Editing monkeys’ genomes in their livers reduced the animals’ blood cholesterol levels, researchers reported yesterday (July 9) in Nature Biotechnology. The results suggest the technique could one day be used to treat certain heart disease patients who do not tolerate drugs designed to combat high cholesterol.
“It’s very nice work, one of the first demonstrations of gene-editing tools used with high efficiency in nonhuman primates,” Kiran Musunuru, a cardiologist and geneticist at the University of Pennsylvania who was not involved in the study, tells Science.
In the study, University of Pennsylvania gene therapy researcher James Wilson and his colleagues used a gene-editing tool called a meganuclease to target and inactivate the gene PCSK9, which produces a protein that prevents the body from removing LDL, the “bad” form of cholesterol, in the monkeys’ livers. The approach “worked incredibly well,” Wilson tells Science.
PCSK9 levels dropped by as much as 84 percent and LDL levels dipped as much as 60 percent in treated monkeys, the researchers report in the paper. The team now plans to work on preventing editing in sites other than the PCSK9 gene and any unwanted immune responses to the treatment so that it could be moved into clinical trials in humans to test its efficacy in patients with hypercholesterolemia, who don’t tolerate current cholesterol-lowering drugs that inhibit the PCSK9 protein.
“Most often these patients are treated with repeated injections of an antibody to PCSK9,” study coauthor Lili Wang says in a statement. “But, our study shows that with successful genome editing, patients who cannot tolerate inhibitor drugs might no longer need this type of repeat treatment.”
Many gene-editing tools are currently being tested, however, so “it’s too early to tell which of those approaches will translate” into people, MIT molecular geneticist Daniel Anderson tells Science.