The results of the preclinical study were published in Molecular Therapy and conducted by researchers at the University of Pennsylvania (Penn) Perelman School of Medicine, the Penn Gene Therapy Program, and the Penn Orphan Disease Center.

In an effort to remove excess low-density lipoprotein in the liver, the researchers delivered a gene encoding an Arcus nuclease by adeno-associated virus (AAV) to inactivate the PCSK9 gene and inhibit protein expression. The Arcus genome editing technology uses sequence-specific nucleases that are designed to either insert (knock-in), remove (knock-out), or repair DNA of living cells and organisms. It is based on a naturally occurring genome editing enzyme, I-CreI, that evolved in the algae Chlamydomonas reinhardtii.

The nonhuman primates were monitored for more than three years and have shown sustained reduction in low-density lipoprotein cholesterol levels while maintaining stable gene editing without any obvious adverse effects. After a one-time vector administration more than three years ago, nonhuman primates treated with Arcus have experienced a stable reduction of up to 85% in PCSK9 protein levels and a 56% reduction of low-density lipoprotein cholesterol levels.