TIDES USA 2025: Comparative Analysis of Diastereomeric Distribution in siRNA Synthesis: Phosphoramidite Chemistry vs Enzymatic Synthesis

This study compares the diastereomeric profiles of siRNA oligonucleotides synthesized using traditional phosphoramidite chemistry and the Enzyme Catalyzed Oligo (ECO) Synthesis™ platform, which employs 3′-phosphate blocked ribonucleotides (NQPs). We examine how phosphorothioate (PS) modifications—and their positions within the oligonucleotide sequence—influence the resulting diastereomeric composition in siRNA produced by both methods.

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