Editing the Failing Heart

• Wolfram ZIMMERMANN, University Medical Center Göttingen (Germany)

• Elizabeth MCNALLY, Northwestern University (USA)

Genome editing has the capacity to transform treatment for genetic and non-genetic cardiovascular disorders. Genetic testing is now making it routine to decipher mutations responsible for heart failure, arrhythmias, and other heritable cardiac disorders. Additionally, many common pathways implicated in heart failure development and progression have been uncovered as potential targets for genome editing. These mechanistic insights are now accompanied by progress in gene therapy, where delivery to the myocardium is possible. The goal of this Leducq Transatlantic Network of Excellence is to advance genome editing for the treatment of genetic and non-genetic heart failure towards first-in-patient studies. To apply gene editing to heart failure therapy, we assembled a dream team of basic, translational, and clinical scientists with synergistic expertise in identifying and defining the role of genetic mutations for heart disease, development of genome editing tools, human cell and tissue based heart failure modeling, gene therapy, and therapeutic genome editing. In addition to the highly complementary scientific background of the Network team, it is of pivotal importance for our Network goal that we have substantial experience in advancing basic discoveries to clinical applications. To facilitate translation, we will also engage regulatory agencies to develop a rational, ethical, and feasible path to gene editing of the failing heart. At the interface of unparalleled fundamental science as well as regulatory experience related to gene therapy medicinal products (GTMPs) and their translation into clinical applications, we will train the next generation of cardiovascular- and physician-scientists to deliver the promise of therapeutic genome editing in patients with heart failure.