In order for the SoM based method to be suitable for the synthesis of sensitive RNAs such as ac4C-RNAs, a linker that can be cleaved under mild non-nucleophilic conditions is required. In the literature, this was usually achieved using UV-cleavable 2-nitrobenzyl linkers. We used oxidatively cleavable Dmoc linker for the purpose, but only DNA synthesis has been demonstrated so far. For the SoM based sensitive RNA synthesis method, we designed the SoA linker, the structure of which is illustrated in 1f (Figure ). The mechanism for linker cleavage is similar to that for the deprotection of SoM groups. Removal of the TBS group in SoA with fluoride exposes the hydroxy group, which attacks the ester intramolecularly to release the RNA. Formation of a 5-membered lactone provides the driving force for the reaction to proceed under neutral conditions. The phosphate group (pKa of H2PO4 -, 7.2) as illustrated in 3 (Scheme 1) was expected to provide even stronger electron-withdrawing effect than the methoxy group (pKa of MeOH, 15.5) in SoM for the lactonization reaction to occur, which is predictable based on related pKa values. Compared with UV-cleavable linkers as well as other linkers, the SoA linker has the advantage of cleavage at the same time as the deprotection of 2′-OTBS and exo-amino SoM groups. In addition, using SoA linker, there is no concern for RNA damage by UV or oxidation.