Optimization of Automated Synthesis of Amide-Linked RNA.

ABSTRACT: The recent FDA approval of several antisense and siRNA drugs illustrates the utility of nucleic acid chemical modifications, but numerous challenges remain for generalized nucleic acid therapeutics, urging the exploration of new modification strategies. Replacing backbone phosphates with amides has shown promise for enhancing siRNA activity, specificity, and nuclease resistance; however, amide-linked RNA has not been fully explored due to lengthy and low yielding manual amide coupling procedures. We have addressed this by automating the assembly of amide-linked RNA using an Expedite 8909 nucleic acid synthesizer and optimizing solid-phase synthesis conditions to achieve 91-95% yields in just 5 min of coupling time. The optimized protocol allowed synthesis of a 21-nucleotide-long siRNA guid

SUBMITTER: Viel JA 

PROVIDER: S-EPMC9201902 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature