Chemical synthesis of 2'-O-alkylated siRNAs.
Chemical synthesis has been a major endeavor to create active siRNAs. The downregulation of mRNA by 21-mer double-stranded siRNAs can be improved by using modified nucleotides, especially 2'-O-alkylated ones. Besides the commercially available 2 cent-O-methyl ribosides, 2'-alkyl groups bearing positive charges are especially promising candidates. We have shown that in a proper formulation they are superior to unmodified siRNAs. This may be due to enhanced stability and most probably to a better uptake into the cells.
Engels
Joachim W
JW
Institute of Organic Chemistry and Chemical Biology, J.W. Goethe-Universität, Frankfurt am Main, Germany.
Odadzic
Dalibor
D
Smicius
Romualdas
R
Haas
Jens
J
D000478:Alkylation; D002851:Chromatography, High Pressure Liquid; D015536:Down-Regulation; D013058:Mass Spectrometry; D009943:Organophosphorus Compounds / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*
D009943:Organophosphorus Compounds; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C434331:phosphoramidite