PCSK9
家族性高胆固醇血症
低密度脂蛋白受体
以兹提米比
遗传增强
基因组编辑
清脆的
载脂蛋白B
生物
微粒体甘油三酯转移蛋白
前蛋白转化酶
胆固醇转移蛋白
生物信息学
医学
癌症研究
脂蛋白
遗传学
胆固醇
基因
极低密度脂蛋白
内分泌学
作者
Negin Parsamanesh,Omid Kooshkaki,Haleh Siami,Raúl D. Santos,Tannaz Jamialahmadi,Amirhossein Sahebkar
标识
DOI:10.1016/j.drudis.2022.103470
摘要
Familial hypercholesterolemia (FH) is a common autosomal codominant hereditary illness marked by the heightened risk of early atherosclerotic cardiovascular disease and high blood levels of low-density lipoprotein cholesterol (LDL-C). FH patients can have homozygous or heterozygous variants. This condition has been linked to variations in the genes for the LDL receptor (LDLR), apolipoprotein B, proprotein convertase subtilisin/Kexin 9 (PCSK9), and LDLR adaptor protein 1. Drugs such as statins, ezetimibe, and PCSK9 inhibitors are currently widely available, allowing for the theoretical normalization of plasma LDL-C levels mostly in patients with heterozygous FH. However, homozygous FH patients usually have a poor response to traditional lipid-lowering therapy and may have a poor prognosis at a young age. LDL apheresis and novel pharmacological therapies such as microsomal transfer protein inhibitors or anti-angiopoietin-like protein 3 monoclonal antibodies are extremely expensive and unavailable in most regions of the world. Therefore, the unmet need persists for these patients. In this review, we discuss the numerous gene delivery, gene editing, and stem cell manipulation techniques used in this study to correct FH-causing LDLR gene variations in vitro, ex vivo, and in vivo. Finally, we looked at a variety of studies that corrected genetic defects that caused FH using the ground-breaking clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing technology.
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