Patient-specific, re-engineered cardiomyocyte model confirms the circumstance-dependent arrhythmia risk associated with the African-specific common SCN5A polymorphism p.S1103Y: Implications for the increased sudden deaths observed in black individuals during the COVID-19 pandemic

Abstract

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Deciphering Common Long QT Syndrome Using CRISPR/Cas9 in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes

“…CRISPR/Cas9 generation knockdown of SCN5A to generate the Nav1.5 KO hiPSC lineage or the introduction of pathogenic mutations to build control models has great breakthroughs in analyzing the pathophysiological mechanisms of the phenotype (15,105,106). Similarly, drug arrhythmogenic susceptibility can be determined using genomically corrected SCN5A variant isogenic control cell lines (105).…”

“…CRISPR/Cas9 generation knockdown of SCN5A to generate the Nav1.5 KO hiPSC lineage or the introduction of pathogenic mutations to build control models has great breakthroughs in analyzing the pathophysiological mechanisms of the phenotype (15,105,106). Similarly, drug arrhythmogenic susceptibility can be determined using genomically corrected SCN5A variant isogenic control cell lines (105). Even introducing CRISPR/Cas9 in hiPSCs makes it possible to compare the properties of different variants, a single variant in different cell models, or even differences between homozygous or heterozygous mutation (107,143).…”