Innovative gene therapy strategies for tackling obesity

Abstract Obesity is characterized by an excessive accumulation of body fat, resulting from an imbalance where biochemical processes related to fat synthesis outpace those responsible for energy expenditure. Genetic predisposition plays a significant role in the susceptibility to obesity. In this context, gene therapy presents a promising approach to address obesity as a global health concern by modulating gene expression to favor energy consumption and lipolysis, leading to fat reduction and the restoration of energy homeostasis. Recent advancements in gene therapy for obesity have leveraged novel vectors and delivery systems. Emerging approaches also use zinc finger proteins, small interfering RNAs, and self-cleaving ribozymes to modulate gene expression. Despite significant progress, several challenges remain in optimizing gene therapy for obesity. Key considerations include the selection of appropriate target genes, understanding long-term effects, ensuring the safety of gene transfer methods, conducting comprehensive preclinical studies, and developing strategies to mitigate potential side effects such as the random insertion of virus-borne transgenes and associated toxicity. Ongoing research and technological innovations will be essential in overcoming these challenges and translating gene therapy into a viable clinical solution for managing obesity.