速递｜圣因生物治疗肥胖症siRNA药物，国内获批临床！

Core Viewpoint - The article discusses the urgent need for new mechanisms in obesity treatment, highlighting the development of a novel siRNA candidate drug, SGB-7342, by Shengyin Biotech, which targets INHBE for obesity treatment [4][11]. Group 1: Obesity as a Public Health Challenge - Obesity is a chronic metabolic disease characterized by abnormal or excessive fat accumulation, significantly increasing the risk of cardiovascular diseases, type 2 diabetes, and various cancers [5]. - The global population of obese individuals has surpassed 1 billion and is expected to reach approximately 1.37 billion by 2035; in China, there are about 180 million adult obesity patients [6]. Group 2: Current Treatment Limitations - Current mainstream obesity treatments primarily involve GLP-1 receptor agonists, which suppress appetite through the central nervous system but have drawbacks such as gastrointestinal side effects, muscle loss risk, and weight regain after discontinuation [7]. Group 3: RNAi Therapy as a New Approach - RNAi therapy offers a differentiated treatment strategy that does not rely on central appetite regulation, aiming to regulate fat metabolism at the source by targeting key genes involved in fat breakdown and storage [8]. - This approach is expected to selectively reduce fat while preserving muscle mass and improving overall metabolic health, potentially lowering the risk of adverse effects associated with traditional therapies [8]. Group 4: INHBE as a Novel Metabolic Target - The INHBE gene, primarily expressed in the liver, encodes the secreted protein Activin E, which regulates fat breakdown and energy storage by binding to the ALK7 receptor in adipose tissue [9]. - Genetic studies indicate that individuals with INHBE loss-of-function mutations exhibit favorable metabolic traits, providing a biological basis for targeting INHBE in drug development [9]. Group 5: SGB-7342 Candidate Drug - SGB-7342 is a siRNA candidate drug targeting INHBE for obesity treatment, utilizing Shengyin Biotech's proprietary GalNAc conjugation delivery technology for precise liver targeting [10]. - The mechanism involves silencing INHBE mRNA in the liver to lower Activin E protein levels, promoting fat breakdown without inducing muscle loss, thereby improving metabolic disorders and insulin resistance [10]. - Preclinical studies show that SGB-7342 leads to significant weight loss and improved body composition while maintaining muscle mass, demonstrating good safety and tolerability [10]. Group 6: Future Outlook - Obesity is recognized as a complex systemic metabolic disease rather than merely a weight issue, with significant unmet clinical needs in the global obesity treatment landscape [11]. - RNAi therapy, with its novel mechanism directly targeting metabolic pathways, is expected to offer differentiated advantages in selective fat reduction, muscle protection, and long-lasting treatment [11].