Gene Editing Therapy in Cardiovascular Disease: 2026 ACC Scientific Statement: A Report of the American College of Cardiology.

Abstract

It is increasingly recognized that many cardiovascular diseases have a genetic basis. Advancements in genome sequencing have allowed for dramatically higher rates of genetic testing with improved availability at a reduced cost. Technologic innovations-catalyzed by clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9)-related approaches-have enabled the ability to edit an individual patient's genome in a precise and targeted manner. Delivery of these genetic interventions to desired cells specifically, safely, and efficiently has been a challenge, but the development of lipid nanoparticles offers a promising approach in cardiovascular diseases with hepatocyte-expressed treatment targets. Progress in genetic therapies have been exponential such that curative treatments for some cardiovascular diseases are imminent. Given such rapid advancement and the potential scope of impact, this scientific statement provides an overview of gene editing therapies for the practicing clinician. This includes descriptions of: 1) the basic science that supports gene editing therapy; 2) the cardiovascular diseases that are currently most amenable for initial application of gene editing-diseases that are typically monogenic, that are modifiable by knockdown of protein production, and whose protein synthesis errors occur in the liver (certain variants of hypercholesterolemia and amyloidosis); and 3) the inherent challenges of gene editing including the societal and ethical implications of high-cost, single-treatment cures. As gene editing technology in the treatment of cardiovascular diseases continues to expand and evolve, cardiovascular clinicians are key stakeholders in ensuring that these interventions are applied with the proper clinical indications and with guardrails to promote ethical and equitable treatment.