Gene-editing therapies capable of significantly reducing the risk of cardiovascular disease may be on the horizon.
An article published May 25 in the New England Journal of Medicine, “In Vivo Base Editing of PCSK9 with VERVE-102 for Hypercholesterolemia” reports on the results of a phase 1 trial of a gene-editing infusion that causes a durable reduction in blood LDL cholesterol levels. High LDL cholesterol levels are associated with atherosclerotic cardiovascular disease, and current therapies designed to reduce their levels—such as statins—are not effective for all people. The safety results were promising: side-effects were at most mild to moderate and limited in duration.
The therapy is modeled on a naturally occurring gene variant. Some people carry a loss-of-function variant of the PCSK9 gene; they have markedly lower LDL cholesterol and lower rates of atherosclerotic cardiovascular disease across their lifetimes. The VERVE-102 treatment edits the patient’s genome to deactivate that protein. This is done by a one-time infusion containing a lipid nanoparticle whose exterior is marked in such a way that it will be preferentially taken up by liver cells. Once within the liver cells, the nanoparticle releases mRNA that is translated into a gene-editing protein, and guide RNA that ensures it acts only on the gene encoding PCSK9.
