CRISPR (Clustered Regularly Interspaced Palindromic Repeat)/Cas9 System: A Revolutionary Disease-Modifying Technology.

Abstract

As clinicians, we are equipped with an ever-expanding armamentarium of drug and device therapies that have extended the lifespan of countless patients with cardiovascular disease. Nevertheless, it is likely that future therapies aimed at the root cause of disease, rather than secondary effects, will improve clinical outcomes in our patients yet further. Imagine if we could restore expression of a critical protein that is reduced as a consequence of remodeling associated with heart failure? Alternatively, what if a mutated gene in one of your patients with familial hypertrophic cardiomyopathy could actually be corrected such that they were essentially cured of their disease? Although these scenarios would have been inconceivable just a few years ago, molecular genetic tools now exist in principle to modify genomes and essentially fix a variety of diseases that affect the heart and blood vessels. To achieve this seemingly impossible objective, several research groups have swiftly repurposed a bacterial system for adaptive immunity, called the CRISPR (Clustered Regularly Interspaced Palindromic Repeat)/Cas9 System, as a revolutionary genome editing tool in mammalian tissues.1 For a genome modification technology to be translatable to human disease, it must be able to navigate the complex milieu of the human genome and precisely cut the DNA only at the …