July 31st, 2014

What Does CRISPR’s Success Mean for Cholesterol Control?

CRISPR is a new technique for inactivating or editing specific genes. Developed in microorganisms, it also works in mammalian cells, including in vitro human cells and monkey embryos.

About 10 years ago, a gene was identified that is critical to production of the LDL cholesterol receptor (LDL-R): PCSK9. Naturally occurring human mutations that enhance the effect of this gene greatly reduce production of LDL-R in the liver, causing hypercholesterolemia. Conversely, mutations that impair expression of the gene greatly increase production of LDL-R, leading to LDL cholesterol levels that are 40% lower than normal (and coronary heart disease rates that are 90% lower than normal).

In a recent study, a multi-institutional team used CRISPR to knock out the PCSK9 gene in the livers of mice. A single injection of the virus carrying the CRISPR “machinery” to the mouse liver led to dramatic increases in LDL-R and decreases in plasma levels of LDL cholesterol. No adverse effects (such as inadvertently knocking out genes other than the target gene) were noted.

The study authors claim the result should be durable and that a single treatment might confer long-term cholesterol reduction, although they do not present proof of this. If this approach works safely in humans, the implications are obvious and enormous.

As clinicians, what is your response to this report?

This story was adapted from NEJM Journal Watch. You can find the original publication here.

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