Polymer–Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs
Abstract
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.
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LPPs have higher stability, low cytotoxicity, cell delivery and endosomal escape efficiency.
“LPPs have higher stability, low cytotoxicity, cell delivery and endosomal escape efficiency.327–329”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [329]
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References 28 · Cited by 60
- Authors
- Kaczmarek, J. C., Patel, A. K., Kauffman, K. J., Fenton, O. S., Webber, M. J., Heartlein, M. W., DeRosa, F., & Anderson, D. G.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- University of Nottingham (GB)
- Shire (United States) (US)
- Harvard University (US)
- Corresponding author
- Anderson, Daniel G.
- Venue
- Angewandte Chemie
- Publisher
- Wiley
- Published
- 2016-09-30
- Volume
- 128
- Issue
- 44
- Pages
- 14012-14016
- ISSN
- 0044-8249 (ISSN-L)
- 1521-3757
- OpenAlex
- W2607675704
- Cited by
- 60
- References
- 28
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 5 · 2023: 7 · 2022: 8 · 2021: 9 · 2020: 4 · 2019: 3 · 2018: 7 · 2017: 2 · 2016: 3
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Angewandte Chemie (publishedVersion)
- Funders
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- Shire
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- mRNA delivery, poly(β-amino ester), systemic drug delivery, pulmonary drug delivery, intravenous administration, serum stability
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