CRISPR Modeling and Correction of Cardiovascular Disease.
Ning LiuEric N OlsonPublished in: Circulation research (2022)
Cardiovascular disease remains the leading cause of morbidity and mortality in the developed world. In recent decades, extraordinary effort has been devoted to defining the molecular and pathophysiological characteristics of the diseased heart and vasculature. Mouse models have been especially powerful in illuminating the complex signaling pathways, genetic and epigenetic regulatory circuits, and multicellular interactions that underlie cardiovascular disease. The advent of CRISPR genome editing has ushered in a new era of cardiovascular research and possibilities for genetic correction of disease. Next-generation sequencing technologies have greatly accelerated the identification of disease-causing mutations, and advances in gene editing have enabled the rapid modeling of these mutations in mice and patient-derived induced pluripotent stem cells. The ability to correct the genetic drivers of cardiovascular disease through delivery of gene editing components in vivo, while still facing challenges, represents an exciting therapeutic frontier. In this review, we provide an overview of cardiovascular disease mechanisms and the potential applications of CRISPR genome editing for disease modeling and correction. We also discuss the extent to which mice can faithfully model cardiovascular disease and the opportunities and challenges that lie ahead.
Keyphrases
- genome editing
- cardiovascular disease
- crispr cas
- genome wide
- type diabetes
- cardiovascular risk factors
- cardiovascular events
- copy number
- induced pluripotent stem cells
- gene expression
- mouse model
- risk assessment
- transcription factor
- coronary artery disease
- adipose tissue
- climate change
- metabolic syndrome
- atrial fibrillation
- human health
- cell proliferation