Authors
Joschua Geuter, Thomas T Austin, Jack Corke, Naxi Tian, Jordan Brown, Stephanie Schorge, Gareth Morris
Published in
Molecular therapy. Nucleic acids. Volume 37. Issue 3. Pages 103055. Sep 08, 2026. Epub Aug 10, 2026.
Abstract
Gene therapy offers the potential for long-term treatment of a range of chronic diseases. However, permanent gene therapy expression may not be desirable. Efforts have been made to create systems that can be switched on/off by stimuli including light, designer drugs, or cellular contexts including increased electrical activity. Here, we designed a plasmid system in which ion channel expression and function are regulated by microRNA (miR)-an endogenous class of short noncoding RNAs which negatively regulate gene expression. We modified an existing voltage-gated potassium channel gene therapy with a binding cassette for miR-193a-3p, and transfected this "miR-193-OFF" system in neuro2A cells. Co-transfection with an inhibitor or mimic of miR-193a-3p, respectively, enhanced or repressed expression of our transgene, assessed using a GFP marker. Using whole-cell voltage clamp, we observed tuneable voltage-gated potassium currents in cells co-transfected with a miR-193a-3p inhibitor/mimic, compared with a non-targeting control oligonucleotide. Together, this demonstrates the concept of a miR-mediated molecular switch which can bias therapeutic ion channel expression based on a specific miR signal. As miRs are a ubiquitous molecular mechanism, our approach could be applied to a wide range of cellular and disease contexts, potentially expanding gene therapy to new patient populations.
PMID:
42668707
Bibliographic data and abstract were imported from PubMed on 30 Aug 2026.
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