Obesity is a global health problem, and traditional weight loss therapies are often limited in their effectiveness and prone to accompanying adverse reactions In recent years, it has been found that the use of small interfering RNA (siRNA) technology to target regulation of obesity-related genes can effectively reduce body weight, opening up a new path for weight loss treatment. This review summarizes the mechanisms of action, delivery systems, and clinical progress of novel siRNA-based drugs, focusing on targeting genes such as transforming growth factor/cyclooxygenase, inhibin subunit beta E, and activin receptor-like kinase 7, which achieve precise targeting and enhanced therapeutic efficacy through their respective delivery systems. Meanwhile, this review also points out the drawbacks of existing drugs, including low delivery efficiency, risk of immune activation, and off-target effects.

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