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J Med Chem. 2005 Feb 24;48(4):901-4.

Fully 2'-modified oligonucleotide duplexes with improved in vitro potency and stability compared to unmodified small interfering RNA.

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  • 1Department of Medicinal Chemistry, Isis Pharmaceuticals, 2292 Faraday Avenue, Carlsbad, California 92008, USA.


We have identified a small interfering RNA (siRNA) motif, consisting entirely of 2'-O-methyl and 2'-fluoro nucleotides, that displays enhanced plasma stability and increased in vitro potency. At one site, this motif showed remarkable >500-fold improvement in potency over the unmodified siRNA. This marks the first report of such a potent fully modified motif, which may represent a useful design for therapeutic oligonucleotides.

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