Give a fat man a personal trainer and he’ll exercise for a day, give him a vaccine to heart disease and he’ll never have to exercise again. Scientists from the Harvard Stem Cell Institute and the University of Pennsylvania have actually found a way to permanently lower cholesterol levels in mice, and suggest that the approach may one day be used to prevent the risk of heart attack in humans.
The team used a form of genome editing to target the liver gene PCSK9, which was discovered in 2003 to be associated with regulating cholesterol — a mutation was found to raise incidences of heart attack and high cholesterol. Later on, another team, in Texas, found that three percent of the population have mutations in the gene that lower levels of low-density lipoprotein, or “bad” cholesterol by 15 to 28 percent, and led to as much as an 88 percent lower-than-average risk of heart attacks.
Essentially, it was a no-brainer for lead researcher Dr. Kiran Musunru, who said that nature had “already done the experiment,” in a press release. “They are protected from heart attack, and there are no known adverse consequences. So that led us to reason that if we could find a way to replicate this, we could significantly protect people from heart attack.”
So, on lab mice, the team used advanced genome editing technology, known as CRISPR-Cas9, to literally edit their DNA. The way the technology works can be broken down into two processes. First, scientists direct CRISPR, an RNA component, to a gene, so that it’s able to recognize its target. CRISPR then directs Cas9 to all matching sequences, where Cas9 is able to break the target gene. The broken cells are then able to repair themselves, but with errors. In turn, this “knocks out” the gene, making it virtually inoperative.
In humans and mice with high cholesterol, this would be good, because PCSK9 produces a protein that gets released into the bloodstream, and subsequently hinders the removal of cholesterol. By knocking out PCSK9, cholesterol would be removed more easily. So, with the help of a virus capable of entering cells, CRISPR-Cas9 was introduced to the livers of mice.
Musunru described the effect as “dramatic.” Within three to four days, “the majority of the PCSK9 gene copies in all of the liver cells were disrupted, knocked out. And what we hoped to see was much less of the protein product in the bloodstream, which is what we saw. The other consequence that we saw was a 35 to 40 percent reduction in cholesterol levels in these mice.”
In humans, that translates to as much as a 90 percent lower chance of heart attack.
If you’re sitting on your couch munching on your bacon-wrapped macaroni and cheese, expecting this vaccine to be your saving grace, you’re going to want to hope you don’t die of a heart attack for another 10 years. It would take at least that long to develop the “vaccine,” Musunru said.
One out of every four deaths in the U.S. is caused by heart disease, according to the Centers for Disease Control and Prevention. If this therapy were to be developed, Musunru estimates that it could “reduce the occurrence of heart attack by 30 percent, 50 percent, 90 percent.” Whichever one it is, there would no doubt be a reduction, and that’s a great thing.
Source: Ding Q, Strong A, Patel K, et al. Permanent Alteration of PCSK9 With In Vivo CRISPR-Cas9 Genome Editing. Circulation Research. 2014.