Genome editing in cardiovascular diseases

Key Points Genome-editing technology has advanced considerably since 2013 Genome-editing tools, particularly ZFNs, TALENs, and CRISPR/Cas9, are being rapidly assimilated into cardiovascular disease research Genome-editing tools facilitate the creation of novel cellular and animal disease models, the purification or labelling of cell types, the study of transcriptional regulation, and modulation of gene expression Genome-editing tools not only allow for the evaluation of traditional therapeutic agents, but are also a new therapeutic modality to prevent and treat diseases Despite considerable progress, genome-editing tools still have substantial shortcomings that need to be addressed Genome editing is being rapidly adopted into all fields of biomedical research, including the cardiovascular field. In this Review, Strong and Musunuru discuss the applications of genome-editing technology, including zinc finger nucleases, TALENs, and CRISPR/Cas9 systems, throughout cardiovascular disease research, their current limitations, and the prospect of in vivo genome-editing therapies in the future. Genome-editing tools, which include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) systems, have emerged as an invaluable technology to achieve somatic and germline genomic manipulation in cells and model organisms for multiple applications, including the creation of knockout alleles, introducing desired mutations into genomic DNA, and inserting novel transgenes. Genome editing is being rapidly adopted into all fields of biomedical research, including the cardiovascular field, where it has facilitated a greater understanding of lipid metabolism, electrophysiology, cardiomyopathies, and other cardiovascular disorders, has helped to create a wider variety of cellular and animal models, and has opened the door to a new class of therapies. In this Review, we discuss the applications of genome-editing technology throughout cardiovascular disease research and the prospect of in vivo genome-editing therapies in the future. We also describe some of the existing limitations of genome-editing tools that will need to be addressed if cardiovascular genome editing is to achieve its full scientific and therapeutic potential.