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

Charles R Allerson·Namir Sioufi·Russell Jarres·Thazha P Prakash·Nishant Naik·Andres Berdeja·Lisa Wanders·Richard H Griffey·Eric E Swayze·Balkrishen Bhat
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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.

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AnimalsDrug CarriersDrug StabilityHeLa CellsHumansMiceOligonucleotidesPTEN PhosphohydrolasePhosphatidylethanolaminesPhosphoric Monoester HydrolasesRNA, MessengerRNA, Small InterferingReverse Transcriptase Polymerase Chain ReactionStructure-Activity RelationshipTransfectionTumor Suppressor ProteinsComparative StudyJournal Article

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Charles R Allerson, Namir Sioufi, Russell Jarres, Thazha P Prakash, Nishant Naik, Andres Berdeja, Lisa Wanders, Richard H Griffey, Eric E Swayze, Balkrishen Bhat. 2005-02-24. Fully 2'-modified oligonucleotide duplexes with improved in vitro potency and stability compared to unmodified small interfering RNA.. https://doi.org/10.1021/jm049167j

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