Why the study?
Existing PCSK9 therapies require repeated subcutaneous injections to maintain LDL-C reduction, whereas CRISPR gene editing may offer a lifelong therapeutic approach.
CRISPR gene editing targeting PCSK9 represents a promising future therapeutic strategy for lifelong LDL-C reduction in atherosclerotic cardiovascular disease.
May identify metabolite shifts with PCSK9 inhibition; leaves open clinical relevance for ASCVD risk.
Elevated circulating concentrations of low-density lipoprotein cholesterol (LDL-C) have been conclusively demonstrated in epidemiological and intervention studies to be causally associated with the development of atherosclerotic cardiovascular disease. Enormous advances in LDL-C reduction have been achieved through the use of statins, and in recent years, through drugs targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of the hepatic LDL-receptor. Existing approaches to PCSK9 targeting have used monoclonal antibodies or RNA interference. Although these approaches do not require daily dosing, as statins do, repeated subcutaneous injections are nevertheless necessary to maintain effectiveness over time. Recent experimental studies suggest that clustered regularly interspaced short palindromic repeats (CRISPR) gene-editing targeted at PCSK9 may represent a promising tool to achieve the elusive goal of a 'fire and forget' lifelong approach to LDL-C reduction. This paper will provide an overview of CRISPR technology, with a particular focus on recent studies with relevance to its potential use in atherosclerotic cardiovascular disease.
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Walker et al. (2021) studied this question.
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