Genetic animal model of Long QT Syndrome Type-2 (LQT2) reproduces the neuro-cardiac pathologies and high risk of sudden death seen in people with LQT2, and provides a platform for advanced research and drug testing.
Long QT Syndrome Type-2 (LQT2) is due to genetic variants in the Kcnh2 gene, which encodes a potassium channel protein that is critical for normal electrical function in both the brain and heart. People with LQT2 exhibit cardiac (electrocardiogram, ECG) and neuronal (electroencephalogram, EEG) electrical abnormalities, arrhythmias, seizures, and sudden death (sudden cardiac death and sudden unexpected death in epilepsy, SUDEP). Existing models do not fully reproduce the clinical pathologies seen in people with LQT2. This limits the translational relevance of results from pre-existing models.
The technology consists of three mutant rabbit lines, each with different CRISPR-Cas9-mediated loss-of-function frameshift deletions in the endogenous rabbit Kcnh2 gene (Singh V. et al. J. Transl. Med. 2025, PMC12001650). The CRISPR-Cas9 approach allows for genetic modifications and disease modeling. Rabbits serve as a valuable model species for translational research. In contrast to rodents, cardiac electrical function is very similar in humans and rabbits. The LQT2 rabbits serve as highly clinically relevant models for studying disease progression and treatment response. The genetic model of LQT2 facilitates translational research studies to investigate the prevalence, risk, and mechanisms for neuro-cardiac electrical disturbances and sudden death in LQT2. Mutant rabbits reproduce the clinical phenotype seen in people with LQT2. The models facilitate comprehensive studies to assess the efficacy and safety of therapeutics in LQT2.
Photo for reference only, not a depiction of the invention.
• Genetically precise models created using CRISPR-Cas9 technology for accurate disease simulation.
• Use of rabbits, offering physiological relevance closer to humans compared to smaller animal models.
• Enables targeted study of Kcnh2 gene mutations and their direct impact on EEG and ECG abnormalities, arrhythmias, seizures, and sudden death seen in people with LQT2.
• Facilitates drug efficacy and safety testing, with improved predictive outcomes for human clinical responses.
• Supports accelerated research and development of treatments addressing complex neurological and cardiac disorders.
• Use in academic and pharmaceutical research to improve understanding of cardiac and neurological diseases.
• Investigation of the molecular and physiological effects of Kcnh2 mutations in disease progression in LQT2.
• Support for regulatory and safety assessments of novel drug candidates affecting cardiac and neurological function.
• Development of novel pharmacological and device therapies.
• Preclinical testing of the efficacy of novel and existing anti-arrhythmic and anti-seizure medications.
• Assess the safety of drugs in an animal model at an increased risk of arrhythmias, seizures, and sudden death.
Patent pending
This technology is at approximately TRL 4–5, as the genetically engineered rabbit models have been successfully developed and demonstrated in a controlled laboratory setting with early validation of their relevance to Kcnh2-related disease phenotypes. Further characterization and broader preclinical testing will strengthen their readiness for widespread use in drug development and translational research.
This technology is available for licensing.