期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 4, 页码 E448-E456出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1614193114
关键词
cell-penetrating; gene therapy; nanoparticle; organocatalysis; stimuli-responsive
资金
- Department of Energy [DE-SC0005430]
- National Science Foundation [NSF CHE-1306730]
- NIH [NIH-CA031841, NIH-CA031845]
- Stanford Center for Molecular Analysis and Design
- National Science Foundation
- NIH S10 Shared Instrument Grant [S10RR027431-01]
- National Center for Research Resources [1S10OD010580]
- Chambers Family Foundation for Excellence in Pediatric Research
- Child Health Research Institute at Stanford University
- Direct For Mathematical & Physical Scien
- Division Of Chemistry [1306730] Funding Source: National Science Foundation
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [1607092] Funding Source: National Science Foundation
- U.S. Department of Energy (DOE) [DE-SC0005430] Funding Source: U.S. Department of Energy (DOE)
Functional delivery of mRNA to tissues in the body is key to implementing fundamentally new and potentially transformative strategies for vaccination, protein replacement therapy, and genome editing, collectively affecting approaches for the prevention, detection, and treatment of disease. Broadly applicable tools for the efficient delivery of mRNA into cultured cells would advance many areas of research, and effective and safe in vivo mRNA delivery could fundamentally transform clinical practice. Here we report the step-economical synthesis and evaluation of a tunable and effective class of synthetic biodegradable materials: charge-altering releasable transporters (CARTs) for mRNA delivery into cells. CARTs are structurally unique and operate through an unprecedented mechanism, serving initially as oligo(a-amino ester) cations that complex, protect, and deliver mRNA and then change physical properties through a degradative, charge-neutralizing intramolecular rearrangement, leading to intracellular release of functional mRNA and highly efficient protein translation. With demonstrated utility in both cultured cells and animals, this mRNA delivery technology should be broadly applicable to numerous research and therapeutic applications.
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