Gene therapy in cardiac and vascular diseases: a review of approaches to treat genetic and common cardiovascular diseases with novel gene-based therapeutics

Journal article : Review

In the past decade, there has been substantive progress in gene therapy across disease indications. However, despite multiple gene therapies being approved for clinical use, none have a cardiovascular indication. Several reasons for this have inhibited or delayed progress in the cardiovascular field. First, developing cardiovascular gene therapeutics represents a substantial technical challenge, particularly relating to identifying and building effective delivery systems for therapeutic cargo that will be sufficient to gain meaningful efficacy with acceptable safety for the patient. Second, for genetic disease, gene editing therapy of pathogenic variants is at a relatively early stage of development. Third, since this is a field in development, the optimal design of clinical trials of cardiovascular gene therapies is also evolving and requires expert attention. Despite this, recent and current clinical trials are charting new ground, gaining valuable new patient-focused information that provides critical new learning and bench-to-bedside iterative development that has been so successful in other disease areas. While most clinical trials currently focus on cardiac gene therapy, vascular approaches are being developed, both genetic and common. We herein review the state-of-the-art in this rapidly progressing field of study. We consider gene therapy vector design, including transcriptional control, an area of incredible opportunity through engineering biology approaches to design, build, and test bespoke transcriptional units for expression of therapeutic cargo. Achieving progress in this exciting field will require close working between all stakeholders, including academic, clinical, industry, regulatory, and patient communities. Based on current progress, there is a 10-year horizon for bringing several cardiovascular gene therapies to licensing.

Authors: Musolino, PL; Rosser, SJ; Brittan, M; Newby, DE; Berry, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Oxford University Press
• Journal: Cardiovascular Research
• Volume: 121
• Issue: 12
• Pages: 1843-1855
• Publication date: 2025-08-25
• Acceptance date: 2025-05-22
• DOI: 10.1093/cvr/cvaf109
• EISSN: 1755-3245
• ISSN: 0008-6363
• Language: English
• Keywords: Gene therapy vectors; Cardiovascular disease; Gene therapy; Vascular; Regeneration; Heart failure; Gene editing
• Subtype: Review