Document Type
Article
Publication Date
8-2012
Abstract
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.
DOI
10.1073/pnas.1211361109
Publisher
National Academy of Sciences
Repository Citation
Geihe, E. I., Cooley, C. B., Simon, J. R., Kiesewetter, M. K., Edward, J. A., Hickerson, R. P., ... Wender, P. A. (2012). Designed guanidinium-rich amphipathic oligocarbonate molecular transporters complex, deliver and release siRNA in cells. PNAS, 109(33), 13171-13176. https://doi.org/10.1073/pnas.1211361109
Publication Information
PNAS