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  • Review Article
  • Published:

Genome editing in cardiovascular diseases

Nature Reviews Cardiology volume 14, pages 11–20 (2017)Cite this article

Subjects

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

Abstract

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.

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Figure 1: Modes of repair of double-strand DNA breaks.
Figure 2: Use of CRISPR/Cas9 for genome editing.
Figure 3: Use of genome editing to rapidly generate isogenic hPSCs and differentiated cells.
Figure 4: Use of genome editing to rapidly generate knockout and knock-in mice.
Figure 5: Two approaches to therapeutic genome editing.

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  1. Department of Pediatrics, St. Christopher's Hospital for Children, 160 East Erie Avenue, Philadelphia, 19134, Pennsylvania, USA

    Alanna Strong

  2. Department of Medicine, and Department of Genetics, Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, 11–136 Smilow Center for Translational Research, 3400 Civic Center Boulevard, Building 421, Philadelphia, 19104, Pennsylvania, USA

    Alanna Strong & Kiran Musunuru

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Strong, A., Musunuru, K. Genome editing in cardiovascular diseases. Nat Rev Cardiol 14, 11–20 (2017). https://doi.org/10.1038/nrcardio.2016.139

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