Mitchell McLennan described prenatal PCSK9 editing as a choice that future generations could inherit

Mitchell McLennan described prenatal PCSK9 editing as a choice that future generations could inherit

On September 11, in a reply to a post about a Nature paper, Mitchell McLennan shifted the discussion from an embryo experiment to a decision made by adults. Editing the PCSK9 gene could help a future child maintain lower levels of LDL, the particles that carry cholesterol in the blood, and the change could be passed on to their descendants.

In the full preprint, the authors describe PCSK9 as an established target for somatic cell editing. People with naturally occurring variants that reduce this gene’s activity have been observed to have lower LDL levels and a lower risk of coronary disease. In the embryo experiment, development was followed to the blastocyst stage, which precedes implantation in the uterine wall.

McLennan framed the issue this way:

“Editing PCSK9 before birth turns preventable adult disease into a choice about the genome of a future lineage.”

In an early trial of VERVE-102, a gene editor is delivered to the liver in adults to achieve lasting inactivation of PCSK9. With embryo editing, the decision is made before the child is born, and the change may be passed on to their descendants. The expected benefit of lower LDL levels would accrue to a future person; the choice rests with those acting today.

The September analysis of the same paper discussed complete PCSK9 editing alongside rare chromosomal damage at the target site and mosaic editing, in which cells within the same embryo carry different changes. Against this background, McLennan turns to institutions: they will need to explain why lower LDL levels over one person’s lifetime justify a heritable edit.