A new ACC Scientific Statement outlines the rapidly evolving landscape of gene-editing therapies and their growing relevance to cardiovascular disease, offering clinicians an overview of both the promise and the challenges of this transformative technology.

Advances in genome sequencing have dramatically expanded access to genetic testing, improving availability while reducing cost. At the same time, technological innovations – most notably clustered regularly interspaced short palindromic repeats (CRISPR)–associated protein 9 (Cas9) – have enabled the precise and targeted editing of a patient's genome, raising the possibility of durable or even curative treatments for select cardiovascular conditions.

The ACC statement, published in JACC and chaired by Amrut V. Ambardekar, MD, FACC, provides a foundational overview of gene-editing therapies (GET) for practicing clinicians, beginning with the basic science that underpins these approaches. It highlights cardiovascular diseases that are currently most amenable to early application of gene editing, particularly monogenic disorders that can be modified through protein knockdown and whose pathogenic protein synthesis occurs in the liver. Examples include certain forms of hypercholesterolemia and amyloidosis, where early clinical experience has shown encouraging results.

A key focus of the statement is the delivery of gene-editing therapies. While safe, efficient, and targeted delivery has historically been a challenge, the development of lipid nanoparticles offers a promising nonviral strategy for cardiovascular diseases with hepatocyte-expressed treatment targets. Both viral and nonviral delivery methods are reviewed, along with their respective advantages and limitations.

The statement also addresses significant challenges that accompany rapid scientific progress. Many cardiovascular diseases have complex genetic underpinnings that are not amenable to a single gene-editing intervention. Additional hurdles include the need for prolonged safety follow-up in clinical trials, questions around comparative efficacy vs. existing therapies, economic implications of high-cost single-treatment cures, and concerns related to equitable access and long-term ethical considerations.

As gene-editing technology continues to expand, the statement emphasizes the central role of cardiovascular clinicians in ensuring these therapies are applied appropriately, ethically and equitably.

"Ultimately, GET may allow for a transition from reactive disease management to a model of durable, molecular disease prevention of disease," the authors conclude, "but this will only be possible through the application of scientific rigor, cautious optimism, and sustained ethical reflection."