New Frontiers in Gene Therapy Development for Heart Failure and Arrhythmias

Cardiovascular medicine is undergoing transformative change as gene therapy emerges as a promising approach to address heart failure and cardiac arrhythmias - two of the most prevalent and fatal conditions worldwide. Despite significant progress with pharmaceuticals, medical devices, and interventional procedures, many patients still face progressive symptoms, adverse events, and limited long-term outcomes. The resurgence of gene therapy in this context is propelled by advances in vector engineering, enabling improved tissue specificity, greater durability of therapeutic gene expression, and enhanced scalability in manufacturing. Current discourse centers around identifying appropriate therapeutic targets, optimizing delivery precision, minimizing immunogenicity, and identifying reliable biomarkers to measure clinical impact, with ongoing global efforts to translate early laboratory successes into tangible patient benefits.

Recent studies have highlighted notable progress in developing cardiac-specific viral and non-viral vectors, fine-tuning gene editing tools for inherited cardiomyopathies and arrhythmogenic disorders, and uncovering novel molecular targets capable of modifying disease trajectories. Nevertheless, the field faces persistent hurdles, such as achieving efficient and safe gene transfer to mature cardiomyocytes and electrophysiological conduction cells, targeting of heterogeneous populations of proliferating cells in the heart (e.g. fibroblasts, endothelial cells), controlling immune responses to both vector and transgene, managing dosing challenges, and establishing durable, long-term clinical efficacy. Many pivotal questions remain unanswered, particularly regarding the complexities of human disease heterogeneity and appropriately selecting endpoints in both early and late stage trials.

This Research Topic aims to bring together contributions that drive a deeper understanding of gene therapy’s potential and limitations for treating heart failure and arrhythmias. The main objectives include fostering innovative research on target selection, delivery systems, safety evaluation, measurement of therapeutic effects, and the integration of genomics and other omics approaches for patient stratification. The Research Topic also seeks to close gaps in translational science by encouraging the development of robust preclinical models and early phase clinical studies that address the pressing challenges hindering widespread clinical adoption.

To gather further insights into the expanding field of cardiovascular gene therapy, we welcome articles that focus on novel technologies and strategies, translational barriers, and future directions. Relevant themes include, but are not limited to:
• Identification and validation of molecular targets with disease-modifying potential
• Development and optimization of cardiac-targeted gene delivery vectors
• Strategies for gene replacement and gene silencing in cardiac disorders
• Genome editing approaches for inherited forms of heart failure and arrhythmia syndromes
• Preclinical and clinical evaluation of safety, efficacy, and biomarkers for gene therapy in heart failure and arrhythmias

Topic Editor TingTing Hong holds shares within a private startup company, TikkunLev Inc. The other Topic Editors declare no competing interests with regard to the Research Topic subject.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Community Case Study
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Community Case Study
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Policy Brief
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: Heart Failure, Gene Therapy, Precision Medicine, Cardiac Arrhythmias

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.