1. In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight
- Author
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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 MIT, 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, Khan, Omar Fizal, Bogorad, Roman, Ruda, Vera, Langer, Robert S, 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 MIT, 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, Khan, Omar Fizal, Bogorad, Roman, Ruda, Vera, and Langer, Robert S
- Abstract
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., American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowship, National Science Foundation (U.S.), Massachusetts Institute of Technology. Presidential Fellowship
- Published
- 2016