Journal of Medicinal Chemistry · 2005 · 442 citations · 36 references
PharmacyChemical BiologyMolecular BiologyGene DeliveryNucleic Acid BiochemistryNucleic Acid ChemistryNucleic Acid DeliveryNucleic Acid Drug DesignOligonucleotide ChemistryRna InterferenceRna ModificationSmall Interfering Rna Biology2'-Fluoro Nucleic Acids2'-O-methyl OligonucleotidesChemical Modification Of OligonucleotidesChemical Modification Of Small Interfering Ribonucleic AcidsChemical Modification Of Small Interfering RnaSmall Interfering Ribonucleic Acids (Sirnas)Small Interfering Rna ModificationsTherapeutic Small Interfering Rna
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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