Synthesis of RNA Dimer and Trimer Blocks and Their Uses

Abstract

Since RNA interference was first observed in plants, worms, and then mammalian cells, siRNA becomes a potent therapeutic approach to cure diseases. However, the synthesis of RNA oligonucleotide usually gives lower purities and yields than DNA oligonucleotides due to 2′- hydroxyl group. To be an affordable medicine, many approaches for higher purities and yields have been attempted in RNA oligoncucleotide synthesis. New RNA phosphoramidites and other types of monomer, solution phase synthesis, hybrid of solid-solution phase synthesis, and novel supports are among them. We have developed an efficient method to synthesize siRNA using RNA dinucleotide blocks in solid phase synthesis. Various RNA dimer phosphoramidites were synthesized and applied for siRNA synthesis giving the highly pure RNA oligonucleotides comparable to DNA oligonucleotides. The RNA trimer blocks were also synthesized and its application will be discussed as well.