Recently, a group of researchers conducted a groundbreaking experiment in which they successfully edited a primate’s genome to reduce cholesterol levels, potentially creating a new heart disease treatment. In their work recently published in Nature, a group of researchers targeted the PCSK9 gene, which codes for a protein that hinders removal of the low-density lipoprotein (LDL) cholesterol. Elevated LDL concentrations have been extensively studied in their relation to increased risks of cardiovascular disease, dubbing the compound the “bad” cholesterol.
1st genome editing for clinically meaningful gene expression in primates: inactivating PCSK9 –> low LDL cholesterol, sustained via 1-shothttps://t.co/j8raHDbAp6 @NatureBiotech pic.twitter.com/WXrY6FiFLi
— Eric Topol (@EricTopol) July 9, 2018
Initially, the team used an injection containing adeno-associated viruses (AAV), a widely used tool in gene therapy that can cut a gene and disabling it without causing virulent effects, and CRISPR, a popular genomic editor. This technique worked with mice, but not in rhesus macaques. Researchers then used the AAV with meganuclease, another gene editing tool, and had great success.
Researcher James Wilson reports that 4 months after treatment, 64% of the liver cells contained knocked-out PCSK9 gene in all six of the macaques that received treatment. PCSK9 protein and LDL cholesterol levels were found to fall by 84% 60%, respectively. The genetically altered cells stopped synthesizing meganuclease for reasons the researchers were unsure of. Had the cells continued to create the enzyme, however, it would make undesirable edits to the genome.
The meganuclease did yield an immune response due to elevated liver enzyme levels, however researchers were not surprised by this being that they were introducing a foreign protein to a mammal. It was also found to make cuts at some sites other than the PCSK9 site, a mistake that could potentially give rise to cancer. Regardless, Wilson believes that with work, the drug could be efficient in treating patients with high cholesterol who cannot take PCSK9 protein blockers.