Eric Lander and colleagues consider the ethical and safety concerns that distinguish heritable (germline) from non-heritable (somatic) genome editing (Nature 567, 165–168; 2019). However, unintended germline modification could result from well-intentioned somatic-genome-editing procedures. We therefore also need to consider how such risks might be mitigated and managed.

For non-heritable genome editing, somatic cells from a consenting adult are edited in the laboratory and then re-implanted. This ex vivo approach is unlikely to correct many genetic conditions. Deactivated viruses, liposomes and nanoparticles are therefore being tested as vehicles by which to convey the genome-editing machinery to faulty cells in vivo.

Restricting delivery to specific organs — the brain, for example — might work in some cases. However, treating disorders such as muscular dystrophies could involve exposing large parts of the periphery, including the gonads, to delivery vectors. It is therefore crucial to establish an acceptable level of risk to the germ line that allows in vivo somatic editing to proceed.