Optimized CAG-targeting artificial microRNAs demonstrate high efficacy and specificity in cellular and mouse models of polyglutamine disorders
The aim was to develop a safe and effective therapeutic approach for Huntington's disease (HD) and other polyQ disorders using artificial microRNAs (amiRNAs) targeting CAG repeats. Optimized amiRNAs with two mismatches selectively reduced mutant HTT and other polyQ proteins in cell and animal models without major side effects. The most promising candidate, amiR136-13A, showed high efficacy, allele selectivity, and safety, indicating its potential for future clinical application.strategy.These studies were funded by the project Preludium Bis 1, Allele-selective therapy for polyglutamine diseases with the use of RNA interference technology (2019/35/O/NZ1/03535), funded by National Science Centre, Poland.