Detritylation step in solid phase oligonucleotide synthesis

Abstract

Aspects of the disclosure relate to methods and systems for solid phase oligonucleotide synthesis (SPOS). In some embodiments, the methods described by the disclosure comprise a step of performing a deblocking step (e.g., a detritylation reaction) during each cycle of the SPOS reaction. In some embodiments, performing the deblocking steps with neat or high concentration DCA addback to the reuse acid solution during deblocking, reuse DCA-rich portion of post-detritylation ACN wash as part of the deblocking process, using the distillation bottoms is used as part of the deblocking process, or deblocking in FBR with thiol scavengers requires a significantly reduced amount of deblocking reagent, such as acid solution, during the entire SPOS process relative to SPOS processes where the deblocking step is carried out at room temperature.

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