In Vivo Gene Editing in Lipid and Atherosclerosis Research

Methods Mol Biol. 2022:2419:673-713. doi: 10.1007/978-1-0716-1924-7_42.

Abstract

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.

Keywords: AAV; Atherosclerosis; CRISPR/Cas9; Gene editing; Hypercholesterolemia; Ldlr; Lipid; Mouse model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis* / genetics
  • CRISPR-Cas Systems / genetics
  • Gene Editing / methods
  • Hypercholesterolemia* / genetics
  • Hyperlipidemias*
  • Mice