In this comprehensive review, the authors describe the current landscape of gene therapy and provide a valuable overview of advancements, challenges, and promising directions within this rapidly evolving field. They cover essential topics, from the development of novel vectors to molecular approaches tailored for treating inherited arrhythmias and cardiomyopathies. The review highlights significant pre-clinical in vivo studies and discusses critical strategies for refining genetic constructs, including innovations in promoter engineering and conditional gene expression systems.
The authors also address the main challenges in translating cardiac gene therapy to clinical settings, drawing lessons from previous trials on pre-clinical model reliability, vector dosage, delivery methods, and study design (PMID: 26803443). Additionally, the review highlights recent advancements, including the use of CRISPR/Cas9 technology for genome editing, which offers the potential for correcting genetic mutations associated with cardiomyopathies (PMID: 30195724). At the same time, the authors highlight the critical challenges of achieving precise and safe gene delivery in cardiac therapy, including potential immune responses (PMID: 19133809) and the need for precise gene editing to avoid off-target effects. Interestingly, they highlight research suggesting that even modest transduction of cardiomyocytes may provide protective benefits for certain inherited cardiac diseases, exploring the translational impact of this concept (PMID: 37965733).
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