Abstract
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.
MeSH terms
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Animals
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Drug Carriers
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Drug Stability
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HeLa Cells
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Humans
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Mice
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Oligonucleotides / chemical synthesis*
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Oligonucleotides / chemistry
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Oligonucleotides / pharmacology
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PTEN Phosphohydrolase
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Phosphatidylethanolamines
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Phosphoric Monoester Hydrolases / biosynthesis
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Phosphoric Monoester Hydrolases / genetics*
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RNA, Messenger / biosynthesis
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RNA, Messenger / chemistry*
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RNA, Small Interfering / chemistry*
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RNA, Small Interfering / genetics
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Reverse Transcriptase Polymerase Chain Reaction
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Structure-Activity Relationship
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Transfection
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Tumor Suppressor Proteins / biosynthesis
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Tumor Suppressor Proteins / genetics*
Substances
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Drug Carriers
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Oligonucleotides
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Phosphatidylethanolamines
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RNA, Messenger
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RNA, Small Interfering
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Tumor Suppressor Proteins
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1,2-dielaidoylphosphatidylethanolamine
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Phosphoric Monoester Hydrolases
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PTEN Phosphohydrolase
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PTEN protein, human