Journal of Medicinal Chemistry · 2005 · 440 citations · 36 references
Vitro PotencyStability ComparedSmall Interfering RnaEngineeringNatural SciencesNucleic Acid BiochemistryOligonucleotideDna ReplicationMolecular BiologyPlasma StabilityAntisense TherapySmall RnaSystems BiologyOligonucleotide DuplexesGenome EditingBiomolecular Engineering
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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Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
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