Researchers Fix Cholesterol in Monkeys Through CRISPR Gene Editing

The scientists developed a one-time gene therapy that reduced monkeys' LDL cholesterol levels by 60 percent in just one week.
Loukia Papadopoulos

According to the CDC, heart disease is the leading cause of death for men, women, and people of most racial and ethnic groups in the United States. It is estimated that one person dies every 36 seconds in the United States from cardiovascular disease.

Now, scientists have now successfully used CRISPR base editors to turn off the gene that produces low-density lipoprotein (LDL) cholesterol in monkeys. The research, if replicable on humans, could help eradicate a major cause of heart disease.

The work was a collaboration between researchers from the University of Pennsylvania and the private company Verve Therapeutics. Together the researchers developed a one-time gene therapy that reduced monkeys' LDL cholesterol levels by 60 percent in just one week.

"Here we demonstrate that CRISPR base editors that are delivered in vivo using lipid nanoparticles can efficiently and precisely modify disease-related genes in living cynomolgus monkeys (Macaca fascicularis)," wrote the researchers in their study published in the journal Nature.

"We observed a near-complete knockdown of PCSK9 in the liver after a single infusion of lipid nanoparticles, with concomitant reductions in blood levels of PCSK9 and low-density lipoprotein cholesterol of approximately 90% and about 60%, respectively; all of these changes remained stable for at least 8 months after a single-dose treatment."

When overactive, the gene PCSK9 will produce too much of a protein of the same name that interferes with the body’s ability to clear LDL cholesterol out of the circulatory system. LDL is the bad kind of cholesterol and results in a greater risk of cardiovascular disease. 

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Although we are still a long way from human trials, the fact that these results were achieved in monkeys — which are primates — is quite promising.  "In addition to supporting a ‘once-and-done’ approach to the reduction of low-density lipoprotein cholesterol and the treatment of atherosclerotic cardiovascular disease, our results provide a proof-of-concept for how CRISPR base editors can be productively applied to make precise single-nucleotide changes in therapeutic target genes in the liver, and potentially in other organs," conclude the researchers.

Could a cure for cholesterol be on the horizon?