Development of a biological cardiac pacemaker using gene therapy in a preclinical model

Abstract

Objective: When cardiac atrioventricular nodal cells are damaged by disease, the implantation of a cardiac pacemaker becomes necessary. Several limitations and problems of artificial pacemakers have emerged during the past decades. In children and newborn babies with arrhythmia, initial size mismatch and their growth can pose a problem. Lead extraction and infections have additional risks. The aim of our study was the development of a biological cardiac pacemaker by in-vivo adenoviral transfection of ventricular cardiomyocytes in a large animal model with the gene encoding for Adenylate-Cyclase type VI (ACVI) in order to increase the intracellular concentration of cAMP and intrinsic rhythmic rate of the transfected cells, enabling ectopic pacing from the injection site.