From Bench to Bedside: Current Developments in RNA-Based Therapies for Treatment of Hyperlipidemia

Review From Bench to Bedside: Current Developments in RNA-Based Therapies for Treatment of Hyperlipidemia Yufei Zhou and Chen Chen * Division of Cardiology and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. * Correspondence: chenchen@tjh.tjmu.edu.cn; Tel. & Fax: 86-27-6937-8422.     Received: 7 October 2022 Accepted: 1 November 2022 Published: 21 December 2022   Abstract: Hyperlipidemia is one of the conditions that constitute metabolic disorder and it is a common public health problem. The condition is characterized by increased levels of cholesterol, triglycerides and/or lipoproteins; it is a recognized as a risk factor for the onset of many diseases such as type 2 diabetes, non-alcoholic fatty liver disease, and cardiovascular disease. Up to now, the primary drugs for treating hyperlipidemia are statins and monoclonal antibody drugs against proprotein convertase subtilisin/kexin type 9 (PCSK9). The main limitation of statins for long-term use is intolerable side effects. Evolocumab and Alirocumab, two monoclonal antibodies against PCSK9, can effectively decrease the level of low-density lipoprotein cholesterol (LDL-C) in patients with statin intolerance and familial hypercholesterolemia, while causing fewer side effects. However, due to its short half-life and high costs, these monoclonal antibody treatments might result in patients’ non-compliance with medication and considerable economic burden on patients. Given that RNA plays a key role in gene regulation, RNA-based therapeutics have become powerful blueprints for designing new anti-hyperlipidemia drugs. Here, we summarized RNA-based therapeutic strategies and the current clinical trials for RNA drugs in hyperlipidemia treatment.