RNA synthesis via dimer and trimer phosphoramidite block coupling

The solid-phase synthesis of oligoribonucleotides using dimer and trimer phosphoramidite blocks is described. This method significantly reduces the total number of steps required in the synthesis of a target RNA sequence, provides more material, and simplifies separation of the product from shorter failure sequences. The procedure is illustrated by the synthesis of UpU, ApA, and UpUpU phosphoramidite blocks and their use in the rapid synthesis of oligoribonucleotides on a solid support. Dimer and trimer amidite blocks will likely find use in the large scale solution (or solid)-phase synthesis of siRNA drugs.