Artigo Acesso aberto Revisado por pares

Designed guanidinium-rich amphipathic oligocarbonate molecular transporters complex, deliver and release siRNA in cells

2012; National Academy of Sciences; Volume: 109; Issue: 33 Linguagem: Inglês

10.1073/pnas.1211361109

ISSN

1091-6490

Autores

Erika I. Geihe, Christina B. Cooley, Jeff Simon, Matthew K. Kiesewetter, Justin A. Edward, Robyn P. Hickerson, Roger L. Kaspar, James L. Hedrick, Robert M. Waymouth, Paul A. Wender,

Tópico(s)

Dendrimers and Hyperbranched Polymers

Resumo

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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