Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 33, Pages 13171-13176Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1211361109
Keywords
amphipathic co-oligomers; nanoparticles; oligonucleotide delivery; biodegradable oligomers; organocatalysis
Categories
Funding
- National Science Foundation [NSF-CHE-0957386, RC2AR058955]
- National Institutes of Health [NIH-CA31841, NIH-CA31845]
- National Science Foundation
- Stanford Graduate Fellowship
- IBM
- Division Of Chemistry
- Direct For Mathematical & Physical Scien [0957386] Funding Source: National Science Foundation
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The polyanionic nature of oligonucleotides and their enzymatic degradation present challenges for the use of siRNA in research and therapy; among the most notable of these is clinically relevant delivery into cells. To address this problem, we designed and synthesized the first members of a new class of guanidinium-rich amphipathic oligocarbonates that noncovalently complex, deliver, and release siRNA in cells, resulting in robust knockdown of target protein synthesis in vitro as determined using a dual-reporter system. The organocatalytic oligomerization used to synthesize these co-oligomers is step-economical and broadly tunable, affording an exceptionally quick strategy to explore chemical space for optimal siRNA delivery in varied applications. The speed and versatility of this approach and the biodegradability of the designed agents make this an attractive strategy for biological tool development, imaging, diagnostics, and therapeutic applications.
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