In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight
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....
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| Format: | Article |
| Language: | en_US |
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Nature Publishing Group
2016
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| Online Access: | http://hdl.handle.net/1721.1/101130 https://orcid.org/0000-0002-2100-1171 https://orcid.org/0000-0001-5786-0659 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0001-6898-3793 https://orcid.org/0000-0003-3811-2369 https://orcid.org/0000-0001-8223-035X https://orcid.org/0000-0003-0624-3532 https://orcid.org/0000-0001-8046-2288 https://orcid.org/0000-0003-4255-0492 |
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| author | 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 |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science 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 |
| author_sort | Dahlman, James E. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:05:50Z |
| format | Article |
| id | mit-1721.1/101130 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:05:50Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1011302022-09-30T07:29:48Z In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight 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 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 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 2016-02-09T15:35:33Z 2016-02-09T15:35:33Z 2014-05 2013-08 Article http://purl.org/eprint/type/JournalArticle 1748-3387 1748-3395 http://hdl.handle.net/1721.1/101130 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. https://orcid.org/0000-0002-2100-1171 https://orcid.org/0000-0001-5786-0659 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0001-6898-3793 https://orcid.org/0000-0003-3811-2369 https://orcid.org/0000-0001-8223-035X https://orcid.org/0000-0003-0624-3532 https://orcid.org/0000-0001-8046-2288 https://orcid.org/0000-0003-4255-0492 en_US http://dx.doi.org/10.1038/nnano.2014.84 Nature Nanotechnology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | 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 In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight |
| title | In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight |
| title_full | In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight |
| title_fullStr | In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight |
| title_full_unstemmed | In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight |
| title_short | In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight |
| title_sort | in vivo endothelial sirna delivery using polymeric nanoparticles with low molecular weight |
| url | http://hdl.handle.net/1721.1/101130 https://orcid.org/0000-0002-2100-1171 https://orcid.org/0000-0001-5786-0659 https://orcid.org/0000-0001-5629-4798 https://orcid.org/0000-0001-6898-3793 https://orcid.org/0000-0003-3811-2369 https://orcid.org/0000-0001-8223-035X https://orcid.org/0000-0003-0624-3532 https://orcid.org/0000-0001-8046-2288 https://orcid.org/0000-0003-4255-0492 |
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