Fully 2‘-Modified Oligonucleotide Duplexes with Improved in Vitro Potency and Stability Compared to Unmodified 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. Thi...

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Veröffentlicht in:	Journal of medicinal chemistry 2005-02, Vol.48 (4), p.901-904
Hauptverfasser:	Allerson, Charles R, Sioufi, Namir, Jarres, Russell, Prakash, Thazha P, Naik, Nishant, Berdeja, Andres, Wanders, Lisa, Griffey, Richard H, Swayze, Eric E, Bhat, Balkrishen
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Biological and medical sciences Biotechnology Drug Carriers Drug Stability Fundamental and applied biological sciences. Psychology Gene therapy Health. Pharmaceutical industry HeLa Cells Humans Industrial applications and implications. Economical aspects Medical sciences Mice Miscellaneous Oligonucleotides - chemical synthesis Oligonucleotides - chemistry Oligonucleotides - pharmacology Pharmacology. Drug treatments Phosphatidylethanolamines Phosphoric Monoester Hydrolases - biosynthesis Phosphoric Monoester Hydrolases - genetics PTEN Phosphohydrolase Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - biosynthesis RNA, Messenger - chemistry RNA, Small Interfering - chemistry RNA, Small Interfering - genetics Structure-Activity Relationship Transfection Tumor Suppressor Proteins - biosynthesis Tumor Suppressor Proteins - genetics
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Zusammenfassung:	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.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm049167j