmacokinetic properties. This review focuses on RNAi as a therapeutic approach, the challenges to its application, namely the nucleic acids' delivery process, and current strategies to improve therapeutic efficacy. Additionally, lipid-based nanocarriers are described, and lessons learned from the relation between biophysical properties and biological performance of the dioctadecyldimethylammonium:monoolein (DODAX: MO) system are explored. Liposomes show great potential as siRNA delivery systems, being safe nanocarriers to protect nucleic acids in circulation, extend their half-life time, target specific cells and reduce off-target effects. Nevertheless, several issues related to delivery must be overcome before RNAi therapies reach their full potential, namely target-cell specificity and endosomal escape. Understanding the relationship between biophysical properties and biological performance is an essential step in the gene therapy field.
利用 RNA 干扰 (RNAi) 机制进行基因治疗是上个世纪的科学突破之一。尽管这种方法具有非凡的治疗潜力，但对高效基因载体的需求阻碍了 RNAi 技术向临床应用的转化。尽管已经描述了多种纳米载体，但由于其相对较低的毒性、促进 siRNA 复合、高转染效率和增强的药代动力学特性，脂质体仍然是最有吸引力的 siRNA 载体之一。本文综述了 RNAi 作为一种治疗方法，以及其应用面临的挑战，即核酸的传递过程，以及提高治疗效果的当前策略。此外，还描述了基于脂质的纳米载体，并探讨了从二油酰基丙基二甲基氯化铵：单油酸甘油酯（DODAX:MO）系统的物理性质与生物性能之间的关系中获得的经验教训。脂质体作为 siRNA 递送系统具有很大的潜力，它们是安全的纳米载体，可以保护核酸在循环中的稳定性，延长其半衰期，靶向特定细胞并减少脱靶效应。然而，在 RNAi 疗法充分发挥其潜力之前，还必须克服与递送相关的几个问题，即靶细胞特异性和内涵体逃逸。了解物理性质与生物性能之间的关系是基因治疗领域的重要步骤。
