Journal
NATURE NANOTECHNOLOGY
Volume 9, Issue 8, Pages 648-655Publisher
NATURE PORTFOLIO
DOI: 10.1038/NNANO.2014.84
Keywords
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Funding
- National Defense Science and Engineering (NDSEG)
- National Science Foundation (NSF)
- MIT Presidential Fellowships
- Stop and Shop Pediatric Brain Tumour Fund
- Pediatric Brain Tumour Fund
- Deutsche Forschungsgemeinschaft [SA1668/2-1]
- Alnylam
- Center for RNA Therapeutics and Biology
- [R01 CA148663]
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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.
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