In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight
Author(s)
Dahlman, James E.; Jhunjhunwala, Siddharth; Shaw, Taylor E.; Xing, Yiping; Sahay, Gaurav; Bader, Andrew; Yin, Hao; Dong, Yizhou; Jiang, Shan; Seedorf, Danielle; Dave, Apeksha; Sandhu, Kamaljeet Singh; Webber, Matthew; Lytton-Jean, Abigail K. R.; Levins, Christopher G.; Anderson, Daniel Griffith; Khan, Omar Fizal; Bogorad, Roman; Ruda, Vera; Langer, Robert S; ... Show more Show less
DownloadAnderson_In vivo endothelial.pdf (536.6Kb)
OPEN_ACCESS_POLICY
Open Access Policy
Creative Commons Attribution-Noncommercial-Share Alike
Terms of use
Metadata
Show full item recordAbstract
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.
Date issued
2014-05Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science; 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; Koch Institute for Integrative Cancer Research at MITJournal
Nature Nanotechnology
Publisher
Nature Publishing Group
Citation
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.
Version: Author's final manuscript
ISSN
1748-3387
1748-3395