Researchers have successfully used genome editing to reduce blood cholesterol in living monkeys.
The group, led by Professor James Wilson at the University of Pennsylvania in Philadelphia, used genome editing to reduce levels of an enzyme named PCSK9 in the liver of Rhesus macaques. PCSK9 boosts the level of low-density lipoproteins (LDLs) in the bloodstream, which in high levels contribute to heart disease. The genome editing treatment reduced LDL levels in the monkeys' blood by 60 percent, persisting over the course of a year.
Dr Lili Wang at the University of Pennsylvania, first author on the study, said: 'Most often these patients are treated with repeated injections of an antibody to PCSK9, but our study shows that with successful genome editing, patients who cannot tolerate inhibitor drugs might no longer need this type of repeat treatment.'
The approach of altering levels of PCSK9 in the blood to control cholesterol is not new, but using genome editing to do so is. The paper represents 'one of the first demonstrations of gene-editing tools used with high efficiency in nonhuman primates' Professor Kiran Musunuru of the Harvard Stem Cell Institute, Massachusetts, a geneticist who was not involved in the work, told Science.
CRISPR-based genome editing techniques are considered cutting edge, but the team actually used an older tool - a meganuclease, to achieve their edits. This is because they found CRISPR to be less effective in this biological context.
The paper also addressed safety concerns and immune toxicity considerations. The authors stated that immune toxicity was 'not unexpected' given the introduction of a foreign protein into the liver. Indeed, a certain amount was observed – levels of liver enzymes in the monkeys rose. They suggest 'further studies in non-human primates may be useful in characterising and mitigating immune toxicity'.
There were also a number of off-target effects of the meganuclease, although whether they have had any negative effect is not clear, as the animals were only observed for a year. The authors are hopeful that with further understanding of the risks and benefits involved, the techniques developed here may represent a novel route to treating high cholesterol.
The study was published in Nature Biotechnology.