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GluK2 kainate receptor subunit-selective, potentiating RNA aptamer.

Samantha R Ingenito¹, Noah Saunders¹, Kyle J Lininger¹

¹Department of Chemistry, Center for Neuroscience Research and RNA Institute, University at Albany, State University of New York, Albany, NY, 12222, USA.

Scientific Reports

|September 11, 2025

Summary

This summary is machine-generated.

Researchers developed a novel RNA aptamer, U9, that selectively enhances the function of the GluK2 kainate receptor subunit. This discovery offers a promising avenue for developing targeted therapeutics for neurological disorders.

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Area of Science:

Neuroscience
Molecular Biology
Drug Discovery

Background:

Kainate receptors are ionotropic glutamate receptors crucial for neurological function.
Dysregulation of kainate receptors is implicated in various neurological diseases.
Selective modulators of kainate receptors are sought as potential therapeutic agents.

Purpose of the Study:

To discover potent and subunit-selective modulatory agents for kainate receptors.
To engineer an RNA aptamer with enhanced selectivity for the GluK2 subunit.
To explore the combination of molecular docking and functional assays for aptamer discovery.

Main Methods:

Design and synthesis of RNA aptamers targeting kainate receptors.
Modification of a non-selective inhibitor RNA to create a potentiator.
Utilizing molecular docking simulations to guide aptamer design.
Functional assays to evaluate aptamer potency and subunit selectivity.

Main Results:

An RNA aptamer, U9, was engineered to selectively potentiate the GluK2 kainate receptor subunit.
U9 demonstrated potentiation with an EC50 of approximately 210 nM.
The study successfully demonstrated a template-based approach for discovering selective RNA aptamers.

Conclusions:

The U9 aptamer represents a potent and selective potentiator of the GluK2 subunit.
This work highlights the utility of integrating computational and experimental methods for aptamer engineering.
The findings provide a foundation for developing novel therapeutics targeting specific kainate receptor subunits.