1. Designed guanidinium-rich amphipathic oligocarbonate molecular transporters complex, deliver and release siRNA in cells.
- Author
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Geihe EI, Cooley CB, Simon JR, Kiesewetter MK, Edward JA, Hickerson RP, Kaspar RL, Hedrick JL, Waymouth RM, and Wender PA
- Subjects
- Biological Transport drug effects, Carbonates chemical synthesis, Carbonates toxicity, Cell Death drug effects, Cells, Cultured, Flow Cytometry, Gene Transfer Techniques, Genes, Reporter genetics, Green Fluorescent Proteins metabolism, Guanidine chemical synthesis, Guanidine toxicity, Humans, Keratinocytes cytology, Keratinocytes drug effects, Light, Solanum lycopersicum metabolism, Microscopy, Fluorescence, RNA, Small Interfering toxicity, Scattering, Radiation, Carbonates chemistry, Guanidine chemistry, Keratinocytes metabolism, RNA, Small Interfering metabolism
- 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.
- Published
- 2012
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