Genome Editing and Cardiac Arrhythmias

Abstract

This article reviews progress in the field of cardiac genome editing, in particular, its potential utility in treating cardiac arrhythmias. First, we discuss genome editing methods by which DNA can be disrupted, inserted, deleted, or corrected in cardiomyocytes. Second, we provide an overview of in vivo genome editing in preclinical models of heritable and acquired arrhythmias. Third, we discuss recent advancements in cardiac gene transfer, including delivery methods, gene expression optimization, and potential adverse effects associated with therapeutic somatic genome editing. While genome editing for cardiac arrhythmias is still in its infancy, this approach holds great promise, especially for inherited arrhythmia syndromes with a defined genetic defect.

Long-term efficacy and safety of cardiac genome editing for catecholaminergic polymorphic ventricular tachycardia

“…Picrosirius staining revealed similar, low levels of fibrosis in the hearts of WT, R176Q/+ control, and R176Q/+ gRNA-Cas9 treated mice [Figure 6A and B]. Because AAV9 is known to accumulate in the liver following systemic delivery [16] , liver sections were also stained using H&E. There were no signs of tissue disarray or immune cell infiltration. RT-PCR was done to quantify the expression levels of collagen-1 and -3 in the hearts of the 3 groups of mice.…”

Progress of organoid platform in cardiovascular research

“…In addition to being a tool for introducing genetic variation into iPSCs, CRISPR/Cas9 can also effectively correct genetic variation in iPSCs [ 156 ]. Wang et al developed a protocol based on doxycycline-induced Cas9 transgene carried on piggyBac transposons to enable robust and efficient Cas9-directed genome editing so that parental lines can be rapidly designed to carry many individual mutations [ 157 ].…”