可电离脂质纳米粒用于siRNA递送的研究进展

Research progress of ionizable lipid nanoparticles for siRNA delivery

小干扰RNA(small interfering RNA,siRNA)是RNA干扰的引发物,通过靶向降解特定信使RNA,抑制基因表达。siRNA对基因调控的高效性与特异性,在疾病治疗方面有重要意义。然而,裸露或未经修饰的siRNA存在稳定性差、易被核酸酶降解、体内半衰期短、入胞效率低等诸多缺陷,导致其成药性低。可电离脂质纳米粒作为新兴的非病毒类核酸递送系统,在提升siRNA成药性上发挥了重要作用。目前已有一款基于可电离脂质纳米粒的siRNA药物获批上市,用于罕见病的治疗。本文介绍了可电离脂质纳米粒在siRNA递送中的研究进展,重点讨论脂质纳米粒各组分对siRNA介导的基因沉默效率的影响,为可电离脂质纳米粒递送siRNA的研究提供参考。

Small interfering RNA(siRNA)is the initiator of RNA interference and inhibits gene expression by targeted degradation of specific messenger RNA.siRNA-mediated gene regulation has high efficiency and specificity and exhibits great significance in the treatment of diseases.However,the naked or unmodified siRNA has poor stability,easy to degrade by nuclease,short half-life,and low intracellular delivery.As an emerging non-viral nucleic acid delivery system,ionizable lipid nanoparticles play an important role in improving the druggability of siRNA.At present,one siRNA drug based on ionizable lipid nanoparticles has been approved for the treatment of rare disease.This review introduces the research progress in ionizable lipid nanoparticles for siRNA delivery,focusing on the effect of each component of lipid nanoparticles on the efficiency of siRNAmediated gene silencing,which provides new references for the studies on ionizable lipid nanocarriers for siRNA delivery.