Heart disease is a leading cause of death, but there is no current treatment that can regenerate heart muscle that is lost after heart attack or other cardiac injury. To overcome this, Tenaya has developed a gene therapy-based approach that targets non-muscle cells in the heart and converts them into working muscle cells, thereby restoring heart function. Proof-of-concept was previously demonstrated in cells derived from human hearts and in rodent and pig heart attack models using direct injection of the gene therapy into the heart during a surgical procedure. Currently, a dearth of effective and minimally invasive delivery options for gene or cell therapies for the heart creates an unmet clinical need in regenerative medicine that Tenaya has attempted to address through the design, creation, and testing of a cardiac injection catheter. This project aimed to test our cardiac reprogramming gene therapy in a pig model of heart attack using this injection catheter for delivery, which could ultimately be appropriate for clinical use in human patients. Surprisingly, while the results of this project showed that the injection catheter procedure was well-tolerated for delivery in pigs 4 weeks after a heart attack, we did not see an overall beneficial effect on heart function when this gene therapy was delivered by injection catheter, despite the benefit we observed in a prior pilot pig study using direct surgical injection. We hypothesize that the injection catheter-based delivery approach was inadequate for distributing the gene therapy to the damaged region of the heart where it could be most effective. We are analyzing treated pig hearts to determine the levels and localization of the gene therapy relative to the cardiac injury. If delivery was inadequate in this study, future efforts will be aimed at improving the route of administration or dosing regimen to reach the injured area and distribute adequate amounts of the gene therapy to the appropriate target cells.