Key result
Emerging biologics like gene editing show promise in directly correcting congenital long QT syndrome defects.
Why the study?
Current standard-of-care management for congenital LQTS mitigates electrophysiological consequences but does not correct underlying genetic defects, prompting evaluation of emerging biological therapies.
This review provides a comprehensive, mechanism-based framework to inform future precision medicine approaches for congenital long QT syndrome, highlighting the transition from conventional management to emerging biological therapies.
Promising preclinical gene-editing and RNAi strategies in congenital LQTS should not yet change practice; leaves open translational barriers in delivery, off-target effects, and durability.
Congenital long QT syndrome (LQTS), the first identified cardiac ion channelopathy, is characterized by delayed ventricular repolarization and a prolonged heart rate-corrected QT interval (QTc), conferring an increased risk of malignant ventricular arrhythmias and sudden cardiac death. Current standard-of-care management for LQTS, including beta-blockers, sodium channel blockers, left cardiac sympathetic denervation (LCSD), and implantable cardioverter-defibrillators (ICDs), reduces adverse events and improves survival but primarily mitigates downstream electrophysiological consequences rather than correcting the underlying genetic defects. Rapid advances in molecular biology have driven the development of mechanism-directed strategies such as gene editing, RNA interference (RNAi), and experimental antibody-based interventions, which aim to restore channel function or modulate channel regulation at the source. This review synthesizes current knowledge on LQTS classification and pathogenesis and evaluates both guideline-directed therapies and emerging molecular interventions. We emphasize subtype-specific approaches, highlight the rationale and preclinical progress for gene- and RNA-based therapies, and outline practical considerations for translation, including delivery, durability, and safety. Therefore, this review provides a comprehensive, mechanism-based framework to inform future precision medicine approaches for LQTS.
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Liu et al. (2026) conducted a review in Congenital Long QT Syndrome. Biological therapies (gene editing, RNA interference, antibody therapy) vs. Conventional management was evaluated. Emerging biological therapies such as gene editing and RNA interference offer promising mechanism-directed strategies to correct underlying genetic defects in congenital long QT syndrome.
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