Recent advances in the chemical synthesis of RNA

As a consequence largely of recent developments in RNA interference (RNAi) research, the availability of rapid and efficient methods for the chemical synthesis of RNA sequences has become a matter of considerable urgency. This unit is concerned mainly with work that has been carried out, especially in the past decade, on the design of new and improved methods of RNA synthesis. The main criteria for the choice of protecting groups for the 2'-hydroxy functions of the ribonucleoside building blocks, which is arguably the most crucial strategic decision to be made, are discussed. A number of new ether-, acetal-, orthoester-, and ester-based 2'-protecting groups are described and their application, mainly in phosphoramidite-based solid-phase synthesis, is discussed in some detail. Brief consideration is also given to solution-phase RNA synthesis, which may well prove to be of great importance if a systemic drug is developed and multikilogram quantities of synthetic RNA sequences are required.