体内基因编辑在脂质和动脉粥样硬化研究中的应用
In Vivo Gene Editing in Lipid and Atherosclerosis Research.
机构信息
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA.
Department of Medicine, Cardiology, University of California Los Angeles, Los Angeles, CA, USA.
出版信息
Methods Mol Biol. 2022;2419:673-713. doi: 10.1007/978-1-0716-1924-7_42.
The low-density lipoprotein receptor (Ldlr) and apolipoprotein E (Apoe) germline knockout (KO) models have provided fundamental insights in lipid and atherosclerosis research for decades. However, testing new candidate genes in these models requires extensive breeding, which is highly time and resource consuming. In this chapter, we provide methods for rapidly modeling hypercholesterolemia and atherosclerosis as well as testing new genes in adult mice through somatic gene editing. Adeno-associated viral (AAV) vectors are exploited to deliver the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 genome editing system (AAV-CRISPR) to the liver. This tool enables rapid and efficient editing of lipid- and atherosclerosis-related genes in the liver.
数十年来，载脂蛋白 B100（ApoB100）和前蛋白转化酶枯草溶菌素 9（PCSK9）的基因敲除（KO）模型为脂质和动脉粥样硬化研究提供了重要的见解。然而，在这些模型中测试新的候选基因需要广泛的繁殖，这需要大量的时间和资源。在本章中，我们提供了通过体细胞核移植技术快速建模高胆固醇血症和动脉粥样硬化以及在成年小鼠中测试新基因的方法。腺相关病毒（AAV）载体被用来将簇状规律间隔短回文重复序列（CRISPR）/Cas9 基因组编辑系统（AAV-CRISPR）递送到肝脏。该工具可以快速有效地编辑肝脏中与脂质和动脉粥样硬化相关的基因。
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