The First Targeted Delivery of siRNA in Humans via a Self-Assembling, Cyclodextrin Polymer-Based Nanoparticle: From Concept to Clinic
- Creators
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Davis, Mark E.
Abstract
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
Additional Information
© 2009 American Chemical Society. Publication Date (Web): March 6, 2009. Received: January 15, 2009. Accepted: March 6, 2009. I thank all my coauthors who are listed on the references provided. I especially thank Dr. Jeremy Heidel who provided the leadership in bringing CALAA-01 from the benchtop to the bedside. Lastly, I thank the patients who willingly participated in the clinical trial. M.E. Davis has been a consultant to and has financial interest in Calando PharmaceuticalsAdditional details
- Eprint ID
- 15195
- DOI
- 10.1021/mp900015y
- Resolver ID
- CaltechAUTHORS:20090820-150240761
- Created
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2009-09-08Created from EPrint's datestamp field
- Updated
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2021-11-08Created from EPrint's last_modified field