Systemic mRNA delivery to the lungs by functional polyester-based carriers
Abstract
Messenger RNA (mRNA) has recently come into focus as an emerging therapeutic class with great potential for protein replacement therapy, cancer immunotherapy, regenerative medicine, vaccines, and gene editing. However, the lack of effective and safe delivery methods impedes the broad application of mRNA-based therapeutics. We report a robust approach to develop efficient polymeric delivery carriers for mRNA. Lead polyesters were identified by in vitro screening of a 480-member combinatorially modified poly(trimethylolpropane allyl ether-co-suberoyl chloride) library for the delivery of luciferase encoding mRNA (Luc mRNA) to IGROV1 cells. The formulation of mRNA polyplex nanoparticles (NPs) with Pluronic F127 decreased the surface charge. Although this improved the stability of mRNA nanoparticles, the delivery potency decreased with increased F127 content. Thus, we determined that NP stabilization with 5% F127 could balance the protective effects and delivery potency. 5% F127 formulated PE4K-A17-0.33C12 mRNA NPs enabled luciferase expression predominantly in the lungs after intravenous injection into mice. The efficient mRNA delivery specifically to lungs by degradable carriers suggests the potential for the treatment of pulmonary diseases.
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PE4K-A17-0.33C12 nanoparticles formulated with 5% pluronic F127 resulted in obvious luciferase expression in the lungs after systemic administration in mice.
“The PE4K-A17–0.33C12 nanoparticles formulated with 5% pluronic F127 resulted in obvious luciferase expression in the lungs after systematic administration in mice.[195]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [195]
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- Authors
- Yan, Y., Xiong, H., Zhang, X., Cheng, Q., & Siegwart, D. J.
- Affiliations
- Harold C. Simmons Comprehensive Cancer Center (US)
- Corresponding author
- Yan, Yunfeng
- Siegwart, Daniel J.
- Venue
- Biomacromolecules
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-11-27
- Volume
- 18
- Issue
- 12
- Pages
- 4307-4315
- ISSN
- 1525-7797 (ISSN-L)
- 1526-4602
- OpenAlex
- W2770318482
- Cited by
- 111
- References
- 64
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 19 · 2023: 18 · 2022: 12 · 2021: 13 · 2020: 10 · 2019: 6 · 2018: 15
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomacromolecules (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Welch Foundation (I-1855)
- Cancer Prevention and Research Institute of Texas (R1212)
- American Cancer Society (RSG-17-012-01)
- Mary Kay Foundation (049-15)
- Zhejiang University of Technology (105008529)
- 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, pulmonary drug delivery, polyester nanoparticles, Pluronic F127, polymeric carriers, luciferase expression, intravenous injection, lung disease, surface charge, nanoparticle stability
- MeSH terms
- Animals, Drug Carriers, Humans, Lung, Polyesters, Polymers, RNA, Messenger, Mice, SCID, Mice, Inbred NOD, Poloxamer, Cell Line, Tumor, Mice, Nanoparticles
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