Injectable gene therapy 'could prevent heart attacks'

A gene linked to cholesterol levels has been successfully edited in mice after they were given a single injection, thereby reducing their risk of heart disease, according to a study.

Researchers altered the DNA of a virus using a type of gene editing technology called CRISPR/Cas9. They then injected this virus into mice, where it altered the function of a liver gene called PCSK9. This then resulted in a 35-40 percent reduction of cholesterol in the blood, a similar reduction seen in people using cholesterol-lowering drugs.

Dr Kiran Musunuru, the senior author from Harvard Stem Cell Institute, said: 'The first question was whether we could get CRISPR/Cas9 into the liver, and once we got it into the liver, would it function properly, and it did'.

Describing the 'dramatic effect', he said: 'Within three to four days of delivering the system into the liver 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'.

If this technology is found to be effective and safe to use in humans, the researchers say that a similar reduction in cholesterol could reduce the risk of heart attacks by up to 90 percent.

'It's not too much of a leap to think that if it works as well in mice, it will work as well in humans', said Dr Musunuru. By developing an injection containing the genome editing technology, he hopes to 'make normal people like people born with the "good" mutations'.

Previous research had shown that around three percent of the population have a mutation in PCSK9 that leads to lower levels of low-density lipoprotein (LDL or 'bad cholesterol') and that they have a 47-88 percent reduced risk of heart attacks compared with the general population.

Dr Musunuru said: 'Our reasoning was that nature has already done the experiment; you have people who have won the genetic lottery'. He continued, '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'.

Although this research shows that a single injection to reduce cholesterol in humans is plausible, the genome-editing technique used is very new (as reported in BioNews 730) and more research is needed to assess its safety in humans.