Translational consistency of gene therapy strategies targeting inflammation in atrial fibrillation's management.

Atrial fibrillation (AF) is the most common cardiac rhythm disorder. AF risk factors include pathological ageing, hypertension, obesity, diabetes, and cardiac conditions such as myocardial infarction. Chronic inflammation is a major pathophysiological profile commonly observed in AF and its risk factors. Clinical and preclinical studies have suggested that increased expression of proinflammatory biomarkers such as the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, interleukin (IL)-1β, or IL6 is associated with the development and maintenance of cardiac arrhythmias including AF. Current anti-arrhythmic and anti-inflammatory treatments are non-optimal in AF management. In parallel, mounting evidence suggests that new biotechnologies including gene therapy approaches, might help to target specific genes to prevent or promote their expression and their associated protein activity. Applied to cardiac arrhythmias, gene therapy might help to restore normal functions of ion channels, optimal calcium (Ca2 +)-handling machinery, functional gap junctions, and efficient inflammatory signaling, known to be altered in AF. With an emphasis on the importance of gene therapy strategies targeting inflammation, this narrative review aims to: i) highlight the rationale and clinical relevance of gene therapy as an innovative strategy for the management of AF; ii) evaluate current knowledge regarding gene therapy vectors and delivery platforms applicable to cardiology and AF; iii) review emerging molecular targets explored in the context of AF gene therapy; and iv) identify promising gene-based therapeutic candidates, with a particular focus on inflammation-related pathways in AF.