CRISPR Treatment Lowered Cholesterol in Monkeys by 60 Percent

More than one in three western adults have high cholesterol, which can lead to serious health problems like heart disease and stroke. The best remedies we have right now are cholesterol-lowering drugs called statins, a diet rich in vegetables and low in fat, and good old-fashioned exercise. But in the future, there may be another way to reduce our cholesterol levels.

Because of the health problems associated with too much of it, we often think of cholesterol as a bad thing. But it’s actually essential to multiple functions in the body; cholesterol helps form the protective layer of the cell membrane, and helps the body make bile, vitamin D, and certain hormones. The two main types of cholesterol are LDL and HDL, or low-density lipoprotein and high-density lipoprotein.

A gene called PCSK9 is in charge of making a protein that regulates cholesterol. Mainly active in the liver, the protein doesn’t break down cholesterol directly, but breaks down the receptors on the surface of liver cells that bind to LDL particles.

Too much PCSK9 protein means more breakdown of receptors, which means fewer receptors standing ready on cells to do their job of removing cholesterol from the blood.
Conversely, if there’s less PCSK9 floating around in the blood, more LDL receptors will bind to cells, and more cholesterol will get cleaned out of the system.

In the study, the team manipulated the PCSK9 gene by changing a single nucleotide from A to G at a specific location. The adenine base editors, which don’t cut the DNA strand like the original CRISPR-Cas9 tool does, were encoded in mRNA then injected into the monkeys using lipid nanoparticles .

Blocking the PCSK9 protein isn’t a new idea. The FDA approved the first two PCSK9 inhibitors—alternatives to statins—in 2015. The drugs need to be injected into recipients every two to four weeks. Other therapies that target PCSK9 also require frequent dosing, from every six months down to every day.
A study similar to this one was done in 2020, also led by Verve Therapeutics; it showed a 59 percent decrease in monkeys’ LDL cholesterol after 2 weeks, but didn’t report on longer-term effects.

Though many believe there will never be a true substitute for a healthy lifestyle, this also isn’t the first study that suggests we might be able to science our way out of some big health problems one day. Scientists are working on an “exercise pill” that would be pretty much what it sounds like: you’d take a pill that would cause your body to mimic the chain of events that occurs when you exercise, reaping the same health benefits without having to hit the treadmill or the weight room. Similarly, last year researchers used gene therapy to increase muscle mass in mice, with much success; the muscle mass and strength level of the treated mice more than doubled in four months, while the mice ate a diet high in fat and did minimal exercise.