Fixing a rare skin disease by correcting genes directly in the skin

In situ genome editing effectively restored transglutaminase 1 activity in human skin affected by a mutation causing autosomal recessive congenital ichthyosis.

• A common disease-causing mutation linked to autosomal recessive congenital ichthyosis was targeted for correction.
• The approach utilized a base editor combined with transient barrier modulation.
• Topical administration of mRNA-lipid nanoparticles was employed to facilitate the editing process.
• Restoration of clinically meaningful levels of transglutaminase 1 activity was achieved.

Simplified