Compared to DNA synthesis, RNA production is more complex. In standard DNA synthesis, all nucleophilic functions are protected with base-labile protecting groups, removed at the end of the elongation process with a base treatment. But the main hurdle with RNA chemistry results from the well-established RNA instability in basic media. Thus to avoid the 2’-OH nucleophilic attack on the P-atom of the internucleoside linkage, the 2’-OH protection musn’t be base-labile.

Nowadays, 2’-OH protections, commonly used to synthesize RNA oligonucleotides, require a deprotection step with fluoride ions and time-consuming purification steps, for example : TBDMS group (Tert-ButylDiMethylSilyl), TOM group (Triisopropylsilyloxymethyl), CEM group (2-CyanoEthoxyMethyl), TEM group (ToluylsulfonylEthoxyMethyl)…

Many research laboratories, all over the world, have been working on this 2’-O-protection problem to improve RNA quality, purity, and synthesis process. Several alternative protecting groups have been tested but to date, none of them has been able to replace the widely used TBDMS protection for RNA production.