Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs
Therapeutic nucleic acids hold great promise for the treatment of disease but require vectors for safe and effective delivery. Synthetic nanoparticle vectors composed of poly(β-amino esters) (PBAEs) and nucleic acids have previously demonstrated potential utility for local delivery applications. To...
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| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2017
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| Online Access: | http://hdl.handle.net/1721.1/107933 https://orcid.org/0000-0002-6516-7499 https://orcid.org/0000-0002-7266-9251 https://orcid.org/0000-0002-9436-2453 https://orcid.org/0000-0002-5585-9280 https://orcid.org/0000-0003-0624-3532 https://orcid.org/0000-0001-5629-4798 |
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| author | Heartlein, Michael W. DeRosa, Frank Kaczmarek, James Cliff Kauffman, Kevin John Webber, Matthew Anderson, Daniel Griffith Patel, Asha Fenton, Owen Shea |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Heartlein, Michael W. DeRosa, Frank Kaczmarek, James Cliff Kauffman, Kevin John Webber, Matthew Anderson, Daniel Griffith Patel, Asha Fenton, Owen Shea |
| author_sort | Heartlein, Michael W. |
| collection | MIT |
| description | Therapeutic nucleic acids hold great promise for the treatment of disease but require vectors for safe and effective delivery. Synthetic nanoparticle vectors composed of poly(β-amino esters) (PBAEs) and nucleic acids have previously demonstrated potential utility for local delivery applications. To expand this potential utility to include systemic delivery of mRNA, hybrid polymer–lipid nanoformulations for systemic delivery to the lungs were developed. Through coformulation of PBAEs with lipid–polyethylene glycol (PEG), mRNA formulations were developed with increased serum stability and increased in vitro potency. The formulations were capable of functional delivery of mRNA to the lungs after intravenous administration in mice. To our knowledge, this is the first report of the systemic administration of mRNA for delivery to the lungs using degradable polymer–lipid nanoparticles. |
| first_indexed | 2024-09-23T13:50:50Z |
| format | Article |
| id | mit-1721.1/107933 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:50:50Z |
| publishDate | 2017 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/1079332022-09-28T16:36:28Z Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs Heartlein, Michael W. DeRosa, Frank Kaczmarek, James Cliff Kauffman, Kevin John Webber, Matthew Anderson, Daniel Griffith Patel, Asha Fenton, Owen Shea Massachusetts Institute of Technology. Institute for Medical Engineering & Science Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Chemistry Koch Institute for Integrative Cancer Research at MIT Kaczmarek, James Cliff Patel, Asha K Kauffman, Kevin John Fenton, Owen S. Webber, Matthew Anderson, Daniel Griffith Therapeutic nucleic acids hold great promise for the treatment of disease but require vectors for safe and effective delivery. Synthetic nanoparticle vectors composed of poly(β-amino esters) (PBAEs) and nucleic acids have previously demonstrated potential utility for local delivery applications. To expand this potential utility to include systemic delivery of mRNA, hybrid polymer–lipid nanoformulations for systemic delivery to the lungs were developed. Through coformulation of PBAEs with lipid–polyethylene glycol (PEG), mRNA formulations were developed with increased serum stability and increased in vitro potency. The formulations were capable of functional delivery of mRNA to the lungs after intravenous administration in mice. To our knowledge, this is the first report of the systemic administration of mRNA for delivery to the lungs using degradable polymer–lipid nanoparticles. Shire Pharmaceuticals MIT Skoltech Initiative National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051) 2017-04-07T15:18:02Z 2017-04-07T15:18:02Z 2016-09 2016-09 Article http://purl.org/eprint/type/JournalArticle 1433-7851 1521-3773 http://hdl.handle.net/1721.1/107933 Kaczmarek, James C. et al. “Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs.” Angewandte Chemie International Edition 55.44 (2016): 13808–13812. https://orcid.org/0000-0002-6516-7499 https://orcid.org/0000-0002-7266-9251 https://orcid.org/0000-0002-9436-2453 https://orcid.org/0000-0002-5585-9280 https://orcid.org/0000-0003-0624-3532 https://orcid.org/0000-0001-5629-4798 en_US http://dx.doi.org/10.1002/anie.201608450 Angewandte Chemie International Edition Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Blackwell PMC |
| spellingShingle | Heartlein, Michael W. DeRosa, Frank Kaczmarek, James Cliff Kauffman, Kevin John Webber, Matthew Anderson, Daniel Griffith Patel, Asha Fenton, Owen Shea Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs |
| title | Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs |
| title_full | Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs |
| title_fullStr | Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs |
| title_full_unstemmed | Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs |
| title_short | Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs |
| title_sort | polymer lipid nanoparticles for systemic delivery of mrna to the lungs |
| url | http://hdl.handle.net/1721.1/107933 https://orcid.org/0000-0002-6516-7499 https://orcid.org/0000-0002-7266-9251 https://orcid.org/0000-0002-9436-2453 https://orcid.org/0000-0002-5585-9280 https://orcid.org/0000-0003-0624-3532 https://orcid.org/0000-0001-5629-4798 |
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