The First Targeted Delivery of siRNA in Humans via a Self-Assembling, Cyclodextrin Polymer-Based Nanoparticle: From Concept to Clinic

被引：746
作者：
Davis, Mark E. [1 ]
机构：
[1] CALTECH, Pasadena, CA 91125 USA
来源：
MOLECULAR PHARMACEUTICS | 2009年 / 6卷 / 03期
关键词：
CALAA-01; siRNA; targeted delivery; targeted nanoparticle; clinical trial; CARBOHYDRATE-CONTAINING POLYCATIONS; GENE DELIVERY; TUMOR-GROWTH; IN-VITRO; KINETICS; CELL; INHIBITORS; VEHICLE; IMPACT;
D O I：
10.1021/mp900015y
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Experimental therapeutics developed to exploit RNA interference (RNAi) are now in clinical studies. Here, the translation from concept to clinic for the first experimental therapeutic to provide targeted delivery of synthetic, small interfering RNA (siRNA) in humans is described. This targeted, nanoparticle formulation of siRNA, denoted as CALAA-01, consists of a cyclodextrin-containing polymer (CDP), a polythethylene glycol (PEG) steric stabilization agent, and human transferrin (Tf) as a targeting ligand for binding to transferrin receptors (TfR) that are typically upregulated on cancer cells. The four component formulation is self-assembled into nanoparticles in the pharmacy and administered intravenously (iv) to patients. The designed features of this experimental therapeutic are described, and their functions illustrated.
引用
收藏
页码：659 / 668
页数：10
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