Leng Qixin, Woodle Martin C, Lu Patrick Y, Mixson A James
Department of Pathology, University of Maryland Baltimore, MSTF Building, 10 South Pine Street, Baltimore, MD 21201, USA.
Drugs Future. 2009 Sep;34(9):721. doi: 10.1358/dof.2009.034.09.1413267.
Sequence-specific gene silencing with small interfering RNA (siRNA) has transformed basic science research, and the efficacy of siRNA therapeutics toward a variety of diseases is now being evaluated in pre-clinical and clinical trials. Despite its potential value, the highly negatively charged siRNA has the classic delivery problem of requiring transport across cell membranes to the cytosol. Consequently, carrier development for siRNA delivery is one of the most important problems to solve before siRNA can achieve widespread clinical use. An assortment of non-viral carriers including liposomes, peptides, polymers, and aptamers are being evaluated for their ability to shepherd siRNA to the target tissue and cross the plasma membrane barrier into the cell. Several promising carriers with low toxicity and increased specificity for disease targets have emerged for siRNA-based therapeutics. This review will discuss non-viral approaches for siRNA therapeutics, with particular focus on synthetic carriers for in vivo systemic delivery of siRNA.
小干扰RNA（siRNA）介导的序列特异性基因沉默改变了基础科学研究，目前，siRNA疗法针对多种疾病的疗效正在临床前和临床试验中进行评估。尽管具有潜在价值，但高度带负电荷的siRNA存在经典的递送问题，即需要穿过细胞膜转运至细胞质。因此，在siRNA能够广泛应用于临床之前，开发用于递送siRNA的载体是最重要的待解决问题之一。包括脂质体、肽、聚合物和适体在内的多种非病毒载体正在接受评估，以确定它们将siRNA引导至靶组织并穿过质膜屏障进入细胞的能力。对于基于siRNA的疗法，已经出现了几种毒性低且对疾病靶点特异性增强的有前景的载体。本综述将讨论siRNA疗法的非病毒方法，特别关注用于siRNA体内全身递送的合成载体。
