Gene-editing reduces triglycerides, cholesterol by up to 50 percent

Using a variation of CRISPR gene editing may be a potential strategy for mimicking the protective effects of a genetic mutation linked to lower cholesterol levels and heart disease risks, according to new mouse research from the Perelman School of Medicine at the University of Pennsylvania. 

People with naturally occurring mutations that cause a loss of function in the gene for ANGPTL3 have reduced blood triglycerides, LDL cholesterol, and risk of coronary heart disease, with no apparent detrimental consequences to their health. This makes the ANGPTL3 protein an attractive target for new heart disease drugs. Earlier studies at Penn found that single copies of inactivating mutations in ANGPTL3 are found in about one in every 250 people of European heritage; however, people with mutations in both copies of the gene are more rare.

A team led by Kiran Musunuru, MD, PhD, MPH, an associate professor of Cardiovascular Medicine, assessed in a mouse model whether base editing - a variation of CRISPR genome editing that does not require breaks in the double-strand of DNA - might be used in humans one day to introduce mutations into ANGPTL3 to reduce blood lipid levels.

"This proof-of-principle study showed that base-editing of ANGPTL3 is a potential way to permanently treat patients with harmful blood lipid levels," Musunuru said. "It would be especially useful in patients with a rare condition called homozygous familial hypercholesterolemia, which causes sky-high cholesterol levels and dramatically increased risk of heart attack. They are very difficult to treat with today's medications, and a one-time CRISPR 'vaccination' might be ready to use in these patients within five years."