Phosphorothioate (PS) Panels

The Role of PS Modifications in ASO Drug Design

Phosphorothioate (PS) modification is an foundational first-generation modification intended to stabilize oligonucleotide therapeutics against nucleic acid degradation. While the naturally occurring phosphodiester (PO) bond is sensitive to nuclease degradation, the PS internucleosidic linkage offers enhanced resistance to exonuclease degradation. PS modification is commonly incorporated into antisense oligonucleotides (ASO), small interfering RNAs (siRNA), and other RNA modalities to improve stability. ASOs may also be configured as “gapmers”, in which multiple PS residues flank a central DNA core, while siRNA typically feature PS residues at the 5’ and 3’ termini of both sense and antisense strands.

While PS modification enhance stability, too many PS bonds can increase toxicity. Strategies have emerged to use partial PS modification, often in combination with second-generation chemistries such as 2’-MOE, 2’-OMe, 2’-Fl, or LNA to balance potency and safety.

ModDetect™ PS panels contain highly specific antibodies that detect PS bonds independent of nucleic acid sequence. These reagents enable quantitative immunoassays for biodistribution, intracellular localization, quantification, and bioanalytical characterization of PS-modified ASOs, siRNA, miRNA, aptamers, and mRNA, with as few as two non-overlapping epitopes on a PS-modified oligonucleotide needed for detection in a sandwich ELISA.