Stabilizer Cell Gene Therapy
Year: 2020
Type: article
Abstract: BACKGROUND: In cardiac gene therapy to improve contractile function, achieving gene expression in the majority of cardiac myocytes is essential. In preventing cardiac arrhythmias, however, this goal may not be as important since transduction efficiencies as low as 40% suppressed ventricular arrhythmias in genetically modified mice with catecholaminergic polymorphic ventricular tachycardia. METHODS: Using computational modeling, we simulated 1-, 2-, and 3-dimensional tissue under a variety of conditions to test the ability of genetically engineered nonarrhythmogenic stabilizer cells to suppress triggered activity due to delayed or early afterdepolarizations. RESULTS: Due to source-sink relationships in cardiac tissue, a minority (20%-50%) of randomly distributed stabilizer cells engineered to be nonarrhythmogenic can suppress the ability of arrhythmogenic cells to generate delayed and early afterdepolarizations-related arrhythmias. Stabilizer cell gene therapy strategy can be designed to correct a specific arrhythmogenic mutation, as in the catecholaminergic polymorphic ventricular tachycardia mice studies, or more generally to suppress delayed or early afterdepolarizations from any cause by overexpressing the inward rectifier K channel Kir2.1 in stabilizer cells. CONCLUSIONS: This promising antiarrhythmic strategy warrants further testing in experimental models to evaluate its clinical potential.
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Afterdepolarizations and Cardiac Arrhythmias, A population-based in silico platform for arrhythmia prediction, Triggered arrhythmias induced by heart failure remodeling: A multi-scale computational approach, UCLA-Caltech Medical Scientist Training Program, KITP Interdisciplinary Biology Initiative, Cardiac Fibrillation: Mechanisms and Therapy
OpenAlex ID: W3044012237