Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals
Open accessAbstract
Significance: Protein expression using mRNA has the potential to transform many areas of life science research and affect the prevention, detection, and treatment of disease. However, realizing this potential requires the development of readily accessible, efficacious, and safe delivery systems that can functionally deliver mRNA to cells in culture and in vivo. A class of materials developed for mRNA delivery is described that operates through an unprecedented self-immolation mechanism. These materials are accessed in two steps through an organocatalytic oligomerization. They noncovalently complex, protect, deliver, and release mRNA with >99% transfection efficiency in cultured cells and with robust protein expression in mice using multiple routes of administration. This mRNA delivery technology should be broadly applicable to numerous research and therapeutic applications.
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Charge-altering releasable transporters and modified dendrimers can effectively deliver mRNA molecules in vitro and in vivo.
“In addition, charge-altering releasable transporters162,247 and modified dendrimers248 can effectively deliver mRNA molecules in vitro and in vivo.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [247]
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- Authors
- McKinlay, C. J., Vargas, J. R., Blake, T. R., Hardy, J. W., Kanada, M., Contag, C. H., Wender, P. A., & Waymouth, R. M.
- Affiliations
- Stanford University (US)
- Stanford Medicine (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-01-09
- Volume
- 114
- Issue
- 4
- Pages
- E448-E456
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5278438
- OpenAlex
- W2570278065
- Cited by
- 288
- References
- 61
- Citations by year
- 2026: 18 · 2025: 28 · 2024: 42 · 2023: 45 · 2022: 35 · 2021: 31 · 2020: 30 · 2019: 26 · 2018: 27 · 2017: 6
- FWCI
- 9.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- U.S. Department of Energy (DE-SC0005430)
- National Science Foundation (GOALI CHE-1306730)
- HHS | NIH | National Cancer Institute (NIH-CA031841, NIH-CA031845)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- mRNA delivery, intramolecular rearrangement, mRNA translation, mRNA vaccines, genome editing, protein replacement therapy
- MeSH terms
- Animals, Biocompatible Materials, Carbocyanines, Cell Line, Cells, Cultured, Female, Humans, Mice, Inbred BALB C, RNA, Messenger, Gene Transfer Techniques, Cell Line, Tumor, Green Fluorescent Proteins, Mesenchymal Stem Cells
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