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

• Published in: Molecular pharmaceutics Vol. 6; no. 3; pp. 659 - 668
• Main Author: Davis, Mark E
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01-06-2009
• Subjects: Animals; Cellulose - chemistry; Cyclodextrins - chemistry; Humans; Mice; Nanoparticles; Nanotechnology - methods; Polyethylene Glycols - chemistry; RNA Interference; RNA, Small Interfering - chemical synthesis; RNA, Small Interfering - chemistry; Transferrin - chemistry; clinical trial; targeted delivery; targeted nanoparticle; siRNA; CALAA-01
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/mp900015y

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.