Gene editing successfully lowers monkey cholesterol levels

In one of the first examples of gene-editing technology being effectively used to knock out the expression of a gene in non-human primates, researchers from the University of Pennsylvania have lowered the blood cholesterol in monkeys by disabling a single gene in the liver. The successful experiments pave the way for future human trials in five to 10 years. 

The target of the research is a well-known protein called PCSK9. A great deal of prior study has established that PCSK9 is a protein that inhibits the liver's ability to remove harmful cholesterol. Several drugs have been developed to inhibit the activity of PCSK9 but they are expensive and not consistently effective.

So some scientists have been investigating ways of genetically inhibiting PCSK9. This new study is the first to show effective reduction of PCSK9 in the liver through gene editing in a non-human primate. Rather than the more popular and recent CRISPR gene-editing technique, the study used a slightly older and different technique called meganuclease-based gene-editing.

Identified in the 1990s, meganucleases are enzymes that can be engineered for precision gene editing. In the case of this experiment the enzyme was engineered to inactivate the PCSK9 gene and was delivered to the liver by a harmless adeno-associated virus. The results were impressive, with the rhesus macaque monkeys showing between 45 and 84 percent reductions in PCSK9 levels, and associated cholesterol levels dropping by up to 60 percent. Analysis of liver tissue found effective mutations in 40 to 65 percent of PCSK9 genes.