Solid-phase synthesis of siRNA oligonucleotides.
Since the discovery of RNA interference (RNAi) as a means to silence the expression of specific genes, small interfering RNA (siRNA) oligonucleotides have been recognized as powerful tools for targeting therapeutically important mRNAs and eliciting their destruction. This discovery has created a high demand for synthetic oligoribonucleotides as potential therapeutics and has spurred a renaissance in the development of rapid, efficient methods for solid-phase RNA synthesis. The design and implementation of 2'-hydroxyl protecting groups that provide ribonucleoside phosphoramidites with coupling kinetics and coupling efficiencies comparable to those of deoxyribonucleoside phosphoramidites are key to the production of RNA oligonucleotides in sufficient quantity and purity for pharmaceutical applications. In this context, various siRNAs were chemically modified to identify the biophysical and biochemical parameters necessary for effective and stable RNAi-mediated gene-silencing activities.
Beaucage
Serge L
SL
Division of Therapeutic Proteins, Center for Drug Evaluation and Research, Food & Drug Administration, 8800 Rockville Pike, Bethesda, MD 20892, USA. serge.beaucage@fda.hhs.gov
D000818:Animals; D006801:Humans; D007202:Indicators and Reagents; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000138:chemical synthesis* / Q000494:pharmacology
D007202:Indicators and Reagents; D009841:Oligonucleotides; D034741:RNA, Small Interfering