GluK2 kainate receptor subunit-selective, potentiating RNA aptamer

Samantha R Ingenito,Noah Saunders,Kyle J. Lininger,Li Niu

Published 2025 in Scientific Reports

ABSTRACT

Kainate receptors are a subtype of ionotropic glutamate receptors. Potent and selective modulatory agents of kainate receptors are potential drug candidates for treatment of various neurological diseases involving receptor dysregulation. Here, we report an RNA aptamer that selectively potentiates GluK2, a key kainate receptor subunit. The potentiating aptamer, termed U9, is designed by changing the sequence of the predecessor RNA, which is an inhibitor without subunit selectivity, leading to the change of function: U9 selectively potentiates GluK2 with an EC50 of ~ 210 nM. Our study demonstrates a potential utility of combining molecular docking with functional assay for a template-based discovery of potent, single-subunit selective RNA aptamers.

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