TSHR-Targeting Nucleic Acid Aptamer Treats Graves' Ophthalmopathy via Novel Allosteric Inhibition.

ABSTRACT: Graves' ophthalmopathy (GO) is an autoimmune disorder marked by orbital inflammation and tissue remodeling, leading to irreversible disfigurement and vision loss. The current first-line glucocorticoid therapy remains palliative, underscoring the critical need for mechanism-based interventions. Autoantibodies against thyrotropin receptor (TSHR) in GO patients highlight its therapeutic potential, yet TSHR inhibitor development faces challenges, including low potency, off-target effects, and mechanistic constraints. To overcome this therapeutic void, YC3, a TSHR-targeting nucleic acid aptamer, has been developed through an innovative approach that combines protein-targeting cell-SELEX with functional selection. YC3 exhibits nanomolar affinity alongside robust pharmacodynamic efficacy. In vitr

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12822413 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature