Physicochemical convergence in antibody CDR3-VH repertoires recognizing phosphorothioate-modified oligonucleotides backbone - Takeaways - MDSpire

Physicochemical convergence in antibody CDR3-VH repertoires recognizing phosphorothioate-modified oligonucleotides backbone

  • By

  • Riccardo Galasso

  • Francesco Coppolino

  • Alessia Berbiglia

  • Grete Francesca Privitera

  • Agata Famà

  • Giuseppe Valerio De Gaetano

  • Germana Lentini

  • Concetta Beninati

  • May 29, 2026

  • 0 min

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  • 1

    The study investigates antibody binders against phosphorothioate-modified antisense oligonucleotides using next-generation sequencing and phage display.

  • 2

    Deep sequencing revealed reduced repertoire diversity and clonal dominance from Round 1 to Round 2 of selection against PS-ASOs.

  • 3

    A shared set of 113 CDR3-VH clonotypes was identified, displaying increased positive charge and specific physicochemical properties.

  • 4

    The scFv clone 12F2 showed preferential binding to PS-ASOs and produced detectable signals in ASO-treated cells.

  • 5

    The findings suggest that early selection against PS-ASOs leads to reproducible repertoire focusing and physicochemical convergence.

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