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

ABSTRACT: Antibody-small interfering RNA (siRNA) conjugates present an opportunity to expand the siRNA therapy to extrahepatic tissues. However, their investigation is now only confined to a limited number of targets, partially owing to some flaws in structures. Here, we described a modular design of bifunctional antibody that tethers siRNA without conjugation, yielding a diligent one-to-one antibody-siRNA pairing structure feasible for target expansion, charge masking, and further functionalization. Focusing on a noncationic siRNA-recruiting module, Staufen1 dsRBD34, we demonstrated that bifunctional antibodies recruit siRNA independent of base modification and enable target gene silencing on multiple cell types at a stoichiometry (1/1). Notably, by functionalizing siRNA terminus with small-molecul

SUBMITTER: Liu Y 

PROVIDER: S-EPMC12825305 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature