The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic.

By Mark E. Davis. Molecular Pharmaceutics, 2009

968 citations recorded by the source corpus.

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.

Subfields: Biomaterials, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/18c50938fcf660eaf58219c234eb6a853ffbdcd3

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Citations in the corpus

• Nanoparticles in the clinic (2016, methodology): “This system used a cyclodextrinbased particle which contained PEG, an siRNA designed to knockdown RRM2, and a transferrin receptor targeting protein, which when formulated together in a single nanoparticle was successful in achieving knockdown of the protein RRM2 (Figure 2ai).(60,61) A similar strat”
• Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. (2014, background): “The presence of Tf-ligands was shown to be essential for the intracellular delivery and gene silencing efficacy of siRNA nanocomplexes [159, 189].”
• Polyethyleneimine coating enhances the cellular uptake of mesoporous silica nanoparticles and allows safe delivery of siRNA and DNA constructs. (2009, background): “As for most molecular therapies, in vivo delivery is a major hurdle in successful implementation and has sparked a number of strategies to increase siRNA circulatory half-life, facilitate transduction across biological membranes, and achieve cell-specific delivery.(34,35) We propose that packaging o”
• PEGylation as a strategy for improving nanoparticle-based drug and gene delivery (2015, neutral): “NPs and non-targeted, PEGylated CDP NPs, respectively [189].”