In vivo genome and base editing of a human PCSK9 knock-in hypercholesterolemic mouse model.

ABSTRACT:

Background

Plasma concentration of low-density lipoprotein (LDL) cholesterol is a well-established risk factor for cardiovascular disease. Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), which regulates cholesterol homeostasis, has recently emerged as an approach to reduce cholesterol levels. The development of humanized animal models is an important step to validate and study human drug targets, and use of genome and base editing has been proposed as a mean to target disease alleles.

Results

To address the lack of validated models to test the safety and efficacy of techniques to target human PCSK9, we generated a liver-specific human PCSK9 knock-in mouse model (hPCSK9-KI). We showed that plasma concentrations of total cholesterol were higher in hPCSK9-K

SUBMITTER: Carreras A 

PROVIDER: S-EPMC6334452 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature