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January 24, 2026

Staufen dsRNA-binding domain as modules to design bifunctional antibodies for siRNA delivery.

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Authors

YLYing LiuYZYan ZhengRXRuolin Xu

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Overview

Research demonstrates enhanced siRNA delivery with bifunctional antibodies in various cell types, indicating potential for broader therapeutic use.

Key Points

  • This research aims to develop bifunctional antibodies that effectively deliver siRNA for gene silencing in extrahepatic tissues.
  • Designed bifunctional antibodies with Staufen1 dsRBD34 for siRNA recruitment.
  • Tested the siRNA-antibody pairing across multiple cell types for target gene silencing.
  • Conducted affinity maturation via arginine scanning to enhance dsRNA-binding affinity.
  • Assessed silencing potency changes with small-molecule enhancers.
  • Evaluated pharmacokinetics of paired systems in circulation.
  • Achieved 1:1 stoichiometry in siRNA-antibody pairing.
  • Increased silencing potency of siRNA by seven times with terminal enhancements (IC50 reduced from 200 to 28 nM).
  • Affinity maturation resulted in a 32-fold increase in binding affinity to siRNA.
  • Sulfated GAGs significantly affected pharmacokinetics, complicating in vivo assessments.
  • Bifunctional antibodies demonstrated potential but required ultrahigh-affinity domains for practical application.

Cite This Study

Liu et al. (2026) studied this question.

synapsesocial.com/papers/6974616cbb9d90c67120b4adhttps://doi.org/10.1093/nar/gkaf1539
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