浅析穿膜肽联合双螺旋RNA结合域技术递送siRNA入胞新策略

A New siRNA Delivery Strategy Based on Cell Penetrating Peptide Combined with Double Stranded RNA Binding Domain

RNAi是真核生物中普遍存在的,能够剔除特定基因表达的监控机制,是传染性疾病及恶性肿瘤基因治疗的理想策略.然而,人体内各种生物膜形成的天然屏障的存在,使得siRNA进行临床应用的效率低下.近年来,研究者们发现了一类能够以高效无耗能方式穿过细胞膜进入细胞内的穿膜肽,它能够通过连接后易位的方式将结合上的siRNA递送入胞.但是,穿膜肽与siRNA结合时,会发生团聚、沉淀而限制其入胞效率.而RNA结合蛋白中存在的双螺旋RNA结合域,可在不改变siRNA结构基础上,结合并屏蔽siRNA的负电荷,协助穿膜肽更好地递送siRNA入胞,发挥特异的基因沉默作用.据此,建立了一种新的具有高效应用潜力的siRNA运输方式,为细胞免疫、基因治疗等临床研究提供一些参考.

RNAi can specifically silent the target genes in eukaryotes, which is a new strategy of gene therapy for infectious diseases and cancer. However, the presence of the biofilm barriers in human body, weakened the efficiency of siRNA clinical application. Recently, researchers have found that cell penetrating peptides can deliver siRNA into the cells through a free energy pathway with high efficiency. However, when cationic cell penetrating peptides mix with the anionic siRNA, it occurres precipitation, which limits their entry into cells. A recent study found that the double-stranded RNA binding domain can shield the negative charge of the siRNA without changing the constructs, which can be used to assist cell penetrating peptides delivering siRNA into cells to accomplish the mission. Thereby, a new efficient siRNA delivery application has been established, which can help provide the theoretical basis for cellular immunity and gene therapy applications.