Gabriella Kabboul Massaad
BME PhD Defense Presentation

Date: 2026-04-13
Time: 1:00 PM
Location / Meeting Link: HSRB I W106 (Rollins Auditorium) / https://emory.zoom.us/j/94926335918

Committee Members:
Rebecca D. Levit, MD (Advisor); Andrés J. García, PhD; Christopher B. Doering, PhD; Roger J. Hajjar, MD; Vahid Serpooshan, PhD


Title: Epicardial Hydrogel Delivery as a Platform for Cardiac Gene Therapeutics

Abstract:
Gene therapy has emerged as a promising strategy to address the molecular drivers underlying cardiovascular diseases. Despite progress in cardiac gene therapies, the use of adeno-associated viruses (AAVs) to deliver genes to the heart remains challenging due to inefficient myocardial gene uptake and immunological responses against AAV. The field has relied on increasing vector doses, resulting in dose-limiting toxicities and significant increases in cost of goods. Often overlooked, the delivery modality remains one of the biggest hurdles in cardiac gene therapy. Common administration routes result in poor cardiac gene uptake, systemic distribution to off-target organs, and immune-mediated responses against the vector. This project optimizes the delivery of AAV to the heart by engineering an epicardial hydrogel-based approach as a platform for enhanced cardiac gene therapy. In aim 1, synthetic hydrogels were engineered with tunable degradation kinetics for enhanced cardiac gene transfer. In aim 2, epicardial hydrogel delivery of AAV was compared to common routes of administration. In aim 3, the therapeutic efficacy of this epicardial hydrogel gene delivery platform was assessed as a proof-of-concept using follistatin-like 1 (FSTL1) as a pre-validated therapeutic gene. These studies show epicardial hydrogel delivery localizes AAV to the heart, reduces immune responses against the AAV, and yields cardiac therapeutic benefits. Overall, these findings support epicardial hydrogel delivery as a novel platform for cardiac gene therapeutics.