PCSK9的靶向基因治疗  

Gene therapy targeting PCSK9

作　　者：陈彦好 丁秋蓉 CHEN Yan-Hao;DING Qiu-Rong(CAS Key Laboratory of Nutrition,Metabolism and Food Safety,Shanghai Institute of Nutrition and Health,ChineseAcademy of Sciences,Shanghai 200031,China;University of Chinese Academy of Sciences,Beijing 100049,China)

机构地区：[1]中国科学院上海营养与健康研究所,中国科学院营养代谢与食品安全重点实验室,上海200031 [2]中国科学院大学,北京100049

出　　处：《生命科学》2022年第10期1264-1273,共10页Chinese Bulletin of Life Sciences

基　　金：国家自然科学基金项目(311971063);上海市优秀学术带头人(20XD1424500)。

摘　　要：心血管疾病是全球非传染性疾病致死的主要原因。降低血液低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)是预防和治疗动脉粥样硬化引起的冠状动脉疾病的主要手段。人类遗传学研究发现携带PCSK9功能缺失突变的个体血液LDL-C含量显著降低,对心血管疾病有明显的保护作用。这使得PCSK9成为基因编辑治疗以降低血液胆固醇的理想靶点。当前的研究证明在小鼠和非人灵长类动物中靶向敲除肝脏PCSK9可显著降低血液低密度脂蛋白胆固醇,展现该基因治疗策略的发展前景。该文介绍了PCSK9基因与心血管疾病的关系,并综述了基因组编辑技术的发展及其体内靶向PCSK9基因以降低LDL-C的研究进展。Cardiovascular diseases are the leading cause of deaths for non-communicable diseases globally.Lowering blood low-density lipoprotein cholesterol(LDL-C)has been demonstrated to be the primary target to prevent and treat coronary artery disease(CVD).Human genetic studies have revealed the protective effects of the PCSK9 loss-of-function mutations,in that individuals carrying these mutations have significantly lower LDL-C and are protected from CVD.These studies have provided PCSK9 as an ideal target for gene therapy in the treatment of hypercholesterolemia.In addition,targeted knockout of liver PCSK9 in mice and non-human primates have been demonstrated to be able to significantly reduce blood LDL-C.We here summarize the studies of PCSK9 in cardiovascular diseases,and the research progress of gene therapeutics targeting PCSK9 to reduce LDL-C.

关 键 词：基因治疗 PCSK9 基因编辑 CRISPR 低密度脂蛋白胆固醇 

分 类 号：R543[医药卫生—心血管疾病]