Recent applications of CRISPR-Cas systems in animal models of human cardiovascular disease: Review article
Cardiovascular disease (CVD) causes more deaths, more years of life lost, and more years lived with disability than any other major category of disease worldwide. Gene editing technologies, including the CRISPR-Cas9 system and its offshoots, are increasingly applied in CVD animal research models to identify genetic drivers of disease processes and to develop and test targeted therapeutics. To explore the potential impact and limitations of using animal models for these applications, this review examines studies in which the creation of a CRISPR-Cas9 animal model has been used to find genetic drivers and develop therapies. Studies were identified using OVID Medline, searching the past 10 years of the primary literature across 4 CVD domains: congenital heart disease, hypertrophic cardiomyopathy, heart failure, and atherosclerosis. The studies illustrate the vast range of gene editing applications and the value of models that parallel human genetic pathophysiology for specific disease processes. Besides furthering anatomical, clinical, and natural historical understanding of CVD pathologies and providing biological substrates in the development of screening and diagnostic tools, animal models support foundational stages in the development of genetic therapeutics, from gene target identification to discovery and development of gene-editing therapy mechanisms and delivery vehicles, through conducting therapeutic trials to assess the risk-benefit ratio.