In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight
Author(s)Dahlman, James E.; Khan, Omar F.; Jhunjhunwala, Siddharth; Shaw, Taylor E.; Xing, Yiping; Sahay, Gaurav; Bader, Andrew; Bogorad, Roman L.; Yin, Hao; Dong, Yizhou; Jiang, Shan; Seedorf, Danielle; Dave, Apeksha; Sandhu, Kamaljeet Singh; Webber, Matthew; Ruda, Vera M.; Lytton-Jean, Abigail K. R.; Levins, Christopher G.; Langer, Robert; Anderson, Daniel Griffith; ... Show more Show less
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Dysfunctional endothelium contributes to more diseases than any other tissue in the body. Small interfering RNAs (siRNAs) can help in the study and treatment of endothelial cells in vivo by durably silencing multiple genes simultaneously, but efficient siRNA delivery has so far remained challenging. Here, we show that polymeric nanoparticles made of low-molecular-weight polyamines and lipids can deliver siRNA to endothelial cells with high efficiency, thereby facilitating the simultaneous silencing of multiple endothelial genes in vivo. Unlike lipid or lipid-like nanoparticles, this formulation does not significantly reduce gene expression in hepatocytes or immune cells even at the dosage necessary for endothelial gene silencing. These nanoparticles mediate the most durable non-liver silencing reported so far and facilitate the delivery of siRNAs that modify endothelial function in mouse models of vascular permeability, emphysema, primary tumour growth and metastasis.
DepartmentInstitute for Medical Engineering and Science; David H. Koch Institute for Integrative Cancer Research at MIT; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Chemical Engineering; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Nature Publishing Group
Dahlman, James E., Carmen Barnes, Omar F. Khan, Aude Thiriot, Siddharth Jhunjunwala, Taylor E. Shaw, Yiping Xing, et al. “In Vivo Endothelial siRNA Delivery Using Polymeric Nanoparticles with Low Molecular Weight.” Nature Nanotechnology 9, no. 8 (May 11, 2014): 648–655.
Author's final manuscript