Permanent alteration of PCSK9 with in vivo CRISPR-Cas9 genome editing.

ABSTRACT:

Rationale

Individuals with naturally occurring loss-of-function proprotein convertase subtilisin/kexin type 9 (PCSK9) mutations experience reduced low-density lipoprotein cholesterol levels and protection against cardiovascular disease.

Objective

The goal of this study was to assess whether genome editing using a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system can efficiently introduce loss-of-function mutations into the endogenous PCSK9 gene in vivo.

Methods and results

We used adenovirus to express CRISPR-associated 9 and a CRISPR guide RNA targeting Pcsk9 in mouse liver, where the gene is specifically expressed. We found that <3 to 4 days of administration of the virus, the mutagenesis rate of Pcsk9 in the liver was as hi

SUBMITTER: Ding Q 

PROVIDER: S-EPMC4134749 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature