One Shot to Slash Cholesterol Levels: Scientists Use Epigenetic Editing to Combat Disease

Friday - March 8 2024, 13:23 UTC - 8 months ago

Scientists have successfully used epigenetic editing to reduce cholesterol levels in mice with just one shot. This method may be a safer alternative to traditional gene editing and has the potential to treat a range of diseases. The treatment lasted for nearly a year with no notable side effects, making it a potentially life-changing solution for individuals with high cholesterol.

With just one shot, scientists have slashed cholesterol levels in mice. The treatment lasted for at least half their lives. The shot may sound like gene editing, but it’s not. Instead, it relies on an up-and-coming method to control genetic activity—without directly changing DNA letters. Called "epigenetic editing," the technology targets the molecular machinery that switches genes on or off. Rather than rewriting genetic letters, which can cause unintended DNA swaps, epigenetic editing could potentially be safer as it leaves the cell’s original DNA sequences intact .

Scientists have long eyed the method as an alternative to CRISPR-based editing to control genetic activity. But so far, it has only been proven to work in cells grown in petri dishes. The new study, published this week in Nature, is a first proof of concept that the strategy also works inside the body. With just a single dose of the epigenetic editor infused into the bloodstream, the mice’s cholesterol levels rapidly dropped, and stayed low for nearly a year without notable side effects .

High cholesterol is a major risk factor for heart attacks, strokes, and blood vessel diseases. Millions of people rely on daily medication to keep its levels in check, often for years or even decades. A simple, long-lasting shot could be a potential life-changer. "The advantage here is that it’s a one-and-done treatment, instead of taking pills every day," study author Dr. Angelo Lombardo at the San Raffaele Scientific Institute told Nature .

Beyond cholesterol, the results showcase the potential of epigenetic editing as a powerful emerging tool to tackle a wide range of diseases, including cancer. To Dr. Henriette O’Geen at the University of California, Davis, it’s "the beginning of an era of getting away from cutting DNA" but still silencing genes that cause disease, paving the way for a new family of cures. Gene editing is revolutionizing biomedical science, with CRISPR-Cas9 leading the charge .

In the last few months, the United Kingdom and the US have both given the green light for a CRISPR-based gene editing therapy for sickle cell disease and beta thalassemia. These therapies work by replacing a dysfunctional gene with a healthy version. While effective, this requires cutting through DNA strands, which could lead to unexpected snips elsewhere in the genome. Some have even dubbed CRISPR-Cas9 a type of "genomic vandalism .

" Editing the epigenome sidesteps these problems. Literally meaning "above" the genome, epigenetics is the process by which cells control gene expression. It’s how cells form different identities—becoming, for example, brain, liver, or heart cells—during early development, even though all cells harbor the same genetic blueprint. Epigenetics also connects environmental factors—such as diet—with gene expression by flexibly controlling gene activity .

All this relies on myriad chemical "tags" that mark our genes. Each tag has a specific function. Methylation, for example, shuts a gene down. Like sticky notes, the tags can be easily added or removed with the help of their designated proteins—without mutating DNA sequences—making it an attractive target for gene editing. As a proof of concept, the researchers in Nature targeted a gene called "Pcsk9" that regulates cholesterol levels in mice .

They injected an epigenetic editor specific to this gene into the mice’s bloodstream, and, over the next two months, cholesterol levels gradually fell to about half of the original levels.